Elucidating the clinical and genetic spectrum of inositol polyphosphate phosphatase INPP4A-related neurodevelopmental disorder.

PURPOSE: Biallelic INPP4A variants have recently been associated with severe neurodevelopmental disease in single case reports. Here, we expand and elucidate the clinical-genetic spectrum and provide a pathomechanistic explanation for genotype-phenotype correlations. METHODS: Clinical and genomic investigations of 30 individuals were undertaken alongside molecular and in silico modelling and translation reinitiation studies. RESULTS: We characterize a clinically variable disorder with cardinal features including global developmental delay, severe-profound intellectual disability, microcephaly, limb weakness, cerebellar signs and short stature. A more severe presentation associated with biallelic INPP4A variants downstream of exon 4 has additional features of (ponto)cerebellar hypoplasia, reduced cerebral volume, peripheral spasticity, contractures, intractable seizures and cortical visual impairment. Our studies identify the likely pathomechanism of this genotype-phenotype correlation entailing translational reinitiation in exon 4 resulting in an N-terminal truncated INPP4A protein retaining partial functionality, associated with less severe disease. We also identified identical reinitiation site conservation in Inpp4a-/- mouse models displaying similar genotype-phenotype correlation. Additionally, we show fibroblasts from a single affected individual exhibit disrupted endocytic trafficking pathways, indicating the potential biological basis of the condition. CONCLUSION: Our studies comprehensively characterise INPP4A-related neurodevelopmental disorder and suggest genotype-specific clinical assessment guidelines. We propose the potential mechanistic basis of observed genotype-phenotype correlations entails exon 4 translation reinitiation.

Colorectal cancer-related resource utilization and healthcare costs in Saudi Arabia.

Background: Recently, there has been an increase in the incidence of colorectal cancer in Saudi Arabia. Although numerous studies worldwide have investigated the economic burden of colorectal cancer the information specific to Saudi Arabia remains limited. While advanced cancer treatments offer substantial benefits, they they also come with substantial financial challenges. Objective: This study aimed to estimate the economic burden of colorectal cancer and identify the primary cost drivers. Method: This retrospective, single-center cost of illness study examined all patients with colorectal cancer from January 2017 to December 2020. This study used a micro-costing, bottom-up approach to estimate healthcare resource utilization and direct medical costs associated with colorectal cancer. Result: The study included 326 patients with colorectal cancer. The total direct medical cost for all patients were $19 million, with an annual cost per patient of $58,384. Medication costs were the primary driver of healthcare spending (45%) of the total cost, followed by surgical costs (27%). This study explained cost associated with colorectal cancer, which represents a significant cost to the Saudi healthcare budget. The expected growth and aging of the population and availability of costly treatments may lead to an increase in costs. These findings are valuable for healthcare policymakers seeking to comprehend the economic challenges posed by colorectal cancer.

Standardized reporting of complications of epilepsy surgery and invasive monitoring: A single-center retrospective study.

OBJECTIVE: Monitoring adverse effects related to epilepsy surgery is essential for quality control and for counseling patients prior to the procedure. The aim of this study was to analyze the rates of complications related to epilepsy surgery following invasive monitoring and to classify them according to the recently proposed protocol by the E-pilepsy consortium. METHODS: This is a retrospective study of collected data extracted from our routinely updated epilepsy surgery database which consisted of 173 surgical procedures: 89 surgeries for insertion of subdural grids, strips, and/or depth electrodes, and 84 resective surgeries. According to the protocol, complications were defined as unexpected postoperative adverse events and were stratified into transient (lasting less than 6 months) and permanent deficits (lasting 6 months or longer). In addition, we reported patients with postoperative psychiatric disturbances and calculated the rates of transient and permanent postoperative sequelae which were defined as expected postoperative deficits deemed inherent to the surgical procedure. RESULTS: Six potentially life-threatening complications requiring acceleration of the planned resective surgery occurred during invasive monitoring. Following resective surgery, 12 transient sequelae (8 motor deficits, three language deficits, and one transient dyscalculia) and 10 permanent sequelae (5 mild memory disturbances, four visual field cuts, and one contralateral dysesthesia) occurred. In addition, 7 patients experienced transient motor complications. Four permanent postoperative neurological complications (4.8%) occurred: motor deficits in three patients and a partial peripheral facial palsy in one. Finally, five patients developed de novo psychiatric disturbances (transient in four and permanent in one). CONCLUSIONS: This is the first study to classify complications of epilepsy surgery according to the E-pilepsy consortium protocol. Our findings demonstrate that epilepsy surgery following invasive monitoring is safe and associated with low morbidity when performed in specialized centers. Monitoring these complications according to a unified definition and using a multidimensional protocol will allow for a direct comparison across epilepsy surgery centers, will provide the epileptologists and surgeons with objective percentages to share with their patients and will help in identifying risk factors and improving the safety of epilepsy surgery.

Outcomes following Craniosynostosis Surgery at a Tertiary Care Center in the Middle East.

BACKGROUND: Despite advancements in craniosynostosis surgery, open surgical approaches remain crucial for the management of infants >6 months of age and in those with complex synostosis. The clinical features of craniosynostosis remain poorly characterized in the Middle East. This study sought to assess the clinical features and outcomes of infants undergoing craniosynostosis surgery at a tertiary care center in Lebanon. METHODS: A retrospective review was performed of all patients who underwent craniosynostosis surgery from December 2006 to December 2018 at the American University of Beirut Medical Center, Lebanon. Clinicodemographic characteristics, complications, and recurrence outcomes were recorded and evaluated using descriptive statistics. RESULTS: Thirty-five infants met the inclusion criteria, with a mean age of 9.0 ± 4.0 months. The most common site of suture involvement was metopic (28.6%), followed by unilateral coronal (25.7%), sagittal (20.0%), bicoronal (8.6%), and multiple sites (17.1%). Five patients (14.3%) had syndromic synostosis. Median estimated blood loss was 200 mL, and median volume of transfused packed red blood cells was 180 mL. Two patients (5.7%) experienced postoperative complications, including postoperative blood transfusion (n = 1)and wire protrusion requiring removal (n = 1). Three patients (8.6%) required reoperation: 2 (5.7%) for resynostosis and 1 for traumatic fracture repair. Caregivers of all patients reported high satisfaction with cosmetic outcomes 4 weeks postoperatively. CONCLUSIONS: With appropriate perioperative precautions, open craniosynostosis surgery can be performed with minimal complications, low recurrence rates, and satisfactory cosmetic outcomes. Additional population-level data are needed to better characterize craniosynostosis patterns and outcomes in the Middle East.

Simultaneous sampling of both cingulate gyri using a single interhemispheric depth electrode: A technical note.

Background: Simultaneous sampling of the cingulate gyri through a single depth electrode inserted underneath the falx cerebri is clinically useful in certain cases of drug-resistant epilepsy. However, the frequency at which each region of the cingulate gyri - namely, anterior, middle, and posterior - can be simultaneously sampled with a single electrode remains uncertain. Methods: We assessed the anatomical relationship between the falx cerebri and the cingulate gyrus in 50 adults and children. Subsequently, we determined whether an arbitrary line, denoted as A (representing a 5 mm gap between the falx cerebri and corpus callosum necessary for depth electrode insertion), fell within the anterior, middle, or posterior cingulate gyrus. Results: The shape of the falx cerebri and its intersection point with the corpus callosum varied substantially across individuals, with a significant difference between children and adults (P = 0.02). The A line was located in the middle cingulate gyrus in 18 children (72%), while 3 (12%) and 4 (16%) had it located in the posterior and anterior cingulate gyrus, respectively. Among adults, 15 individuals (60%) had the A line in the middle cingulate gyrus, 10 (40%) in the posterior cingulate gyrus, and none in the anterior cingulate gyrus. Conclusion: This study demonstrates the feasibility of simultaneous sampling of both the anterior and middle cingulate gyri in adults and children. Moreover, it represents the first investigation to document the wide interindividual variability in the morphology of the falx cerebri and its association with the cingulate gyrus.

Predictors of 30-Day Mortality and Morbidity Following Craniotomy for Traumatic Brain Injury: An ACS NSQIP Database Analysis.

Traumatic brain injury (TBI) is the leading cause of death among trauma patients. Identifying preoperative factors that predict postoperative outcomes in such patients can guide surgical decision-making. The aim of this study was to develop a predictive model using preoperative variables that predicts 30-day mortality and morbidity in patients undergoing neurosurgery following TBI. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was queried between 2005 and 2017 for patients aged 18 years or older who underwent TBI-specific surgery. The primary outcome was 30-day mortality, and the secondary outcome was a composite morbidity score. Significant variables on univariate analysis with Chi-squared test were used to compute multivariable logistic regression models for both outcomes, and Hosmer-Lemeshow test was used. A total of 1634 patients met the inclusion criteria. Most patients were elderly aged >60 years (74.48%), male (63.59%), of White race (73.62%), and non-Hispanic ethnicity (82.44%). The overall 30-day mortality rate was 20.3%. Using multivariate logistic regression, 11 preoperative variables were significantly associated with 30-day mortality, including (aOR, 95% CI) age 70-79 years (3.38, 2.03-5.62) and age >80 years (7.70, 4.74-12.51), ventilator dependency (6.04, 4.21-8.67), receiving dialysis (4.97, 2.43-10.18), disseminated cancer (4.42, 1.50-13.0), and coma >24 hours (3.30, 1.40-7.80), among others. Similarly, 12 preoperative variables were found to be significantly associated with 30-day morbidity, including acute renal failure (7.10, 1.91-26.32), return to OR (3.82, 2.77-5.27), sepsis (3.27, 1.11-9.66), prior operation within 30 days (2.55, 1.06-4.95), and insulin-dependent diabetes (1.60, 1.06-2.40), among others. After constructing receiver operating characteristic curve, the model for mortality had an area under the curve (AUC) of 0.843, whereas composite morbidity had an AUC of 0.716. This model can aid in clinical decision-making for triaging patients based on prognosis in cases of mass casualty events.

Primary alveolar rhabdomyosarcoma of the brain: a case report.

BACKGROUND: Primary brain rhabdomyosarcoma is a rare primary brain malignancy with few case reports. The vast majority of cases of primary brain rhabdomyosarcoma occur in pediatric patients, and immunohistochemistry can distinguish it from embryonal subtypes; however, few cases of primary brain rhabdomyosarcoma in adults have been reported in the literature. CASE PRESENTATION: We report the case of a 26-year-old White male patient who was found to have primary brain alveolar rhabdomyosarcoma after developing headaches for several months. A brain MRI revealed a mixed cystic and solid tumor along the vermis of the cerebellum. The patient underwent a gross total surgical resection, which confirmed the diagnosis of alveolar rhabdomyosarcoma. Further staging workup for another primary focus or disseminated disease yielded negative results, confirming the diagnosis of primary alveolar rhabdomyosarcoma of the brain. CONCLUSION: The standard of care for managing this rare type of brain tumor involves surgery with adjuvant chemoradiotherapy. Further studies should be conducted for a better diagnostic and therapeutic understanding.

Association of Prostate-Specific Antigen With Age, Digital Rectal Examination, and Lower Urinary Tract Symptoms in the Lebanese Population: A Cross-Sectional Study.

BACKGROUND: Prostate cancer (PCa) is a leading cause of mortality in men worldwide. Prostate-specific antigen (PSA) testing is a standard method for PCa detection, yet its association with age, digital rectal examination (DRE) results, and lower urinary tract symptoms (LUTS) remains understudied, particularly in the Lebanese population. OBJECTIVE: This study aimed to investigate the association of PSA levels with age, DRE results, and LUTS severity among Lebanese men. METHODS: A total of 725 men aged 55-70 years were recruited from a men's health campaign at Saint George Hospital University Medical Center in Lebanon. PSA levels, DRE results, and International Prostate Symptom Score (IPSS) were assessed. Statistical analysis included Kruskal-Wallis tests and Spearman's rho correlation coefficient. RESULTS: Participants exhibited a significant correlation between age and PSA levels (r = 0.138, p < 0.01). PSA levels varied significantly across age groups (p = 0.029), with higher mean PSA levels observed in older age groups. IPSS status correlated positively with PSA levels (r = 0.23, p < 0.001), indicating higher PSA levels associated with increased LUTS severity. Abnormal DRE findings were significantly associated with elevated PSA levels (p < 0.00), suggesting their potential as an indicator of prostate abnormalities. CONCLUSION: This study highlights the importance of age-specific reference ranges for PSA levels in the Lebanese population. Elevated PSA levels were associated with older age, increased LUTS severity, and abnormal DRE findings. These findings highlight the significance of integrating PSA testing with clinical assessments for PCa detection and risk stratification in Lebanon.

Astasia-abasia and psychogenic tremor post-temporal lobectomy.

Temporal lobectomy can be complicated by somatoform disorders, psychiatric illnesses and non-epileptic psychogenic seizures. We report a woman who developed astasia-abasia and psychogenic tremor following temporal lobectomy for refractory epilepsy. To our knowledge, this type of conversion reaction following temporal lobectomy has not been previously reported.

A rare case of metastatic colon cancer to the pineal region: A case report.

Background: Colorectal cancer is the third most common cancer and the third most leading cause of death in the United States with brain being a rare site for metastasis and the pineal region being a rarer site to manifest. Case Description: We present a rare case of a 72-year-old male patient with pineal region tumor and obstructive hydrocephalus for which an endoscopic third ventriculostomy was done with biopsy of the tumor showing primary colorectal origin in a patient known to be previously healthy. Conclusion: Intracranial metastasis to the pineal region is considered rare especially in cases without widely spread systematic cancer or without presence of other metastatic lesions in the brain. The case we presented suggests that we should consider pineal region metastasis as part of our differential whenever we encounter patients with an isolated pineal lesion. Endoscopic third ventriculostomy can be a better treatment option to treat obstructive hydrocephalus caused by the lesion potentially avoiding peritoneal dissemination.

Antenatally diagnosed intraspinal-posterior mediastinal neurenteric cyst - what is the optimal management?

Neurenteric cyst is a rare congenital anomaly that belongs to the spinal dysraphism spectrum. It is classically a disease of late childhood, with some rare reports of intrauterine and adult presentation. The increase in incidental antenatal diagnosis raises new management questions. We present a case of an asymptomatic combined intraspinal-posterior mediastinal neurenteric cyst. The cyst was diagnosed on antenatal ultrasound and was initially treated with image-guided aspiration in early infancy. However, the cyst recurred and the patient developed recurrent episodes of bacterial meningitis. Two-stage surgical resection was performed, although the infection prohibited complete excision. We caution against image guided aspiration of neurenteric cysts, and suggest a management algorithm based on the available literature.

Neurosurgical Experience of Beirut Blast in the Era of Coronavirus Disease 2019 (COVID-19) from a Tertiary Referral Center.

BACKGROUND: In this paper, we shed the light on Beirut's blast that took place in the coronavirus disease 2019 (COVID-19) era. An explosion that ripped the heart of Beirut, it produced a destructive shock wave that left thousands of casualties and people homeless. This explosion, which had a mushroom-like cloud appearance similar to that of Hiroshima and Nagasaki, was described as the third-biggest explosion in human history. It was a blast that not only destroyed lives but also fell as a heavy burden on the shoulders of a country that was suffering from unprecedented economic crisis on top of the COVID-19 pandemic. Facing all this, health care providers were the first line of defense in what looked like an impossible mission. OBJECTIVE: We seek to share with the medical community our experience and the challenges we faced, as a neurosurgery team, during this event, particularly that we were short of basic medical equipment as well as intensive care unit beds since we were in the middle of an economic crisis and the peak of the COVID-19 pandemic. This prohibited us from delivering proper care, whether in the triage of patients or in the operating room, as well as postoperative care. Now, 1 year after this sad event, we revisit the whole situation and examine all the pitfalls that could have been avoided. Thus, we discuss the importance of initiating a disaster response, in particular the neurosurgical emergency response, to be better prepared to face future potential events. CONCLUSIONS: The rate-limiting step in such disasters is definitely a well-prepared trained team with a prompt and fast response. And, since time is brain, then what saves the brain is proper timing.

Salvage therapy for vagal nerve stimulator infection; Literature review and report of a delayed recurrence.

BACKGROUND: Vagal Nerve Stimulation (VNS) is one of the most common neuro-modulation based approaches for the treatment of medically intractable epilepsy. Despite advances in technology and surgical techniques, hardware infection remains a recognized and feared complication in VNS placement. Management of such infections is scarce in the literature with the majority of data available in case reports. It ranges from immediate removal of the VNS device to conservative treatment with antibiotics in an attempt to salvage the device, particularly in patients who demonstrated significant improvement in seizure frequency and quality of life. METHODS: We performed a review of the literature in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify reported cases of salvaged VNS infection. A literature search for relevant English articles was conducted using Medline. References of relevant articles were also reviewed. Articles that comprised an attempt to salvage an infected VNS were included. RESULTS: We obtained 12 articles describing an attempt to salvage an infected VNS. Out of a total of 62 reported VNS infections and 43 salvage attempts using a variety of antibiotic-based approaches, 17 cases were successfully salvaged and 26 cases failed the salvage attempt and had to be explanted eventually. Moreover, we report a case of an 18-year-old male with Lennox-Gastaut syndrome who presented21 days after VNS placement with a MRSA deep tissue infection. An attempt was made to treat the infection with long-term culture-based intravenous antibiotics, but it recurred three years later with neck wound dehiscence and positive wound culture for the same organism, and ex-plantation was thus performed. CONCLUSION: The management of VNS infections remains a dilemma for neurosurgeons. Although the idea of salvaging an infected VNS seems appealing, hardware removal seems to be inevitable despite adequate antibiotic treatment.

Surgical techniques in the management of supratentorial pediatric brain tumors: 10 years' experience at a tertiary care center in the Middle East.

BACKGROUND: The goal of this retrospective study is to present the first epidemiological data on pediatric supratentorial central nervous system (CNS) tumors in Lebanon and to review the various surgical management strategies used. METHODS: We conducted a retrospective case series of all pediatric patients who presented with a supratentorial CNS tumor and underwent surgery at our institution between 2006 and 2016. We collected and analyzed demographic characteristics, tumor location, clinical manifestations, histopathology, and surgical management strategies and outcome, and discussed them after dividing the tumors as per location and in view of published literature. RESULTS: Ninety-nine children were studied with a male-to-female ratio of 2.3:1 and a mean age of 8.5 years. The most common location was convexity (44%) and included low-grade and high-grade glial tumors, along with other miscellaneous lesions. The next location was sellar/diencephalic (34%), including craniopharyngiomas, hypothalamic/optic pathway/thalamic gliomas, hamartomas, and pituitary/Rathke's cyst, where there was notable use of endoscopic techniques (21%). Tumors in the pineal region (13%) were tectal gliomas, germ cell tumors, and pineoblastomas and were mostly treated endoscopically. The last group was lateral intraventricular tumors (8%) and was mostly choroid plexus lesions and ependymomas. Overall, the surgical objective was achieved in 95% with mild/moderate complications in 17%. CONCLUSION: A variety of pathologies may affect the pediatric population in the supratentorial region. Different surgical strategies, including microsurgical and endoscopic techniques, may be employed to remove, debulk, or biopsy these tumors depending on their location, suspected diagnosis, prognosis, and the need for treatment of possible associated hydrocephalus.

Evaluation of intractable epilepsy. Invasive monitoring.

Accurate localization of the epileptogenic zone is the fundamental key factor for successful epilepsy surgery. Despite the progress achieved in the field of neuroimaging, invasive intracranial recording is still the gold standard that helps recognize the patient population who may profit from surgery. Meticulous implantation of intracranial electrodes and judicious interpretation of their data is a definite need in a successful epilepsy program. Few centers in the Arab world are in that domain. Moreover, the society itself is not well informed to appreciate the potentials of surgical treatment of seizure disorders. In this review article, we will go over various types of intracranial recordings, discussing their indications, and the last updates for each. Some of the cases carried out at the American University of Beirut Medical Center, Beirut, Lebanon will be illustrated as examples of our current practice. Then, the future of epilepsy monitoring will be highlighted in brief.

Pediatric posterior fossa tumors outcomes: Experience in a tertiary care center in the Middle East.

BACKGROUND: Among all childhood cancers, brain tumors are second only to leukemia in incidence and are the most common solid pediatric tumors. More than 60 % of pediatric brain tumors are infra-tentorial. The first-line treatment for most infra-tentorial tumors in pediatric patients is surgical resection, with the goal of gross-total resection, relief of symptoms and hydrocephalus, and increased survival. The proximity to the fourth ventricle, and therefore, the cerebrospinal fluid (CSF) pathways, predisposes children with posterior fossa tumors to the development of obstructive hydrocephalus and multiple other co-morbidities pre and post-surgery. OBJECTIVES: This study aims to present our series of pediatric posterior fossa tumor surgeries in the Neurosurgical Department at the American University of Beirut Medical Center(AUBMC) and perform internal quality control for our single-institution consecutive series as one of the largest referral and tertiary care centers in the region. The second purpose of this retrospective study is to weigh the risks of surgery against the presumed advantages and to have specific knowledge about the complication rates, especially those related to the CSF pathway, comparing our results to those in the literature. METHODS: All pediatric patients (< 18 years of age), referred to our center from different regions in the middle east, and surgically treated for a posterior fossa tumor from June 2006 to June 2018 at the American University of Beirut Medical Center were included. A thorough review of all medical charts was performed to validate all the database records. RESULTS: The patient sample consisted of 64 patients having a mean age of 6.19 ±â€¯4.42 years and 59.37 % of whom were males. The most common tumor pathology was pilocytic astrocytoma (40.62 %) followed by medulloblastoma (35.93 %) and ependymoma. The most common type of tumor that was seen in patients that developed mutism postoperatively (n = 6, 9.37 %) was medulloblastoma (n = 4, 66.66 %). In this patient sample, 12.28 % (n = 7) of the patients developed hydrocephalus postoperatively.Midline tumors were more associated with the development of mutism(OR = 4.632, p = 0.306) and hydrocephalus (OR = 5.056, p = 0.135) postoperatively, albeit not statistically significantly.The presence of a preoperative shunt was shown to be protective against the development of CSF leak (OR = 0.636, p = 0.767), as none of the patients that came in with CSF diversion developed a CSF leak after their surgery. CONCLUSION: This study from a single center experience accompanied by a thorough literature review sheds light on the complications frequently encountered after posterior fossa tumor surgery in children. These included transient cerebellar mutism, CSF leak, and hydrocephalus as seen in some of our patients. Our findings highlight the need for prospective studies with well-defined protocols directed at assessing novel ways and approaches to minimize the risk of these complications.

Demographics and outcomes of meningioma patients treated at a tertiary care center in the Middle East.

OBJECTIVE: Meningioma is the most common intracranial primary brain tumor. Risk factors such as age and exposure to radiation as well as prognostic factors such as grade, location, and extent of surgical resection have been reported in the literature worldwide; however, to our knowledge, data from the Middle East is still warranted. In this study, we aim to identify the characteristics, risk factors and outcomes of meningioma patients treated at a multidisciplinary regional referral center in the Middle East. PATIENTS AND METHODS: This is a retrospective chart review with a prospective follow up of outcomes. It included patients diagnosed with meningioma between January 2005 and December 2015 at the American University of Beirut Medical Center. Patient's demographics, risk factors and outcomes were first retrospectively collected. Then, we conducted phone calls to all included alive patients to update their disease status and outcomes. RESULTS: One-hundred and ninety-five patients were included. 69 % had grade I tumors and around 31 % with grades II and III meningiomas. The means of the overall survival and progression free survival (PFS) were 198 and 126 months, respectively. The residence area (city vs. countryside), occupation, alcohol use, oral contraceptive use, family history of meningioma, previous head trauma, radiation exposure for head/brain imaging, cell phone use, and finally, the tumor Ki-67 protein level did not correlate with the survival outcomes. The meningioma grade and extent of resection were significant predictors of the PFS on the univariate analysis, whereas, in the multivariate analysis only previous radiotherapy was significant in prolonging PFS. CONCLUSION: In our study cohort, that included around 30 % grades II and III tumors, previous radiotherapy use was the only significant prognostic factor for longer PFS in patients diagnosed with meningioma. Future prospective studies should be conducted to evaluate genetic and molecular factors that could possibly be linked to meningioma grade and prognosis in our population of Middle Eastern patients.

Correlation of genetic alterations by whole-exome sequencing with clinical outcomes of glioblastoma patients from the Lebanese population.

INTRODUCTION: Glioblastoma (GBM) is an aggressive brain tumor associated with high degree of resistance to treatment. Given its heterogeneity, it is important to understand the molecular landscape of this tumor for the development of more effective therapies. Because of the different genetic profiles of patients with GBM, we sought to identify genetic variants in Lebanese patients with GBM (LEB-GBM) and compare our findings to those in the Cancer Genome Atlas (TCGA). METHODS: We performed whole exome sequencing (WES) to identify somatic variants in a cohort of 60 patient-derived GBM samples. We focused our analysis on 50 commonly mutated GBM candidate genes and compared mutation signatures between our population and publicly available GBM data from TCGA. We also cross-tabulated biological covariates to assess for associations with overall survival, time to recurrence and follow-up duration. RESULTS: We included 60 patient-derived GBM samples from 37 males and 23 females, with age ranging from 3 to 80 years (mean and median age at diagnosis were 51 and 56, respectively). Recurrent tumor formation was present in 94.8% of patients (n = 55/58). After filtering, we identified 360 somatic variants from 60 GBM patient samples. After filtering, we identified 360 somatic variants from 60 GBM patient samples. Most frequently mutated genes in our samples included ATRX, PCDHX11, PTEN, TP53, NF1, EGFR, PIK3CA, and SCN9A. Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). Mutations in NLRP5 were associated with decreased overall survival among the Lebanese GBM cohort (p = 0.002). EGFR and NF1 mutations were associated with the frontal lobe and temporal lobe in our LEB-GBM cohort, respectively. CONCLUSIONS: Our WES analysis confirmed the similarity in mutation signature of the LEB-GBM population with TCGA cohorts. It showed that 1 out of the 50 commonly GBM candidate gene mutations is associated with decreased overall survival among the Lebanese cohort. This study also highlights the need for studies with larger sample sizes to inform clinicians for better prognostication and management of Lebanese patients with GBM.

A child with refractory complex partial seizures, right temporal ganglioglioma, contralateral continuous electrical status epilepticus, and a secondary Landau-Kleffner autistic syndrome.

A 7-year-old, right-handed girl started to have seizures at age 1 year 4 months. She developed normally until age 4 when she had worsening of seizures with auditory verbal agnosia, complete aphasia, and a behavioral disorder fulfilling the diagnostic criteria of autism. Medical therapy failed. MRI revealed a right temporal tumor. Video/EEG monitoring at age 7 showed contralateral electrical status epilepticus in wakefulness and sleep and ipsilateral onset of seizures. Resection (ganglioglioma with excessive inflammation) resulted in seizure freedom and marked reduction of the autistic features. This case is unique for being, to our knowledge, (1) the first in which a lesion located in the right, rather than left, temporal lobe resulted in secondary falsely localizing left temporal lobe electrical status epilepticus with a clinical picture of Landau-Kleffner syndrome and autism, and (2) the fourth reported patient with lesional Landau-Kleffner syndrome to respond to resective surgery.

Quality of life after vagal nerve stimulator insertion.

AIM: Assess quality-of-life after vagal nerve stimulation and determine patient characteristics associated with improvement in quality-of-life. METHODS: Sixteen patients (11 children, 5 adults) who had vagal nerve stimulation at our center were studied. Quality-of-life was assessed pre- and post-vagal nerve stimulation using the Quality-of-Life in Childhood Epilepsy questionnaire for children and the Epilepsy Surgery Inventory-55 for adults. RESULTS: Sixteen patients who did not qualify for resective surgery were included; seven (43.75%) were males and 9 (56.25%) were females. Mean age at onset of seizures was 3.96 +/- 4.00 years and at surgery was 15.78 +/- 10.78. Follow-up time was 1.26 +/- 0.92 years. Fourteen patients (87.5%) were mentally retarded. Ten (62.5%) had cryptogenic etiology and 6 patients (37.5%) symptomatic etiology. Fifty percent had localization-related epilepsy. Six of 7 patients with generalized cryptogenic etiology (85.71%) had Lennox-Gastaut syndrome. Seizures dropped from 122.31 +/- 159.49 to 67.84 +/- 88.22 seizures/month. Seizure reduction (> 50%) correlated with improvement in total quality-of-life (p = 0.034). Post-vagal nerve stimulation, the total group scored significantly higher in the social domain (p = 0.039). In patients with localization-related epilepsy, significant improvements were detected in the social domain (p = 0.049) and in total quality-of-life (p = 0.042). CONCLUSION: Despite a diverse and small population size, we observed significant improvements in the social domain 1.26 years post-vagal nerve stimulation. In addition, there was an improvement in total quality-of-life amongst patients with partial seizures. Finally, seizure reduction was associated with quality-of-life improvement. Our results support previous studies from the West reporting improvement in quality-of-life following vagal nerve stimulation, contradict those studies that did not show such differences, and are the first coming from a developing country.