Mieke Maris

Immunohistochemical characterisation of dendritic cells in human atherosclerotic lesions: possible pitfalls

Background: Previously we demonstrated decreased blood myeloid (m) and plasmacytoid (p) dendritic cell (DC) counts in atherosclerotic patients. Therefore, we examined whether DCs, in particular DC precursors, accumulate in human plaques. Methods: Blood DC antigen (BDCA)-1, CD11c (mDCs), BDCA-2, CD123 (pDCs), langerin, fascin, S-100 (immature/mature DCs), and CD1a and CD83 (mature DCs) were investigated by immunohistochemistry of carotid arteries obtained by endarterectomy (EAS, frozen n = 11, fixed n = 11) or autopsy (fixed, n = 87). Results: Fascin and S-100 required formaldehyde fixation, other markers needed cryo-preservation. BDCA-1, BDCA-2, langerin, and S-100 appeared specific for intimal DCs, unlike CD123 and fascin (staining endothelial cells), CD11c and CD1a (staining monocytes, foam cells) or CD83 (staining lymphocytes). BDCA-1+ and BDCA-2+ cells were detected in EAS, preferentially near microvessels. S-100+ cells increased successively from intimal thickening, via pathological intimal thickening, fibrous cap atheroma and finally complicated plaques. Fascin+ cells followed the same pattern, but were more abundant. However, in lesions containing microvessels (complicated plaques, plaque shoulders and most EAS) this was partly explained by fascin positive endothelial cells. Even complicated plaques contained relatively few mature CD83+ DCs. Conclusions: Accumulation of BDCA-1 and BDCA-2 around neovessels showed that mDCs and pDCs are recruited to advanced plaques, which is in line with the previously described decline of circulating blood DCs in patients with coronary artery disease. Unexpectedly, several DC markers yielded false positive signals. Hence, some accounts on numbers, trafficking and activation of DCs in atherosclerotic plaques may require re-evaluation.

Auditory neuropathy/dyssynchrony as a cause of failed neonatal hearing screening.

The prevalence of auditory neuropathy/dyssynchrony (AN/AD) is not exactly known. We retrospectively analysed the prevalence of this condition among 135 infants who failed a neonatal screening. Hearing screening was performed by automated auditory brainstem responses (AABR). Unilateral presence of click-evoked oto-acoustic emissions with absent auditory brainstem responses was found in 4 infants. Magnetic resonance imaging of the posterior fossa showed an aplasia/hypoplasia of the ipsilateral cochlear nerve in these 4 cases. The prevalence of AN/AD was 19% in infants with confirmed hearing loss. Our findings underscore the role of AABR in neonatal hearing screening.

Prevalence of Obstructive Sleep Apnea in Children with Down Syndrome.

STUDY OBJECTIVES To evaluate the prevalence of obstructive sleep apnea (OSA) in a large cohort of children with Down syndrome (DS), and to investigate which patient- related factors correlate with disease severity. METHODS We performed a retrospective, cross-sectional study in children with DS referred for full overnight polysomnography in a tertiary care center. RESULTS Polysomnographic data are available for 122 children (70 boys), age 5.0 y (2.8-10.5), and body mass index (BMI) z-score 0.7 (-0.3 to 1.7). The overall prevalence of OSA was 66.4%. In almost half of these children severe OSA was diagnosed (obstructive AHI [oAHI] ≥ 10/h). In children with parental reports of snoring or witnessed apneas (group A), OSA was significantly more common (75.7%) than in those without these symptoms (group B) 53.8% (P = 0.019). Children in group A had more severe OSA, oAHI 5.7/h (1.7-13.8) compared to those in group B 2.2/h (0.8-8.0) (P = 0.018). A significant inverse correlation between age and oAHI (P = 0.028) was found. Sex and BMI z-score were not significantly correlated to oAHI. CONCLUSIONS Based upon full night polysomnography, an overall 66.4% prevalence of OSA was found in children with Down syndrome. Even in those with a negative history for OSA, the prevalence was 53.8%. Younger age was associated with more severe disease.

Drug-induced sedation endoscopy in pediatric obstructive sleep apnea syndrome

AIM To describe the pattern of upper airway (UA) obstruction during drug-induced sedation endoscopy (DISE) and to evaluate the outcome of DISE-directed treatment. METHODS Prospective study of DISE in surgically naive obstructive sleep apnea syndrome (OSAS) children without syndromic comorbidity or craniofacial abnormalities. Treatment was individually tailored according to UA findings during DISE and polysomnographic data. Reported values are median (lower-upper quartile). RESULTS Thirty-seven children aged 4.1 years (2.1-6.0), with body mass index z-score 0.3 (-0.9 to 0.9), and obstructive apnea-hypopnea index (oAHI) 9.0/h (6.1-19.3) were included. Adenotonsillar obstruction was found in 33 cases (89%) as an isolated entity or as part of a multi-level obstruction. These children were treated with adenotonsillectomy (n = 28), adenoidectomy (n = 3), or tonsillectomy (n = 2). The remaining four patients received non-surgical treatment. Pre-postoperative polysomnographic data in 22 patients showed a significant improvement in oAHI from 8.6/h (6.7-20.7) to 1.0/h (0.6-2.0) (P = 0.001). Only two of these 22 children had residual OSAS (oAHI ≥ 5/h), indicating a success rate of 91%. CONCLUSIONS Based on UA findings during DISE, a non-surgical treatment was proposed for 11% of children. A 91% success rate was obtained in those treated with (adeno)tonsillectomy. These data suggest that DISE may be helpful to identify patients most likely to benefit from UA surgery.

Outcome of adenotonsillectomy in children with Down syndrome and obstructive sleep apnoea

Objective To evaluate the outcome of adenotonsillectomy (AT) in a cohort of children with Down syndrome (DS) and obstructive sleep apnoea (OSA). Design Retrospective, cross-sectional study. Setting Tertiary care centre. Patients Children with DS and OSA, without previous upper airway (UA) surgery. Interventions AT and full overnight polysomnography. Main outcome results A significant improvement of the obstructive apnoea-hypopnoea index (oAHI) after AT was obtained. No differences in sleep efficiency or sleep fragmentation were found postoperatively. Almost half of the children had persistent OSA (oAHI ≥5/hour). Results Data are presented as median (lower–upper quartile). Thirty-four children were included, median age 4.0 years (2.7–5.8), body mass index (BMI) z-score 0.81 (−0.46–1.76), and oAHI 11.4/hour (6.5–22.7). The majority presented with severe OSA (58.9%). AT was performed in 22 children, tonsillectomy in 10 and adenoidectomy in two. Postoperatively, a significant improvement of the oAHI was measured from 11.4/hour (6.5–22.7) to 3.6/hour (2.1–9.5) (p=0.001), with a parallel increase of the minimum oxygen saturation (p=0.008). Children with initially more severe OSA had significantly more improvement after UA surgery (p=0.001). Persistent OSA was found in 47.1% of the children. Conclusions AT results in a significant improvement of OSA in children with DS without a change in sleep efficiency or sleep stage distribution. Severe OSA was associated with a larger reduction of OSA severity. Almost half of the children had persistent OSA, which was not correlated to age, gender or BMI z-score.

Drug-induced sedation endoscopy in surgically naive children with Down syndrome and obstructive sleep apnea

OBJECTIVE To describe the pattern of upper airway (UA) obstruction in surgically naive children with Down syndrome and obstructive sleep apnea (OSA), and to evaluate the outcome of drug-induced sedation endoscopy (DISE)-directed treatment. METHODS A prospective study of DISE in surgically naive children with Down syndrome and OSA was performed. Treatment was individually tailored based on the DISE findings and was evaluated by control polysomnography (PGS). Results are presented as median (lower-upper quartile) unless otherwise stated. RESULTS In 41 children, aged 4.2 years (range, 2.8-6.0) with a body mass z score of 1.04 (-0.55 to 1.82) and obstructive apnea-hypopnea index (oAHI) of 10.1/h (range, 6.3-23.0), DISE was performed. Adeno-/tonsillar obstruction was found in 75.6% of the patients, and these patients subsequently underwent UA surgery. Seven patients were non-surgically treated, and three received a combined treatment. A multilevel collapse was present in 85.4%. Tongue base obstruction was present in ten patients (24.4%) and epiglottic collapse in 48.8%. Pre- and postoperative PSG data were available for 25 children (adenotonsillectomy, n = 16; tonsillectomy, n = 7; adenoidectomy, n = 2). A significant improvement in oAHI from 11.4/h (range, 7.7-27.0) to 5.5/h (range, 2.1-7.6) was found. Persistent OSA was present in 52% of the children. No significant association between different DISE findings and persistent OSA could be found. CONCLUSION Most patients with Down syndrome and OSA present with multilevel collapse on DISE. Adenotonsillectomy results in a significant improvement of the oAHI; however more than half of the patients had persistent OSA, probably due to multilevel collapse. Upper airway evaluation may provide more insights into the pattern of UA obstruction in patients with persistent OSA.