INSTABILIDADE ATLANTOAXIAL EM CRIANÇAS COM SÍNDROME DE DOWN

It is characterized by mental retardation, as well as craniofacial, upper airway, cardiovascular, and gastrointestinal anomalies. One manifestation of DS relevant to anesthesiologists is upper cervical spine instability produced by ligamentous laxity, skeletal anomalies, or both. This instability can result in neurologic impairment, including quadriplegia. However, there are no evidencebased practical guidelines to aid anesthesiologists in caring for these patients. The risk of spinal cord injury during anesthesia is unknown, as are the preoperative factors that might aid in accurately defining the risk in specific patients. Review of Normal Upper Cervical Spine Anatomy The structures relevant to this discussion include the base of the skull, the atlas (C1), and the axis (C2). The articulations between these structures are complex but are designed to facilitate maximal movement without compressing the spinal cord. The motions are flexion extension and rotation; little lateral bending occurs in this area.

To clarify etiology, clinical features, and diagnostic and treatment options of atlantoaxial dislocation (AAD) due to os odontoideum (OsO) in patients with Down's syndrome (DS). We described and analyzed three clinical cases of AAD due to OsO in DS patients and reviewed descriptions of similar cases in the scientific sources. According to literature review, more than 80% of DS patients with odontoid ossicles had atlantoaxial instability (AAI). AAI in DS patients with OsO is more often manifested in childhood and adolescence, rarely in adults when ligament relaxation is reduced. Some patients had acute clinical manifestation after a minor trauma without any precursors; in some of the cases, neurological deterioration increased during several years. We found that the earlier surgical treatment of AAD due to OsO in DS patients carries the higher recovery potential. Most patients with DS and OsO had AAI. The method of appropriate treatment in such cases is a posterior screw fixation. Preoperative halo traction and posterior fusion have proved to be a very useful tool in the treatment of AAD due to OsO in DS patients. Even if irreducibility of the AAD established preoperatively, it should not be an absolute indication for anterior decompression. In such cases, an attempt to reduce the AAD should be made under general anesthesia during posterior fixation.

Background: Os odontoideum is a congenital anomaly or a posttraumatic event of the C2 vertebra (dens), in which the odontoid process is separated from the body of the axis by a transverse gap. Trivial trauma aggravates the condition resulting in atlantoaxial dislocation (AAD) which needs stabilization. Materials and Methods: In our study, we have five patients with os odontoideum, who had developed quadriparesis after minor cervical trauma. All of them underwent C1–C2 posterior stabilization by Harms technique (C1 lateral mass screw and C2 pedicle screw with rod reconstruction), and postoperatively, all the five patients showed a significant improvement from the quadriparesis. Results: All the patients in this case series showed significant improvement in motor power following posterior C1 C2 stabilization. Conclusion: AAD following a trivial trauma in cases of os odontoideum needs to be stabilized to form solid fusion. To achieve that, the Harms technique of C1–C2 fusion is a very effective method.

Background Children with Down syndrome (DS) differ from typical children because of many genetic-related aspects that may affect outcomes after congenital heart surgery. To date, there have been no studies on outcomes after congenital heart surgery on pediatric DS patients in Indonesia.
 Objective To determine outcomes and mortality in DS patients who underwent heart surgery at Dr. Cipto Mangunkusumo Hospital, Jakarta.
 Methods A prospective and retrospective cohort study was conducted in DS patients aged <15 years who underwent heart surgery from July 2007 to April 2015. The control group were patients in the same age range without DS who underwent heart surgery for various types of heart defects.
 Results There were 57 DS and 43 non-DS patients during study period. The types of heart defects found in DS patients were atrioventricular septal defect (AVSD) and ventricular septal defect (VSD) in 18/57 (31.6%) patients each, tetralogy of Fallot (12/57; 21%), atrial septal defect (ASD) (4/57; 7%), patent ductus arteriosus (PDA) (4/57; 7%) and transposition of the great arteries with VSD (TGA-VSD) (1/57; 1.8%). DS patients showed an increased incidence of preoperative PH (63.1%) compared to non-DS patients (25.6%). Median duration of surgery was longer in DS [2.9 (range 0.5-5.8) hours] than in non-DS [2.2 (range 0.7-4.7) hours]. DS patients have a longer mean cardiopulmonary bypass duration [79.5 (SD 33.9) minutes] compared to non-DS [59.9 (SD 23.6) minutes], longer mean aortic cross-clamp duration [45.3 (SD 23.7) minutes] compared to non-DS [34.8 (SD 15.7)]. There were significant differences in the incidence of preoperative pulmonary hypertension, surgical time, duration of cardiopulmonary bypass (CPB), and length of the aortic cross-clamp in DS patients compared to non-DS (P<0.05). Median length of ICU stay was 1.9 (range 0.6 to 34) days in DS and 1 (range 0.3 to 43) day in non-DS patients (P=0.373). Median duration of mechanical ventilation [19.9 (range 3-540) vs. 8 (range 3-600) hours (P=0.308)], rate of pulmonary complications [14/57 (24.6%) vs. 6/43 (14%) patients (P=0.216)], and incidence of sepsis [16/57 (28.1%) vs. 6/43 (14%) patients (P=0.143)] were not significantly different between DS and non-DS patients. However, complete atrioventricular (AV) block only occurred in DS patients [6/57 (10.5%)]. In the DS group, 5/57 (8.8%) patients died. There was no mortality in the non-DS group.
 Conclusion Morbidity and mortality after cardiac surgery in were higher in DS than in non-DS patients. DS patients may have problems related to preoperative PH, AV block, longer surgical time, duration of CPB, and aortic cross-clamp compared to non-DS.

To the Editor: The presence of Down’s syndrome (DS) associated with moyamoya disease has been increasingly noted in the last years. Several reports suggest that the incidence of moyamoya disease is higher in children with DS than in other children. Since 1977, when this association was described for the first time, more than twenty cases have been reported.1 2 3 However, the reason of this association is unknown. Furthermore, DS is associated with autoimmune disorders.4 We describe a child with trisomy 21 affected by moyamoya and Graves’ disease, associated with anti-thyroid microsome antibodies and antiphospholipid antibodies (aPL). This patient was included in the prospective study of stroke in young adults in Cantabria, Spain.5 6 A 21-year-old man was admitted to the hospital on May 27, 1986. Thirteen days before, his mother noticed a sudden muscle weakness in his left arm; 3 days later she also noted that he had difficulty in walking because of a weakness in his left leg. The patient was the eighth pregnancy of a mother who was 39 years of age at the time of delivery. When he …

Down Syndrome (DS) Patients with Intermediate Risk (IR) Acute Lymphoblastic Leukemia (ALL): Events and Outcome on Children's Cancer Group (CCG) 1891 Study.

10510 Background: Patients with DS and B-ALL experience increased rates of relapse and toxicities. Here, we report results from 4 COG trials (2003-2018). Methods: We analyzed clinical, and outcome data for DS (n = 743) and non-DS (n = 21,703) patients age 1-30 enrolled on standard-risk (SR) trials AALL0331 and AALL0932 and high-risk (HR) trials AALL0232 and AALL1131. Initially, DS-ALL patients on AALL0232/AALL0331 experienced excess mortality, prompting enhanced supportive care and omission of induction anthracycline except for slow responders on AALL1131. Other modifications included: non-random assignment to treatment strata without investigational agents; leucovorin rescue after intrathecal methotrexate (MTX); equal maintenance length for boys and girls; every 12-week maintenance vincristine/steroid pulses; and reduced anthracycline and intravenous MTX for HR patients. Results: Across all 4 trials, DS and non-DS patients did not differ significantly in age, sex, initial WBC, or CNS status. DS-ALL patients had significantly higher end of induction (EOI) minimal residual disease (MRD) vs non-DS patients on both AALL0932 and AALL1131, but the difference persisted at end of consolidation (EOC) only on AALL1131, with fewer EOI MRD+ DS patients achieving EOC MRD < 0.01% (76.1 vs 88.0%, p = 0.001). 5-year EFS and OS were significantly poorer for DS vs non-DS across all trials (EFS 79.6+2.1% vs 86.3+0.3%, p < 0.0001; OS 86.5+1.8% vs 93.1+0.2%, p < 0.0001), as well as on each individual trial. In Cox regression analysis for all DS patients, inferior EFS was associated with several known risk factors (age > 10, EOI MRD >0.01%) but not with cytogenetics or CRLF2 status Induction death was more frequent in DS patients (3.4% vs 0.8%, p < 0.0001) as was death in remission (4.8+0.8% vs 1.8+0.1%, p < 0.0001). For death in remission, the increased frequency occurred pre-maintenance and in patients taken off protocol therapy, but not during maintenance, in contrast to prior reports. Grade >3 mucositis, infections, and hyperglycemia were significantly more frequent in DS patients on all trials. Grade >3 seizures were significantly more frequent in DS patients on HR but not SR trials (4.1% vs 1.7%. p = 0.001) and occurred in all phases pre-maintenance. Conclusions: Patients with DS and B-ALL continue to have inferior outcomes compared to non-DS, with increased relapse and toxicities. Less toxic approaches such as immunotherapies and targeted therapies hold promise to improve outcomes in both these areas.

Surgical Fixation Using Screw-Rod Construct Instrumentation for Upper Cervical Instability in Pediatric Down Syndrome Patients

Acute Lymphoblastic Leukemia in Children with Down Syndrome: A Report From the Ponte Di Legno Study Group,

Improved Outcome of Children with Down Syndrome (DS) and High Risk Acute Lymphocytic Leukemia (HR-ALL): A Report of CCG-1961.

Congenital heart defects (CHD) are found in ~50 % of Down syndrome (DS) patients. Genetic variants have been implicated, including CRELD1 mutations, but no previous study has examined the candidate genes, NKX2-5 and GATA4, in DS patients with secundum atrial defects (ASDII) and ventricular septal defects (VSD). Furthermore, CRELD1 mutations have not yet been studied in Mexican DS patients with atrioventricular septal defects (AVSD). Mexican DS patients (n = 148) with standard trisomy 21 were classified as follows: group I, normal heart; group II, VSD, ASDII, or both; and group III, AVSD. Mexican healthy controls (n = 113) were also included. Sequence analysis was performed on NKX2-5 and GATA4 in all three groups, and on CRELD1 in only group III. Statistical differences in the percentages of functional variants were analyzed by Fisher's exact test. Three non-synonymous variants in NKX2-5 were identified in the heterozygous state: a novel p.Pro5Ser was found in one DS patient without CHD; the p.Glu21Gln was found in one ASDII patient; and the p.Arg25Cys (R25C) was found in three patients (one from each DS study group). The p.Glu21Gln and R25C were also documented in 0.88 % of the controls. No significant difference was observed between the DS groups and healthy controls. Germline mutations in the NKX2-5, GATA4, and CRELD1 genes do not appear to be associated with CHD in Mexican DS patients. Our findings also support the notion that the R25C variant of NKX2-5 is a polymorphism, as it was not significantly different between our DS patients and controls.

Although 10% to 60% of patients with Down syndrome (DS) develop atlantoaxial instability (AAI), clarifying the course of asymptomatic AAI may prevent unnecessary clinical interactions and investigations. This study investigates the radiographic changes observed in asymptomatic AAI associated with DS in Japanese children as they grow from infancy to adolescence over a minimum of 10 years. A retrospective analysis of cervical radiographs acquired from asymptomatic patients with DS in both infancy and adolescence was carried out. Radiographic evaluation included measuring the atlantodental interval (ADI) and the space available for the cord (SAC). In neutral lateral cervical radiographs, AAI was defined as ADI >6mm and SAC <14mm. Two hundred thirty-nine patients were included. The mean follow-up was 12.8 years. ADI was 2.3mm at initial evaluation and 2.7mm at final evaluation ( P <0.01) in a neutral position, 3.1 and 3.3mm in flexion ( P =0.18), and 1.7 and 2.1mm in extension ( P <0.01), respectively. SAC was 15.8mm at initial evaluation and 20.9mm at final evaluation ( P <0.01) in neutral position, 15.6 and 20.7mm in flexion ( P <0.01), and 16.8 and 21.0mm in extension ( P <0.01), respectively. Forty-five patients (18.8%) showed evidence of AAI at the initial evaluation with 4 patients meeting the threshold for AAI at the final evaluation, one of which had os odontoideum. In contrast, of the 194 patients who did not have AAI at the initial evaluation, 3 (1.3%) developed AAI at the final evaluation. One of these with a normal den developed AAI at 13 years. As 1 patient with a normal dens developed AAI at 13 years, we recommend screening for AAI with X-ray in infancy and adolescence regardless of the presence or absence of an os odontoideum. Level IV.

Immunogenicity of a recombinant DNA hepatitis B vaccine in institutionalized patients with Down's syndrome

Antioxidant intervention attenuates oxidative stress in children and teenagers with Down syndrome

Dementia frequently occurs in Down syndrome (DS) patients, and early intervention is important in its management. We have previously demonstrated a positive correlation of plasma β-amyloid Aβ42 levels and negative correlations of Aβ40 and tau levels with dementia in DS. In this study, we examined more cases and constructed composite scores with both tau and amyloids to correlate with dementia in DS. Plasma Aβ42, Aβ40, and tau proteins were measured by an immunomagnetic reduction assay in DS patients. Data were randomly and repeatedly split into training and validating sets, and logistic regression was applied to calculate the area under the curve (AUC) for each biomarker. A total of 73 DS patients (among them, 23 had neurodegeneration) and 77 controls were recruited. In DS patients without dementia, plasma Aβ40 and tau levels were highly elevated, but Aβ42 levels were lower than those of the healthy controls. DS patients with dementia, compared with DS patients with no dementia, had a large decline in Aβ40 and tau but a rise in Aβ42. For biomarker scores correlating with dementia, Aβ40 revealed an AUC of 0.912; the composite score of Aβ40 × tau revealed an AUC of 0.953; and a combined composite score of 0.1 for Aβ40 × Tau +0.9 Tau × Aβ40/Aβ42 achieved the highest AUC of 0.965. Therefore, composite biomarker scores including both plasma tau and β-amyloid levels correlate with dementia in DS better than using individual biomarker scores. The pattern of tau decline and Aβ42 rise in DS patients with dementia are also different from previous findings in Alzheimer's disease.