A molecular study of pediatric pilomyxoid and pilocytic astrocytomas: Genome-wide copy number screening, retrospective analysis of clinicopathological features and long-term clinical outcome.

Background: Pilocytic Astrocytoma (PA) is the most common pediatric brain tumors. PAs are slow-growing tumors with high survival rates. However, a distinct subgroup of tumors defined as pilomyxoid astrocytoma (PMA) presents unique histological characteristics and have more aggressive clinical course. The studies on genetics of PMA are scarce. Methods: In this study, we report one of the largest cohort of pediatric patients with pilomyxoid (PMA) and pilocytic astrocytomas (PA) in Saudi population providing a comprehensive clinical picture, retrospective analysis with long-term follow-up, genome-wide copy number changes, and clinical outcome of these pediatric tumors. We examined and compared genome-wide copy number aberrations (CNAs) and the clinical outcome of the patients with PA and PMA. Results: The median progression free survival for the whole cohort was 156 months and it was 111 months for the PMA, however, not statistically significantly different between the groups (log-rank test, P = 0.726). We have identified 41 CNAs (34 gains and 7 losses) in all tested patients. Our study yielded the previously reported KIAA1549-BRAF Fusion gene in over 88% of the tested patients (89% and 80% in PMA and PA, respectively). Besides the fusion gene, twelve patients had additional genomic CNAs. Furthermore, pathway and gene network analyses of genes in the fusion region revealed alterations in retinoic acid mediated apoptosis and MAPK signaling pathways and key hub genes that may potentially be involved in tumor growth and progression, including BRAF, LUC7L2, MKRN1, RICTOR, TP53, HIPK2, HNF4A, POU5F, and SOX4. Conclusion: Our study is the first report of a large cohort of patients with PMA and PA in the Saudi population that provides detailed clinical features, genomic copy number changes, and outcome of these pediatric tumors and may help better diagnosis and characterization of PMA.

Challenges in Grisel's Syndrome Management in a Two-Month-Old Infant.

Grisel's syndrome (GS) is a rare neurosurgical condition involving nontraumatic rotatory subluxation of the atlantoaxial joint. This case report presents a two-month-old infant girl, the youngest reported case of this syndrome based on our literature review to the date of this publication. The infant was initially referred to our hospital as a case of the arachnoid cyst but was subsequently neuroradiologically diagnosed with GS, which was believed to be secondary to a retropharyngeal abscess. After developing weakness and developmental delay as well as failing conservative management for two years, the infant underwent C1 laminectomy and occipitocervical sublaminar wire fusion with favorable outcomes. GS should be considered a differential even if the patient does not present with typical signs such as torticollis and neck pain. If not identified early and treated effectively, it can result in severe neurological damage. The management plan largely depends on the Fielding-Hawkins grade of subluxation and the timing of diagnosis.

Atypical Teratoid Rhabdoid Tumors (ATRT): King Faisal Specialist Hospital and Research Centre experience.

BACKGROUND: Atypical teratoid rhabdoid tumor is an uncommon aggressive central nervous system tumor. All retrospective series have shown a short mean overall survival rate. Considering the rarity of the disease, few prospective clinical trials addressed treatment recommendations for such aggressive tumors, and consequently no definitive treatment guidelines have been established. In this study, we are reviewing our experience in treating atypical teratoid rhabdoid tumor patients. METHODS: We reviewed the medical charts of 43 patients with atypical teratoid rhabdoid tumor who were treated in King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, between 1996 and 2013. We evaluated the overall survival rate and the influence of different clinical features and treatment protocols on survival. RESULTS: The median overall survival time was 16.9 months (95% Confidence Interval, 5.2-32.9 months) with an estimated 2- and 5-year overall survival of 41.9% ± 9.6 and 27.9% ± 9.2, respectively. Patients receiving trimodal treatment (surgery, chemotherapy, and radiotherapy) exhibited significantly better median overall survival time compared to their counterparts (P value < .001). CONCLUSIONS: Atypical teratoid rhabdoid tumor is rare and aggressive central nervous system tumor. Despite the limitations of the study, our results support several of clinical practice development. Utilization of postoperative radiotherapy and the adoption of trimodal therapy are associated with significant improvement of median survival. Prompt management with aggressive trimodal therapy should be the standard for future treatment protocols.

Seizure outcome in moyamoya after indirect revascularization in pediatric patients: Retrospective study and literature review.

BACKGROUND: Moyamoya disease (MMD) is a unique cerebrovascular disorder characterized by progressive stenosis of anterior cerebral circulation. Moyamoya is not an uncommon disease in Saudi Arabia. Although a less common symptom of the disease, the incidence of seizure in MMD ranges from 6 to 30%. Indirect revascularization through Encephaloduroarteriosynangiosis technique is one of the surgical treatment options for MMD. In our cohort, we aim to evaluate seizure outcome in pediatric patients with moyamoya. METHODS: Eleven patients with seizure as primary presentation for MMD over a period of 10 years were included in the study. All patients underwent EDAS surgery. All patients underwent pre- and postoperative assessment of multiple factors contributing to seizure outcome. Patients were evaluated for surgery control clinically and radiologically. RESULTS: About 73% of MMD patients with seizures improved after EDAS surgery (P < 0.0005). Six patients out of 11 became seizure free. Patients with bilateral involvement of disease undergoing bilateral surgery had better seizure control than those undergoing unilateral surgery (P < 0.07). CONCLUSION: Patients with controlled seizure before surgery are more likely to be seizure free after intervention. Seizure outcome is favorable after indirect surgical revascularization in pediatric moyamoya patients.

Infantile atypical subependymal giant cell astrocytoma.

Subependymal giant cell astrocytoma is a benign WHO grade I intraventricular tumor arise in patients with tuberous sclerosis complex. Previous reported described histopathological predictors of more aggressive forms, terms atypical SEGA in infantile age group. Other reports showed possible transformation of SEGA into glioblastoma, or misdiagnosis as glioblastoma due to the presence of atypical histopathological features. Here, we report a case of an infant who presented with right frontal extraventricular SEGA and underwent craniotomy with complete resection. Eight months later, he presented with fast recurrence in same location with midline shift and subfalcine herniation. Histopathological description showed high grade features including Ki labeling index of 60%, atypical mitotic figures, cellular plemorphism and necrosis. We also discussed the possible presence of different entity (termed atypical SEGA) which may have more aggressive clinical course, with literature review of predictors of SEGA aggressiveness and possible transformation/misdiagnosis as glioblastoma.

Angiocentric glioma of brainstem.

Angiocentric glioma is a rare brain tumor commonly found in frontal or temporal lobes. It has a benign course, and surgical resection can be curative. Brainstem location is extremely rare, with only six cases reported so far in the literature. In the present study, the seventh case of brainstem angiocentric glioma has been reported, and its course in comparison with supratentorial location and the role of molecular diagnosis has been discussed.

Tectocerebellar dysraphia with occipital encephalocele: a phenotypic variant of the TMEM231 gene mutation induced Joubert syndrome.

There are few reported cases of tectocerebellar dysraphia with occipital encephalocele (TCD-OE) in the literature. This malformation was first described by Padget and Lindburg in 1972 and consists of an occipital encephalocele, a cerebellar midline defect, inverted cerebellum, and deformity of the tectum. Occurrence is believed to be sporadic with a male predominance and a usually poor prognosis. We report a patient with brain MRI findings compatible with tectocerebellar dysraphia and occipital encephalocele. Additional features consistent with Joubert syndrome including deepened interpeduncular fossa, as well as elongated, thickened, and anteroposteriorly oriented superior cerebellar peduncles, were noted. The patient's evaluation also revealed a homozygous mutation of the TMEM231 gene, known to cause Meckel-Gruber and Joubert syndromes. Our case represents the first reported genetic confirmation that tectocerebellar dysraphia with occipital encephalocele is not a distinct nosological entity but likely a phenotypic variation of Joubert syndrome.

Epidemiology of neural tube defects in Saudi Arabia.

OBJECTIVE: To evaluate the distribution and pattern of neural tube defects in Saudi Arabia by creating a hospital based registry. METHODS: All cases registered in the King Faisal Specialist Hospital and Research Center (KFSH&RC) neural tube defect (NTD) registry since it was established in October 2000 until December 2012 were studied through active surveillance comprising a registrar who collects NTD information by reviewing the patient's medical records, and interviewing patient's families. RESULTS: The total number of patients registered from October 2000 to December 2012 was 718 patients. There were more females (417, 58%) than males (301, 42%). Of 620 mothers who underwent antenatal ultrasonography; 392 (63%) were diagnosed at birth, and 204 (33%) were diagnosed with antenatal hydrocephalus. In our registry sample, most mothers (95%) did not take folic acid 3 months prior to pregnancy, and 76% did not take folic acid during the 3 months after conception with the affected child. Only 5% received folic acid prior to conception. CONCLUSION: The KFSH&RC-NTD registry has met its objectives as a source of data that may significantly contribute to the prevention of NTDs, and improving quality of care for NTD patients through active publication of registry findings and management approaches.

Central nervous system and spinal tuberculosis in children at a tertiary care center in Saudi Arabia.

BACKGROUND AND OBJECTIVES: Tuberculosis (TB) remains a global health problem. There is limited data on pediatric central nervous system tuberculosis (CNSTB) in Saudi Arabia on diagnosis and therapy. DESIGN AND SETTING: Retrospective review of health record of pediatric patients < 14 years old who were diagnosed as having CNSTB or spinal TB and admitted to a tertiary care center. PATIENTS AND METHODS: Health records and microbiology data of pediatric patients diagnosed with CNSTB were over 20-year period were reviewed. Data on demographics, clinical presentation, surgical interventions, neuroimaging, mycobacterial cultures and susceptibility and treatment were collected. RESULTS: Thirteen children were diagnosed with CNSTB or spinal TB. Tuberculoma was the most frequent in 8 cases (62%), followed by TB of the spine in 4 cases (31%), and one case of meningitis. Six patients had a history of TB contact (46%) and 8 (62%) patients had a positive tuberculin skin test (TST). Seizure and weakness was the most frequent symptoms (38% each), while fever was less frequently encountered (23%). Tissue cultures (brain tissues/spinal tissues) showed a high yield (92%) of Mycobacterium tuberculosis with positive cultures for 11 surgical specimens out of 12 for whom cultures were done. There were no surgical complications from biopsies. All of MTB isolates were sensitive to first-line agents. CONCLUSIONS: Brain or spinal biopsy is safe and has a high culture yield for MTB so it is advisable to perform a biopsy for any child in whom CNSTB is suspected and when there is no other less risky involved site for biopsy. All MTB isolates in this series were sensitive to first-line anti-tubercular agents.