Value of vessel wall magnetic resonance imaging in the diagnosis and management of cerebrovascular diseases

Background Intracranial atherosclerosis, one of the leading causes of ischemic stroke, is associated with an increased risk for recurrent stroke and dementia. Objective This work was carried out to assess suspicious lesions detected by Magnetic Resonance Angiography (MRA) and Computed Tomgraphy Angiography (CTA) for further evaluation by vessel wall MRI . Patients and methods This study was conducted on 16 patients who were admitted to Ain Shams University Specialized Hospital with establilished diagnosis of stroke (11 patients with intracranial atherosclerosis, 3 patients with CNS vasculitis and 2 patients with Moya-moya disease ) performing MRI brain including magnetic resonance angiography (MRA) that showed intracranial stenosis, who then referred to Misr Radiology Center for the evaluation of intracranial vasculopathies by vessel wall MR Imaging using 3.0-tesla (T) field strengths. Results The results showed statistically significant difference between groups as regard to significant intracranial stenosis (>50%). It was prominent among moya moya disease group (100.0%) followed by intracranial atherosclerotic groups (81.8%), whereas CNS vasculitis group shows mild intracranial stenosis (0.0%). Conclusion Intracranial vessel wall MR imaging is an adjunct to conventional angiographic imaging

Anatomy of the Middle Meningeal Artery

Introduction The middle meningeal artery (MMA) is an important artery in neurosurgery. As the largest branch of the maxillary artery, it provides nutrition to the meninges and to the frontal and parietal regions. Diseases, including dural arteriovenous fistula (DAVF), pseudoaneurysm, true aneurysm, traumatic arteriovenous fistula (TAVF), Moya-Moya disease (MMD), recurrent chronic subdural hematoma (CSDH), migraine, and meningioma, may be related to the MMA. The aim of the present study is to describe the anatomy of the MMA and to correlate it with brain diseases. Methods A literature review was performed using the PubMed, Scielo, Scientific Direct, Ebsco, LILACS, TripDataBase and Cochrane databases, with the following descriptors: neurosurgery, neuroanatomy, meninges and blood supply. Discussion The MMA is embedded in a cranial groove, and traumatic or iatrogenic factors can result in MMA-associated pseudoaneurysms or arteriovenous fistulas (AVFs). In hemodynamic stress, true aneurysms can develop. Arteriovenous fistulas, pseudoaneurysms, and true aneurysms can be effectively treated by endovascular or surgical removal. In MMD, the MMA plays a role in the development and in the improvement of collateral circulation. Finally, in cases of CSDH, when standard surgery and drainage fail, MMA embolization can constitute a great alternative. Conclusion The MMA is a relevant structure for the understanding of neurosurgical diseases. In conclusion, every neurosurgeon must know the anatomy of the MMA sufficiently to correlate it with the diagnosed pathology, thus obtaining treatment effectiveness and preventing brain lesion.

Clinical Profile of Indian Children with Down Syndrome

This retrospective study was performed on 208 patients with Down syndrome (DS) from heterogeneous ethnic population and admitted under Genetics Metabolic Unit. The aim of the study was to look for phenotypic variability and associated complications in children and adolescents with DS. The average age of the evaluated DS patients was 34 months. Cardiac anomalies were found in 128 (62%) of the 208 cases. Among the cardiac disorders, atrial septal defects accounted for 30% of cases. Other complications observed were hypothyroidism and developmental delay in around 31% cases and neonatal cholestasis in 14% cases. Also, we report two cases with Moya-Moya disease and one case with atlanto-axial dislocation.

Optic glioma in children: Turkish experience.

e14042 Background: Optic gliomas are the most common tumors of the optic pathway, comprising about 1% of all intracranial tumours. Here we present the clinical characteristics and the outcome of patients with optic glioma at our institution. Methods: Seventy two patients diagnosed and followed up at a pediatric cancer center in Ankara, Turkey between January 1, 2008 and December 31, 2020 were included in this analysis. The clinical features and outcome of patients were recorded from patient files and hospital information system retrospectively. Results: The median age at the time of diagnosis was 3.5 years (4-157 months), the female/male ratio was 1.3. Fourteen children (19%) were asymptomatic and tumors were detected with routine surveillance, and 58 (81%) had symptoms (the most common being proptosis in 16 patients (22%)). The most common site of optic glioma was the intraorbital region (31%). Fourty patients (55%) had neurofibromatosis type 1 (NF-1). Five patients had histopathological diagnoses; 3 pilomyxoid astrocytoma, 2 pilocytic astrocytoma. Children were treated if they had tumor progression on MRI and/or worsening visual acuity. Twenty seven (38%) children were observed without any therapy, 6 patients (8%) received radiation and chemotherapy, 4 patients (5%) received radiation only, and 35 patients (49%) received chemotherapy only. Treatment regimens for the 41 children who received chemotherapy included carboplatin/etoposide (17), cisplatin/etoposide (18), carboplatin/vincristine (5), and temozolomide (1). The 5-year progression-free survival (PFS) and overall survival (OS) were 64% and 90%, respectively with a 31 month median follow-up. The 5 year PFS was significantly lower in patients with optic tract-hypothalamic-chiasmatic involvement (34%) than orbital involvement (83%) (p=0.013). Five year PFS was significantly higher in patients with NF-1 (80%) than patients without NF-1(46%) (p=0.027) and significantly lower in patients diagnosed at <3 years old (37%) (p=0.05). Five patients died of disease, and one died of infection after chemotherapy. Two patients treated with platin (1 carboplatin, 1 cisplatin) developed ototoxicity. One patient with NF-1 developed Moya-Moya disease. Two patients developed multiple pituitary hormone deficiencies and one patient developed precocious puberty during follow-up. No secondary malignancy was observed. Conclusions: The management of optic glioma remains challenging. Although the overall survival for children with this disease is excellent, progression of disease is frequent, particularly in those children without NF-1, younger children and non-orbital tumors. This study from Turkey showed comparable results with high-income countries. Further studies with longer follow-up periods are needed to find appropriate treatment strategies.

Ethnic variation and the relevance of homozygous RNF 213 p.R4810.K variant in the phenotype of Indian Moya moya disease

Background and purpose Polymorphisms in Ring Finger Protein 213 (RNF 213) gene have been detected to confer genetic susceptibility to Moya moya disease (MMD) in the East Asian population. We investigated the frequency of RNF 213 gene polymorphism and its association with MMD phenotypes in the Indian population. Materials and methods A case-control study for RNF 213 polymorphism involving 65 MMD patients, 75 parents, and 120 controls were performed. A total of 21 SNPs were screened, of which 17 SNPs were monomorphic. Allelic and genotypic frequency of all polymorphic SNPs were assessed and its association with MMD phenotypes was evaluated. Results The median age of symptom onset was 9 (range 2–17) and 37 years (range 20–58) in paediatric and adult patients respectively. A strong association was observed with RNF 213 rs112735431(p.R4810K) and MMD. Out of 65 patients with MMD, five patients carried the homozygous risk AA genotype. None of the healthy controls carried this homozygous mutation. The mutant allele was detected in MMD patients from Tamil Nadu and North eastern states of India (p = <0.0001). All the patients carrying the mutant allele had an early age of onset (p = <0.0001), higher incidence of bilateral disease (p = <0.002), positive family history (p = 0.03), higher Suzuki angiographic stage (≥3) (p<0.0006) and recurrent neurological events (ischemic strokes and TIAs) (p = <0.009). Conclusion The homozygous rs112735431(p.R4810K) variant in RNF 213 variant not only predicts the risk for MMD but can also predict the phenotypic variants.

Favourable Outcome of Non Myeloablative Allogeneic HSCT in Adult Patients with Severe Sickle Cell Disease: A Single Center Experience of 110 Patients

Background: Allogeneic HSCT for adult patients with sickle cell disease (SCD) is potentially curative but not commonly utilized therapy due to complications such as graft failure (GF) and organ toxicity. At our center, we adopted a non-myeloablative (NMA) conditioning regimen in adult patients with severe SCD. Herein, we are reporting our outcome data of up to 5-years of follow up post HSCT. Methods: Following IRB approval, adult patients that underwent HSCT from 2015 to 2020 for severe SCD with at least 6 months of follow up were included. Indications for HSCT were; presence of recurrent vaso-occlusive crisis (VOC), end organ damage, multiple joint AVN, recurrent priapism, transfusion dependency, or RBC alloimmunization. Conditioning regimen consisted of alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy TBI on day -2 or -1. Pre-transplant preparation consisted of Hydroxyurea at maximum tolerated dose for 2-3 months. Peripherally mobilized stem cells targeting 10x106/kg of CD34 cells were used. For GVHD prophylaxis sirolimus was started on day -1 and continued for one year with tapering off if lymphoid chimerism is &gt; 50%. EFS was defined as time from HSCT to graft failure or death from any cause whereas OS was defined as time from HSCT to death or last documented follow up. Results: A. Baseline Characteristics: A total of 110 patients were included with a median (range) age of 27 years (14-43), 59% of patients were male. Baseline median hemoglobin and hemoglobin S (HbS) was 95 g/L (64-121) and 74 % (17 -97), respectively. Regular hydroxyurea use was among 108 (98%) and 109 (99%) of patients required at least ≥ 1 transfusion annually. Narcotic pain killers were used regularly in 21 (19%) of patients. Median pre-HSCT ferritin was 1062 and iron chelation was used in 36 (33%). The most common indications for HSCT were (overlapping) recurrent VOC in 93%, ACS in 36%, stroke in 28% and RBC allo-immunization in 26%. Furthermore, 18 patients had 3 indications, 45 had 2 indications while the remaining 47 patients had one indication. Furthermore, 10 (9%) patients had Moya-Moya disease, 5 (5%) had sickling hepatopathy and or liver cirrhosis with total bilirubin up to 670 mmol/L and 1 (1%) patient had end stage renal disease on peritoneal-dialysis. A total of 61 (55%) donors were SC trait and underwent GCSF mobilization without major adverse events as previously reported (Damlaj et al., BMT 2018). 8 (7%) and 15 (14%) had major and minor ABO incompatibility, respectively. The remaining characteristics are found in table 1 B. Transplant Characteristics and Post HSCT Outcome: Median infused CD34x106/kg was 12.4 (6.4-24.9) and 108 (98%) patients had successful engraftment. A total of 12 patients experienced GF; 2 as primary and 10 as secondary within a median time of 129 days (40-583). Outcome post GF was as follows; recurrence of SCD in 6 (50%), aplastic bone marrow in 6 (50%) of whom 4 underwent a second allogeneic HSCT with Flu-Cy-ATG platform and all from MRD. Among second HSCT recipients, 3 are still alive and in SCD free disease status. Among patients with GF, 5 (42%) had minor ABO incompatibility while the remaining 7 (58%) were ABO matched HSCT. Mild acute skin GVHD (grade I to II) occurred in 3 cases and 4 cases developed autoimmune haemolytic anemia that resolved with steroids. Only one patient had CNS bleeding 2 years post-transplant in a background of history of stroke and Moya-Moya disease. A total of 53 (48%) patients successfully discontinued sirolimus while an additional 40 (35%) are on active taper. There were a total of 4 successful pregnancies in 3 patients; 3 pregnancies completed to term while 1 miscarried. Median follow up for the cohort is 16.8 (2-66) months. Estimated 2-year EFS and OS was 87.3% (+/- 0.036) and 97% (+/-0.017). All deaths were due to GF. There was no difference in outcome (EFS or OS) between patients receiving graft from normal vs. SC trait. Post HSCT Hb and chimerism results are shown in table 2. Conclusions: Herein, we present a large real-life experience demonstrating feasibility and favourable outcome of NMA HSCT in adult patients with severe SCD including patients with significant organ dysfunction or neurologic vasculopathy. Successful pregnancies and long-term discontinuation of immune suppression was possible. Longer follow up is warranted to ascertain stability of graft function over time. Disclosure: The authors declare they have no relevant conflicts of interest Disclosures No relevant conflicts of interest to declare.

DIFFICULTIES IN DIAGNOSING MOYA-MOYA DISEASE (CLINICAL CASE)

Moya-Moya disease is a rare progressive chronic cer-ebrovascular disease characterized by a narrowing of the lumen of the intracranial segments of the internal carotid arteries, as well as the initial segments of the anterior and middle cerebral arteries with the devel-opment of a network of small vascular anastomoses. Violations of blood supply due to occlusion lead to the development of ischemic strokes in the correspond-ing pools, and ruptures of vascular anastomoses - to the development of hemorrhagic strokes, causing a variety of neurological disorders. The article presents a clinical case of Moya-Moya disease in a 31-year-old patient. The disease was manifested by acute disorders of cerebral circulation in ischemic and hemorrhagic types. The diagnosis was made in accordance with the diagnostic criteria of the disease based on the data of endovascular cerebral angiography.