Development of a highly sensitive and specific intact proviral DNA assay for HIV-1 subtype B and C.

INTRODUCTION: HIV reservoir quantification is essential for evaluation of HIV curative strategies and may provide valuable insights about reservoir dynamics during antiretroviral therapy. The Intact Proviral DNA Assay (IPDA) provides the unique opportunity to quantify the intact and defective reservoir. The current IPDA is optimized for HIV-1 subtype B, the dominant subtype in resource-rich settings. However, subtype C is dominant in Sub-Saharan Africa, jointly accounting for around 60% of the pandemic. We developed an assay capable of quantifying intact and defective proviral HIV-1 DNA of subtype B and C. METHODS: Primer and probe sequences were strategically positioned at conserved regions in psi and env and adapted to subtype B&C. In silico analysis of 752 subtype B and 697 subtype C near-full length genome sequences (nFGS) was performed to predict  the specificity and sensitivity. Gblocks were used to determine the limit of blank (LoB), limit of detection (LoD), and different annealing temperatures were tested to address impact of sequence variability. RESULTS: The in silico analysis showed that the HIV-1 B&C IPDA correctly identified 100% of the intact subtype B, and 86% of the subtype C sequences. In contrast, the original IPDA identified 86% and 12% of these subtype B and C sequences as intact. Furthermore, the HIV-1 B&C IPDA correctly identified hypermutated (87% and 88%) and other defective sequences (73% and 66%) for subtype B and C with comparable specificity as the original IPDA for subtype B (59% and 63%). Subtype B cis-acting sequences were more frequently identified as intact by the HIV-1 B&C IPDA compared to the original IPDA (39% and 2%). The LoB for intact proviral DNA copies was 0, and the LoD for intact proviral DNA copies was 6 (> 95% certainty) at 60 °C. Quantification of 2-6 copies can be performed with > 80% certainty. Lowering the annealing temperature to 55 °C slightly lowered the specificity but prevented exclusion of samples with single mutations in the primer/probe region. CONCLUSIONS: We developed a robust and sensitive assay for the quantification of intact and defective HIV-1 subtype B and C proviral DNA, making this a suitable tool to monitor the impact of (large-scale) curative interventions.

Altered lipid metabolism in synovial fibroblasts of individuals at risk of developing rheumatoid arthritis.

OBJECTIVE: Fibroblast-like synoviocytes (FLS) can augment the inflammatory process observed in synovium of patients with rheumatoid arthritis (RA). A recent transcriptomic study in synovial biopsies revealed changes in metabolic pathways before disease onset in absence of synovial tissue inflammation. This raises the question whether alterations in cellular metabolism in tissue resident FLS underlie disease pathogenesis. MATERIALS AND METHODS: To study this, we compared the metabolic profile of FLS isolated from synovial biopsies from individuals with arthralgia who were autoantibody positive but without any evidence of arthritis (RA-risk individuals, n = 6) with FLS from patients with RA (n = 6), osteoarthritis (OA, n = 6) and seronegative controls (n = 6). After synovial digestion, FLS were cultured in vitro and cellular metabolism was assessed using quantitative PCR, flow cytometry, XFe96 Seahorse Analyzer and tritium-labelled oleate oxidation assays. RESULTS: Real-time metabolic profiling revealed that basal (p < 0.0001) and maximum mitochondrial respiration (p = 0.0024) were significantly lower in RA FLS compared with control FLS. In all donors, basal respiration was largely dependent on fatty acid oxidation while glucose was only highly used by FLS from RA patients. Moreover, we showed that RA-risk and RA FLS are less metabolically flexible. Strikingly, mitochondrial fatty acid ß-oxidation was significantly impaired in RA-risk (p = 0.001) and RA FLS (p < 0.0001) compared with control FLS. CONCLUSION: Overall, this study showed several metabolic alterations in FLS even in absence of synovial inflammation, suggesting that these alterations already start before clinical manifestation of disease and may drive disease pathogenesis.

Flat Γ Moiré Bands in Twisted Bilayer WSe_{2}.

The recent observation of correlated phases in transition metal dichalcogenide moiré systems at integer and fractional filling promises new insight into metal-insulator transitions and the unusual states of matter that can emerge near such transitions. Here, we combine real- and momentum-space mapping techniques to study moiré superlattice effects in 57.4° twisted WSe_{2} (tWSe_{2}). Our data reveal a split-off flat band that derives from the monolayer Γ states. Using advanced data analysis, we directly quantify the moiré potential from our data. We further demonstrate that the global valence band maximum in tWSe_{2} is close in energy to this flat band but derives from the monolayer K states which show weaker superlattice effects. These results constrain theoretical models and open the perspective that Γ-valley flat bands might be involved in the correlated physics of twisted WSe_{2}.

Modelling fungal hypha tip growth via viscous sheet approximation.

In this paper we present a new model for single-celled, non-branching hypha tip growth. The growth mechanism of hypha cells consists of transport of cell wall building material to the cell wall and subsequent incorporation of this material in the wall as it arrives. To model the transport of cell wall building material to the cell wall we follow Bartnicki-Garcia and Gierz in assuming that the cell wall building material is transported in straight lines by an isotropic point source. To model the dynamics of the cell wall, including its growth by new material, we use the approach of Campàs and Mahadevan, which assumes that the cell wall is a thin viscous sheet sustained by a pressure difference. Furthermore, we include a novel equation which models the hardening of the cell wall as it ages. We validate the new model by comparing it to experimental data.

The intricate anatomy of the periodontal ligament and its development: Lessons for periodontal regeneration.

The periodontal ligament (PDL) connects the tooth root and alveolar bone. It is an aligned fibrous network that is interposed between, and anchored to, both mineralized surfaces. Periodontal disease is common and reduces the ability of the PDL to act as a shock absorber, a barrier for pathogens and a sensor of mastication. Although disease progression can be stopped, current therapies do not primarily focus on tissue regeneration. Functional regeneration of PDL may be achieved using innovative techniques, such as tissue engineering. However, the complex fibrillar architecture of the PDL, essential to withstand high forces, makes PDL tissue engineering very challenging. This challenge may be met by studying PDL anatomy and development. Understanding PDL anatomy, development and maintenance provides clues regarding the specific events that need to be mimicked for the formation of this intricate tissue. Owing to the specific composition of the PDL, which develops by self-organization, a different approach than the typical combination of biomaterials, growth factors and regenerative cells is necessary for functional PDL engineering. Most specifically, the architecture of the new PDL to be formed does not need to be dictated by textured biomaterials but can emerge from the local mechanical loading conditions. Elastic hydrogels are optimal to fill the space properly between tooth and bone, may house cells and growth factors to enhance regeneration and allow self-optimization by the alignment to local stresses. We suggest that cells and materials should be placed in a proper mechanical environment to initiate a process of self-organization resulting in a functional architecture of the PDL.

Urban-rural inequalities in suicide mortality: a comparison of urbanicity indicators.

BACKGROUND: Urban-rural disparities in suicide mortality have received considerable attention. Varying conceptualizations of urbanity may contribute to the conflicting findings. This ecological study on Germany assessed how and to what extent urban-rural suicide associations are affected by 14 different urban-rural indicators. METHODS: Indicators were based on continuous or k-means classified population data, land-use data, planning typologies, or represented population-based accessibility indicators. Agreements between indicators were tested with correlation analyses. Spatial Bayesian Poisson regressions were estimated to examine urban-rural suicide associations while adjusting for risk and protective factors. RESULTS: Urban-rural differences in suicide rates per 100,000 persons were found irrespective of the indicator. Strong and significant correlation was observed between different urban-rural indicators. Although the effect sign consistently referred to a reduced risk in urban areas, statistical significance was not universally confirmed by all regressions. Goodness-of-fit statistics suggested that the population potential score performs best, and that population density is the second best indicator of urbanicity. Numerical indicators are favored over classified ones. Regional planning typologies are not supported. CONCLUSIONS: The strength of suicide urban-rural associations varies with respect to the applied indicator of urbanicity. Future studies that put urban-rural inequalities central are recommended to apply either unclassified population potentials or population density indicators, but sensitivity analyses are advised.

[Preventive dentistry 7. Getting rid of halitosis]. / Preventieve tandheelkunde 7. Halitose de mond uit helpen.

Halitosis or bad breath is a problem that affects many people and its source is generally found in the oral cavity (intra-oral halitosis). Bacteria in the oral cavity produce volatile sulphur compounds such as hydrogen sulphide and methyl mercaptan that not only emit an unpleasant odour, but may also have toxic effects on the periodontal tissues. Good oral hygiene, a healthy periodontium and healthy teeth are the basis for the prevention of intra-oral halitosis and dentists and dental hygienists therefore play an essential role in its prevention.

Autoantibody Specificities and Type I Interferon Pathway Activation in Idiopathic Inflammatory Myopathies.

Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients.

Long-Term Patient-Reported Outcomes following Oncological Facial Reconstructive Surgery using the FACE-Q Skin Cancer Module.

Background: Long-term patient-reported outcomes (PROs) of oncological facial reconstructive surgery are unknown. Objective: The present study aimed to assess long-term PROs and to identify possible correlations between patient and treatment characteristics and long-term PROs. Methods & Materials: Between 2006 and 2011, 202 patients underwent facial reconstruction after Mohs micrographic surgery for non-melanoma skin cancer at our institution. After 10 years of follow-up, 96 out of the remaining 122 patients completed the FACE-Q Skin Cancer Module. Results: Patients who were surgically treated for squamous cell carcinoma reported poorer scores on the satisfaction with facial appearance (p=0.038), appraisal of scars (p=0.039) and appearance-related psychosocial distress scales (p=0.036) compared to patients with basal cell carcinoma and lentigo maligna. Finally, female patients reported significantly higher scores on the Cancer Worry Scale than male patients (p=0.047). Conclusion: Long-term patient satisfaction with respect to their facial appearance and scars after reconstructive surgery for skin cancer was comparable to short-term patient satisfaction, whereas Cancer Worry Scale and psychosocial distress appeared to be slightly higher. Our results can be used to better inform patients on the long-term effects of facial reconstructive surgery on patient satisfaction and quality of life, which are important to improve patient counselling, patient expectation management and shared decision-making.

Wrap plication of megaureter around normal-sized ureter for complete duplex system reimplantations.

PURPOSE: A duplex collecting system is a common congenital renal tract abnormality associated with different clinical problems. We describe our experience with ureteral reimplantations of a complete duplex collecting system where 1 megaureter needing recalibration and 1 normal-sized ureter coexisted. Recalibration of the megaureter was done by wrap plication around the normal-sized ureter. MATERIALS AND METHODS: Operative logs and case notes were reviewed of consecutive children with a complete duplex collecting system treated with wrap plication of the megaureter around the normal-sized ureter and reimplantation between 1997 and 2010. Reoperation, vesicoureteral reflux and obstruction rates were assessed. RESULTS: A total of 25 children underwent wrap plication and ureteral reimplantation. Of the cases 19 (76%) were completely successful and 6 (24%) needed reoperation. Three children (12%) had persistent high grade vesicoureteral reflux, 2 (8%) underwent endoscopic correction and 1 (4%) underwent repeat reimplantation of the duplex system. Three children (12%) had postoperative obstruction and 2 (8%) underwent endoscopic incision of the ureteral orifice. In 1 child (4%) a nonfunctioning lower moiety of the kidney developed, which was managed by heminephrectomy. CONCLUSIONS: Wrap plication of a megaureter around the normal-sized ureter before reimplantation seems to be a relatively safe method in the surgical management of children with a complete duplex collecting system of the kidney. Sufficient spatulation of the lower pole ureter seems to be crucial.

Increased sexual health after restored genital sensation in male patients with spina bifida or a spinal cord injury: the TOMAX procedure.

PURPOSE: In this study we prospectively investigated the contribution of restored penile sensation to sexual health in patients with low spinal lesions. MATERIALS AND METHODS: In 30 patients (18 with spina bifida, 12 with spinal cord injury, age range 13 to 55 years) with no penile sensation but good groin sensation the new TOMAX (TO MAX-imize sensation, sexuality and quality of life) procedure was performed. This involves microsurgical connection of the sensory ilioinguinal nerve to the dorsal nerve of the penis unilaterally. Extensive preoperative and postoperative neurological and psychological evaluations were made. RESULTS: A total of 24 patients (80%) gained unilateral glans penis sensation. This was initially felt as groin sensation but transformed into real glans sensation in 11 patients (33%). These patients had better overall sexual function (p = 0.022) and increased satisfaction (p = 0.004). Although 13 patients (43%) maintained groin sensation, their satisfaction with sexuality was only slightly less than that of those with glans sensation. Improved sensations helped them manage urinary incontinence, thereby improving personal hygiene and independence. Most patients felt more complete and less handicapped with their penis now part of their body image. They also reported having more open and meaningful sexual relationships with their partners. CONCLUSIONS: Tactile and erogenous sensitivity was restored in the glans penis in patients with a low spinal lesion. This new sensation enhanced the quality of sexual functioning and satisfaction. The TOMAX procedure should become standard treatment for such patients.

Spring-assisted posterior vault expansion in multisuture craniosynostosis.

PURPOSE: Patients with Apert and Crouzon syndromes and craniofrontonasal dysplasia need a vault expansion within the first year of life to treat or prevent the development of raised intracranial pressure. Many craniofacial units perform a conventional posterior vault expansion as initial surgery; an alternative to this technique is the spring-assisted posterior vault expansion. The purpose of this study was to demonstrate the efficacy of spring-assisted posterior vault expansion and to compare this technique with the conventional method. METHODS: A retrospective study was conducted among all consecutive patients who received a posterior vault expansion between 2006 and 2011. Patients treated with springs were compared with patients treated with the conventional technique for blood loss, duration of surgery, postoperative hospital admittance, increase in skull circumference and anterior-posterior length, and complications. RESULTS: Of the 31 included patients, 15 were treated with springs, and 16, with the conventional technique. Patients treated with springs had a significantly larger increase in skull circumference and anterior-posterior length, and not significant changes in blood loss compared with the conventional group. Complications in the conventional group were the following: minor dural tear in three patients, problematic wound healing in one patient, and insufficient expansion in one patient. Spring-related complications included skin perforation in two patients, a minor dural tear in two patients, and leakage of cerebrospinal fluid after an unnoticed dural tear during spring placement in one patient. CONCLUSION: Spring-assisted posterior vault expansion has some advantages over the conventional technique and is, therefore, the preferred technique in our center.

Endoscopic third ventriculocisternostomy in hydrocephalic children under 2 years of age: appropriate or not? A single-center retrospective cohort study.

PURPOSE: Treating hydrocephalus can be difficult in children under the age of 2 years because a high amount of uncertainty exists as to which treatment to perform. In this retrospective cohort study, we analyzed children under the age of 2 years with hydrocephalus undergoing an endoscopic third ventriculocisternostomy (ETV) with respect to ETV outcome. METHODS: In 59 consecutive patients under the age of 2 years, an ETV was performed between 1999 and 2010 at the Erasmus MC, Sophia Children's Hospital. Demographics, etiology of hydrocephalus, and radiological data were extracted retrospectively from the patients' medical records and operative reports and related to outcome. ETV Success Score (ETVSS) was used to retrospectively calculate the probability of success related to the actual outcome. RESULTS: In this series, 42.4 % of patients had a successful ETV. The only statistically significant finding concerned age. The failed ETV patients appeared to be younger (0.52 ± 0.60 vs. 0.86 ± 0.56 year, p = 0.005), and when using a cutoff age of 6 months only, five out of 32 infants had a successful ETV (p = 0.002). Of the children with an arachnoid cyst, 57.1 % were treated successfully with an ETV. Of the five patients with a high probability of ETV success, four (80 %) were indeed successfully treated with ETV (p = 0.049). CONCLUSIONS: Our data confirm the overall ineffectiveness of an ETV in children under the age of 6 months. Nevertheless, using the ETVSS is recommended to aid in the decision-making process even in patients under the age of 6 months.

Newborns with myelomeningocele: their health-related quality of life and daily functioning 10 years later.

OBJECTIVE: Ten years ago, the authors reported on the outcome of their study investigating the degree of discomfort and pain in newborns with myelomeningocele (MMC), using the parameters of unbearable and hopeless suffering. In the current study, they investigated the quality of life, daily functioning, pain and fatigue, ability to communicate, and number of surgeries in the same cohort of patients. They subdivided their study population into severe (Lorber) and less severe (non-Lorber) cases and compared these cases with a healthy population (non-MMC group) and with each other. METHODS: The parents of 22 of 28 patients gave informed consent for this study. The KIDSCREEN-27 and PEDI-CAT (Pediatric Evaluation of Disability Inventory) were used to assess quality of life and daily functioning. Pain and fatigue were self-reported on a 10-point numeric rating scale. Communication and ambulation levels were determined using the Communication Function Classification System (CFCS) and the Hoffer ambulation scale. Using reference data from the KIDSCREEN-27 and PEDI-CAT, the authors created a healthy population comparison group. RESULTS: There was no significant difference in health-related quality-of-life (HRQOL) scores between Lorber and non-Lorber patients, except that school environment domain scores were lower in the Lorber group. When comparing the HRQOL of MMC patients with that of the non-MMC group, the physical well-being and parent relations and autonomy domains scored significantly lower. The daily functioning of MMC patients was lower on all domains of the PEDI-CAT compared with the non-MMC group. Lorber MMC patients scored lower on all domains of the PEDI-CAT when compared with non-Lorber patients. All patients were capable of communicating effectively; most patients (n = 18) were considered CFCS level I, and 4 patients were considered CFCS level II. CONCLUSIONS: This study shows that MMC is a severe, lifelong condition that affects patients' lives in many domains. All the patients in this study are capable of effective communication, irrespective of severity of MMC. Overall, the data show that in newborn MMC patients, future unbearable suffering with respect to pain, mobility, cognition, and communication is hard to predict and may not always occur.

International Children's Continence Society's recommendations for therapeutic intervention in congenital neuropathic bladder and bowel dysfunction in children.

PURPOSE: We present a consensus view of members of the International Children's Continence Society on the therapeutic intervention in congenital neuropatic bladder and bowel dysfunction in children. MATERIAL AND METHODS: Discussions were held by a group of pediatric urologists and gastroenterologists appointed by the board. The following draft review document was open to all the ICCS members via the ICCS web site. Feedback was considered by the core authors and by agreement, amendments were made as necessary. The final document is not a systematic literature review. It includes relevant research when available as well as expert opinion on the current understanding of therapeutic intervention in congenital neuropatic bladder and bowel dysfunction in children. RESULTS: Guidelines on pharmalogical and surgical intervention are presented. First the multiple modalities for intervention that do not involve surgical reconstruction are summarized concerning pharmacological agents, medical devices, and neuromodulation. The non-surgical intervention is promoted before undertaking major surgery. Indicators for non-surgical treatments depend on issues related to intravesical pressure, upper urinary tract status, prevalence of urinary tract infections, and the degree of incontinence. The optimal age for treatment of incontinence is also addressed. This is followed by a survey of specific treatments such as anticholinergics, botulinum-A toxin, antibiotics, and catheters. Neuromodulation of the bladder via intravesical electrical stimulation, sacral nerve stimulation, transcutaneous stimulation, and biofeedback is scrutinized. Then follows surgical intervention, which should be tailored to each individual, based on careful consideration of urodynamic findings, medical history, age, and presence of other disability. Treatments mentioned are: urethral dilation, vesicostomy, bladder, augmentation, fascial sling, artificial urinary sphincters, and bladder neck reconstruction and are summarized with regards to success rates and complications. Finally, the treatment on neuropathic bowel dysfunction with rectal suppositories irrigation and transrectal stimulation are scrutinized.

The management of adolescents with neurogenic urinary tract and bowel dysfunction.

Most children with neurogenic bladder dysfunction arrive into adolescence with reasonably managed lower urinary tract function only to experience bladder and kidney function deterioration after puberty. The aim of this article is to identify issues that contribute to adverse changes in bladder and renal function during adolescence and to highlight strategies to preserve urinary tract integrity, social continence, patient autonomy, and independence. Surveillance of bladder function requires patient attendance at review appointments and compliance with treatment plans. While encouraging independence and treatment compliance the clinician also needs to consider altered mental concentrating ability and fine motor skills of these patients. A keen eye for imminent loss of patient compliance to treatment protocol should be the mainstay of each encounter during puberty and adolescence. Annual surveillance of adolescent neurogenic bladder patients facilitates early identification of risk factors for urinary tract deterioration. Investigations include renal and bladder ultrasonography, urodynamic study when indicated, substantiated by videocystometry when anatomical status dictates. Serum creatinine should be measured and renal scintigraphy performed when upper urinary tract dilation, renal scarring, or atrophy are suspected. Optimal management of adolescents with neurologic disease of the urinary tract included strategies to reduce elevated detrusor pressure, maintain bladder compliance, and maximize dryness. Antimuscarinic medications, botulinum toxin A, and surgical procedures are enhanced by bowel management regimens and regular nurse or urotherapist patient contact. Caring for the patient as a whole requires discussion of sexuality, fertility status, and behaviors that increase the risk of progressive urinary tract damage.

Compensatory enlargement of a solitary functioning kidney during fetal development.

OBJECTIVE: To determine the degree of compensatory enlargement, and its time of onset, of the solitary functioning kidney (SFK) in fetuses with unilateral renal agenesis (URA) or unilateral multicystic kidney dysplasia (MCKD). METHODS: This was a retrospective study of fetuses with URA or MCKD diagnosed prenatally and confirmed postnatally in the period from January 1999 to May 2011. Fetuses with any other congenital anomalies were excluded. Measurements of kidney length were retrieved from our prenatal ultrasound database and a nomogram was established and compared with that for normal kidney length. RESULTS: In total, 67 fetuses were identified, 60 with MCKD and seven with URA, for which we obtained 147 kidney length measurements from our database. Mean gestational age at time of measurement was 29.7 (range, 18.4-36.7) weeks. Compensatory enlargement, defined as renal length >95(th) percentile for gestational age, was demonstrated in 87% of the MCKD cases and 100% of the URA cases (88% of cases overall). We estimated the mean enlargement for an SFK (defined as difference from 50(th) percentile for normal renal length) at 36 weeks' gestation to be 23.1% (9.25 mm), with the mean value being 11.4% (5.04 mm) greater than the 95(th) percentile for a normal kidney at this gestational age. Compensatory enlargement of SFKs was evident from the 20(th) week of gestation onwards. CONCLUSION: Compensatory enlargement of SFKs occurs in almost 90% of fetuses with MCKD or URA, and may be observed from the 20(th) week of gestation onwards.

Size and volume charts of fetal kidney, renal pelvis and adrenal gland.

OBJECTIVE: To establish reference curves for size and volume of the fetal kidney, renal pelvis and adrenal gland, as measured using ultrasound from the 15(th) week of gestation. METHODS: This was a prospective, longitudinal study of 96 fetuses in low-risk singleton pregnancies, in which we performed serial ultrasound examinations at 4-week intervals. The length and anteroposterior and transverse diameters of both kidneys, the anteroposterior and transverse diameters of the renal pelvises and the length of the adrenal glands were measured three times at each examination, with the average being used for further analysis. Reference charts were constructed using multilevel statistical analysis and comparisons were made with previously published charts derived from cross-sectional data. RESULTS: We present nomograms for fetal kidney dimensions and volume, renal pelvis dimensions and adrenal gland length. The new charts show differences in shape and have narrower percentile bands in comparison to previously published reference ranges. CONCLUSIONS: These new charts of measurements of the fetal kidney, renal pelvis and adrenal gland, from a prospective, longitudinal study, may be useful in the diagnosis and assessment of pathology of the kidney and adrenal gland.

Brain and ventricular volume in patients with syndromic and complex craniosynostosis.

PURPOSE: Brain abnormalities in patients with syndromic craniosynostosis can either be a direct result of the genetic defect or develop secondary to compression due to craniosynostosis, raised ICP or hydrocephalus. Today it is unknown whether children with syndromic craniosynostosis have normal brain volumes. The purpose of this study was to evaluate brain and ventricular volume measurements in patients with syndromic and complex craniosynostosis. This knowledge will improve our understanding of brain development and the origin of raised intracranial pressure in syndromic craniosynostosis. METHODS: Brain and ventricular volumes were calculated from MRI scans of patients with craniosynostosis, 0.3 to 18.3 years of age. Brain volume was compared to age matched controls from the literature. All patient charts were reviewed to look for possible predictors of brain and ventricular volume. RESULTS: Total brain volume in syndromic craniosynostosis equals that of normal controls, in the age range of 1 to 12 years. Brain growth occurred particularly in the first 5 years of age, after which it stabilized. Within the studied population, ventricular volume was significantly larger in Apert syndrome compared to all other syndromes and in patients with a Chiari I malformation. CONCLUSIONS: Patients with syndromic craniosynostosis have a normal total brain volume compared to normal controls. Increased ventricular volume is associated with Apert syndrome and Chiari I malformations, which is most commonly found in Crouzon syndrome. We advice screening of all patients with Apert and Crouzon syndrome for the development of enlarged ventricle volume and the presence of a Chiari I malformation.