Emanuele Ausili

Assessment of health status in children with spina bifida

Study design:Prospective multidimensional study by means of: (1) clinical assessment, (2) parental-administered questionnaire for general health (CHQ-PF50), and (3) standardised disability measurements.Objectives:To assess the health-related quality of life (QoL) and disability in children with spina bifida (SB) and to correlate them with the clinical picture and our previous study on adolescents with SB.Setting:SB Centre at a University Hospital in Italy.Methods:A total of 29 consecutive children with SB (mean age 11.4, range 4–14 years)were evaluated through Child Health Questionnaire Parental Form (CHQ-PF50), the FIM instrument, and the Barthel index.Results:Disability was inversely related only (r=0.49; P=0.007) to the physical aspect of the QoL of children. Similarly, the disability was inversely related (r=0.37; P=0.005) to the emotional aspect of QoL of patients parents. Unexpectedly, for the mental aspects of QoL of patients, major disability was not associated with higher psychological distress and severe role disability due to emotional problems. At clinical examination, findings especially for continence and number of catheterisations were usually related to deterioration of physical aspects of QoL (r=−2.28; P=0.02) in children.Conclusion:The multiperspective assessment showed that there is a linear inverse correlation between disability and QoL in children with SB only for physical aspects. Conversely, there is linear inverse correlation between disability and QoL in patients parents regarding only emotional aspects. Moreover, this study provided useful information for clinical practice underlining that continence problems are those that most affect QoL in children with SB and their parents.

Polyethylene glycol 4000 vs. lactulose for the treatment of neurogenic constipation in myelomeningocele children: a randomized‐controlled clinical trial

Aim  To compare the therapeutic effectiveness and tolerability of low daily doses of polyethylene glycol 4000 vs. lactulose in the treatment of neurogenic constipation in children with myelomeningocele.

Transanal irrigation in myelomeningocele children: an alternative, safe and valid approach for neurogenic constipation

Study design:A total of 60 children with myelomeningocele referred to Spina Bifida Center of Rome (31 boys and 29 girls; aged 8–17 years) were treated with transanal irrigation for three months.Objective:To investigate whether transanal irrigation is a valid and alternative approach for neurogenic constipation in children with myelomeningocele.Methods:A questionnaire on bowel disturbances, quality of life and side effects was completed before the beginning and at the termination of the study.Setting:ItalyResults:About 60% (36/60) of patients reported relief from constipation and 75% (12/16) for fecal incontinence. Wheelchair-bound and walking patients showed same high improvement of bowel habit. Mean (s.d.) scores before and after the study were: neurogenic bowel dysfunction total score: 17.5 (5.2) versus 8.5 (4.3) (P<0.001); digital stimulation of anorectum: 4.2 (2.8) versus 1.3 (2.5) (P<0.01); frequency of fecal incontinence: 5.5 (1.2) versus 1.3 (1.7) (P<0.01) and degree of general satisfaction: 3.0 (2.4) versus 7.7 (1.5) (P<0.001).We observed a reduction of urinary tract infections during the course of treatment: 14 total urinary tract infections (9 caused by Escherichia coli) before versus 6 (3) during treatment (P<0.01)Conclusion:Transanal irrigation in children with myelomeningocele is an alternative and relatively safe approach for managing neurogenic constipation; in fact, it improves bowel disturbances, quality of life and seems to reduce the risk of urinary tract infections.

Bone mineral density in survivors of childhood brain tumours

BackgroundOsteopenia has been reported in children surviving acute lymphoblastic leukaemia, apparently as consequence of therapy. Few studies have been published on bone mineral density (BMD) evaluation in children surviving from brain tumours. The endocrine system in these patients is frequently affected as consequence of therapeutic interventions such as cranial irradiation and anti-neoplastic agents: growth hormone deficiency is the most common adverse sequel. The pathogenesis of osteopenia in brain cancer survivors is multi-factorial but still uncertain.ObjectiveThe aim of this study is to examine bone mass in 12 brain cancer survivors and its relationship with their hormonal status.Results and discussionWe observed that most of the patients had a BMD that was lower than normal in both the lumbar column and in the femoral neck. Bone mass loss was higher in the lumbar region rather than in the femoral neck, due to spinal radiation therapy and to the effect of hormonal deficiencies. Particularly hypogonadism, but also multiple hormonal deficiencies, are associated with lower BMD values. Experience in clinical care of these patients suggests the importance of periodic evaluations of BMD, especially in those with secondary hormone deficiencies. Moreover, the periodic assessment of the hypothalamus–pituitary function is essential for an early diagnosis of hormonal insufficiency, primarily hypogonadism, to precociously detect bone mineral loss and to prevent pathological fractures, thus improving the quality of life.

Sublingual desensitization in children with congenital malformations and latex allergy

The frequency of latex allergy in children requiring multiple surgery ranges from 16.7% to 65%. The aim of this study was to investigate the safety and efficacy of latex desensitization in a group of 10 patients with a history of multiple surgical procedures and clinically manifested allergy to latex. We selected 10 children (female–male ratio = 5:5), aged 4–16 yr (mean ± s.d.: 9 ± 4), with a history of multiple surgical procedures, adverse reactions to latex and positive skin test to latex and/or specific immunoglobulin E (IgE). Latex allergy diagnosis was confirmed by specific provocation tests (cutaneous, sublingual, mucous, conjunctival tests). Rush (4‐day) sublingual desensitization was performed with increasing doses of latex extract (ALK Abellò) under patients’ tongue until the highest dose of 500 μg of latex. A maintenance therapy (10 drops of undiluted solution three times a week) was recommended. During the 2‐yr follow‐up mean values of specific IgG4 and IgE, eosinophilic cationic protein and total IgE did not show significant variations. Patients did not manifest any adverse effect during the rush phase and only two patients manifested mild local symptoms during the maintenance therapy. All the challenges showed a reduction in terms of percentage of positivity and mean scores. All the patients showed a reduction of the mean individual score (p < 0.001). Furthermore patients who needed dental examination or surgery underwent such procedures without the occurrence of symptoms. Our preliminary results show sublingual desensitization to latex can be an important therapeutic tool in the management of young allergic patients requiring multiple operations.

Peristeen(®) transanal irrigation in paediatric patients with anorectal malformations and spinal cord lesions: a multicentre Italian study.

In paediatric and adult patients with neurogenic bowel, transanal irrigation (TAI) of the colon has gained popularity due to the introduction of a specifically designed device. The aim of this pilot study was to present the results of TAI using the Peristeen® TAI system in a group of paediatric patients with anorectal malformation (ARM) and congenital or acquired spinal cord lesions (SCLs).

The prevalence of small intestinal bacterial overgrowth and methane production in patients with myelomeningocele and constipation

Study design:Prospective study.Objectives:The objective of this study was to assess the prevalence of small intestinal bacterial overgrowth (SIBO), methane (CH4) production and orocecal transit time (OCTT) in children affected by myelomeningocele.Setting:This study was conducted at the Catholic University in Rome, Italy.Methods:Eighteen (6M/12F; 16.4±7.6 years) children affected by myelomeningocele were enrolled. All subjects underwent H2/CH4 lactulose breath tests to assess SIBO and OCTT. All patients performed a visual analog scale to investigate abdominal pain, bloating and flatulence, and maintained a diary of the frequency and consistency of the stool during the previous 7 days. A nephro-urological clinical evaluation of the number of urinary tract infections (UTIs) and neurogenic bowel disease score were also performed.Results:Thirty-nine percent (7/18) of the children showed SIBO and 61% (11/18) presented a delayed OCTT. Moreover 44.4% (8/18) produced high levels of CH4. Interestingly, all myelomeningocele children who produced CH4 showed a delayed OCTT and a higher incidence of UTI, with a lower frequency of evacuation, compared with those with a normal or accelerated OCTT.Conclusion:The association between CH4 and constipation suggests that CH4 has an active role in the development of constipation. One of the most interesting features of our study is to identify a correlation between myelomeningocele, CH4, delayed OCTT and UTI. The intestinal decontamination with locally acting drugs in these children may reduce the number of UTIs and improve intestinal motility.

GDNF PLASMA LEVELS IN SPINA BIFIDA: CORRELATION WITH SEVERITY OF SPINAL DAMAGE AND MOTOR FUNCTION

Glial-derived neurotrophic factor (GDNF) is one of several powerful survival factors for spinal motoneurons that play a key role in sprouting, synaptic plasticity, and reorganization after spinal cord damage. The aim of this study was to investigate the expression of GDNF in plasma of children with spina bifida (SB) and to determine its correlation with both the severity of spinal cord damage and the motor function of these patients. To measure the GDNF expression, we collected plasma samples from 152 children with SB and in 149 matched controls. Endogenous GDNF levels were quantified using a two-site immuno-enzymatic assay. The statistical analysis was performed using the Mann-Whitney two-tailed two-sample test. In children with SB the mean levels of GDNF (131.2 +/- 69.6 pg/mL) were significantly higher (p < 0.001) with respect to the mean levels of the control group (102.7 +/- 6.8 pg/mL). Moreover, in open SB, the GDNF levels (139.2 +/- 81.1 pg/mL) were significantly higher (p < 0.05) with respect to closed SB (117.2 +/- 41.3 pg/mL). In terms of the motor function of patients, we found that in children with poorer motor function, the GDNF levels (134.5 +/- 67.4 pg/mL) were higher, but not statistically significant (p < 0.1), than in patients with better motor outcome (122.3 +/- 72.2 pg/mL). Our study demonstrates GDNF over-expression in children with SB. This upregulation is significantly associated with the severity of spinal cord damage in SB patients and appears to correlate with poor motor function of children, representing an important biochemical marker of the severity of spine injury.

Analytical assessment of bone serum markers in patients suffering from spina bifida

Neural tube defects are serious abnormalities that occur early in embryonic development and result from failure of the neural tube to close properly in the developing brain and/or lower spine. These defects include anencephaly, myelomeningocele (MMC) (commonly called spina bifida [SB]) and encephalocele. In SB patients there is also a spectrum of impairments, such as lower limb paralysis and sensory loss, bladder and bowel dysfunction, cognitive damaging and is often associated with Arnold-Chiari type II malformation; hydrocephalus; and are at increased risk for fractures [1, 2]. In the US, each year, about 1500 babies are born with SB and across Europe, and an estimated 4500 pregnancies are affected by NTDs [3, 4]. Etiology is multifactorial and is the result of a combination of genetic and environmental factors, such as use of certain anticonvulsants, maternal diabetes, and maternal folic acid deficiency. The aim of the present study is to assess bone formation and resorption in patients with SB and risk factors related to this pathology. Since the regulation of plasma calcium levels is crucial for neural transmission, normal cell function, bone structure and intracellular signaling, and due to the interactions among parathyroid glands, thyroid gland and vitamin D, we planned to evaluate blood calcium and phosphorus content along with: 1) parathyroid hormone (PTH), that increases bone resorption and the release of plasma Ca2+ into the circulation and stimulates the hydroxylation of vitamin D; 2) osteocalcin, which is a marker of skeletal bone turnover; 3) vitamin D, that regulates bone resorption and formation and suppresses the synthesis and release of PTH, also acting as an important mediator of innate and adaptive immune responses. The awareness of a role for vitamin D in the regulation of immune system was triggered by the discovery of vitamin D receptors (VDRs) in almost all immune cells. Moreover, it inhibits the expression of inflammatory cytokines in monocytes [5]; thyroid stimulating hormone (TSH), triiodothyronine (FT3) and tetraiodothyronine (FT4) essential for bone growth and development through activation of osteoclast and osteoblast activities. For these reasons, Vitamin D status could be very important as factor reducing co-morbidities in SB patients. In the Spina Bifida Centre of Catholic University, Rome, a team of physicians collected detailed medical history and performed a careful clinical examination. Medullar and brain magnetic resonance imaging were acquired. Written informed consent was obtained from each subject before inclusion. The study included 78 patients, 33 male and 45 female, aged 1–29 years, and 34 healthy subjects, 13 male and 21 female, aged 1–31 years. Patients were grouped on the basis of the type of lesions, as follows: 1) not ulcerated MMC; 2) ulcerated MMC; and 3) lipomeningomyelocele (LMC). Moreover, the presence of hydrocephalous and Arnold-Chiari II syndrome was pointed out. Neurological impairment was classified in three categories: patients having dorsal, lumbosacral, and sacral involvement. The ambulatory status of patients was clustered into three groups, defined as follows: 1) Individuals who did not *Corresponding author: Dr. Krizia Pocino, Institute of Biochemistry and Clinical Biochemistry, Largo A. Gemelli 8, 00168 Rome, Italy, E-mail: krizia.pocino@gmail.com Claudia Rendeli, Emanuele Ausili and Valentina Paolucci: Spina Bifida Center, Department of Pediatrics, Policlinico Universitario A. Gemelli, Rome, Italy Costantino Romagnoli: Division of Neonatology, Department of Pediatrics, Policlinico Universitario A. Gemelli, Rome, Italy Cinzia Carrozza and Ettore Capoluongo: Institute of Biochemistry and Clinical Biochemistry, Policlinico Universitario A. Gemelli, Rome, Italy

Prenatal diagnosis, natural history, postnatal treatment and outcome of 222 cases of spina bifida: experience of a tertiary center: Prenatal diagnosis and long-term outcome of 222 cases of fetal Spina Bifida

To report on the prenatal ultrasonographic diagnosis of spina bifida (SB) and its natural history, treatment and long‐term outcome in a large tertiary referral center.