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1.

Background

Maternal trauma complicates pregnancy in approximately 7%. Long-term development of children exposed to maternal trauma is unknown.

Aim

To determine neurobehavioural outcome of children (6–18 years) born after maternal trauma in pregnancy compared to a matched control group.

Study design

Case-control study performed at a tertiary medical centre.

Subjects

All consecutive children born after maternal hospitalization for trauma during pregnancy between 1995 and 2005. Controls were children born at the same hospital and period after an uneventful pregnancy.

Outcome measures

Trauma type and severity (Injury Severity Score, ≥9: severe); information from medical files at admission (cases). All mothers filled out two questionnaires about the infant; 1. concerning health, motor development and educational level, 2. concerning behavioural development through the validated Dutch version of the Child Behavior Checklist (CBCL).

Results

Questionnaires were returned by 34 cases and 28 controls. The traumas concerned mainly motor vehicle accidents and falls, and 3/34 had severe injuries. No differences in health, motor development, educational level and CBCL was found between the cases and controls, except for more hospitalization in the cases (p = 0.009).

Conclusion

Long-term follow-up of a limited population of children 6–18 years after exposure of mainly non-severe trauma before birth is similar to a control population except for unexplained more hospitalization in the cases.  相似文献   

2.

Aim

Attention deficit and compromised motor skills are both prevalent in Neurofibromatosis type 1 (NF1), but the relationship is unclear. We investigated motor function in children with NF1 and in children with Attention Deficit/Hyperactivity Disorder (ADHD), and explored if, in patients with NF1, attention deficit influences motor performance.

Methods

Motor performance was measured using the Movement Assessment Battery for Children (M-ABC) in 71 children (26 with NF1 plus ADHD, 14 with NF1 without ADHD, and 31 with ADHD without NF1) aged 6–12 years.

Results

There was a significant effect of group on motor performance. Both NF1 groups scored below children with ADHD without NF1. Attention performance mediated motor performance in children with ADHD without NF1, but not in children with NF1.

Conclusions

Motor function is not mediated by attention performance in children with NF1. While in ADHD, attention deficit influences motor performance, motor problems in NF1 seem to be independent from attention deficit. This argues for different pathomechanisms in these two groups of developmental disorders.  相似文献   

3.

Rationale

The present study aims: (i) to determine how well developmental milestones at 4, 8, 12 and 24 months may predict IQ at 5–6 years old, (ii) to identify cognitive domains during the first two years that best predict later IQ and (iii) to determine whether children with IQ in the normal range at 5–6 years old may differ from disabled (IQ < 70) and gifted children (IQ > 130) with regard to their early cognitive development.

Method

The main developmental milestones were collected through self-administered questionnaires rated by parents at 4, 8, 12 and 24 months and through parental questionnaires administered by a trained interviewer and questionnaires completed following a medical examination at 12 months. These questionnaires were derived from the Brunet-Lézine Psychomotor Development Scale and they addressed several cognitive domains (gross and fine motor skills, language and socialization).

Results

(i) Developmental milestones predict a substantial part of the later IQ variance from 24 months (R2 ~ 20%). (ii) Early language skills more strongly predict later IQ than the other cognitive domains. (iii) Several cognitive domains, but particularly language skills, predict disabled children at 5–6 years old (from the age of 8 months) and gifted children (from the age of 12 months).

Discussion

The present study provides valuable information for early developmental assessment and could contribute to a better understanding of intellectual development.  相似文献   

4.

Background

The quality of general movements (GMs) has proven to have predictive value for the developmental outcome, but this has not yet been studied in twins.

Aims

Our aim was to analyse the quality of GMs and neurological and developmental outcome in relation to the gestational age (GA), mode of conception and other perinatal risk factors in a group of twins.

Study design

The documentation of twins referred for follow-up in the period from 1998 to 2016 was studied retrospectively. Data concerning the quality of GMs, perinatal risk factors and developmental outcome were analysed.

Subjects

Eighty-nine twin pairs, GA from 24 to 38 weeks (median 35.0; IQR 3), birth weight 670 g–3820 g (median 2323; IQR 645) were included.

Outcome measures

Results of neurological, psychological and speech/language development and school outcome were analysed.

Results

GMs at term age and at three to four months postterm age did not differ with regard to the mode of conception. Preterm birth was significantly related to GMs at three to four months postterm age. At term age, GMs were significantly related to neurological outcome, while at three to four months postterm age, GMs were related to both the neurological and psychological outcome. Difficulties in speech/language development were diagnosed in almost half of the children, more frequently in boys and children with lower Apgar scores.

Conclusion

The study highlights the value of GMs for predicting the developmental outcome in twins and indicates the importance of developmental, especially speech/language, follow-up in twins.  相似文献   

5.

Background

The diagnosis of multiple sclerosis (MS) both in children and adults is based on clinical and magnetic resonance imaging (MRI) features according to the McDonald criteria. Little is known about differences in the presentation between pre-pubertal children, adolescents, and adult patients at disease onset.

Objective

To compare (1) the clinical, cerebrospinal fluid (CSF), and MRI characteristics, and (2) the diagnostic performance of the 2010 McDonald criteria between pre-pubertal, adolescent, and adult patients with a clinically isolated syndrome (CIS).

Methods

We performed a retrospective analysis of the initial brain and spinal cord MRI scans from 11 pre-pubertal children, 46 adolescents, and 56 adults with a CIS. Furthermore, clinical, CSF characteristics, and the performance of the 2010 McDonald criteria were compared.

Results

The first inter-attack interval tended to increase with age. With respect to MRI presentation, significantly fewer pre-pubertal children presented with juxtacortical and callosal lesions. We found no significant differences in the fulfillment of the 2010 McDonald criteria between the groups.

Conclusion

In this retrospective series, subtle differences between children, adolescents, and adults with a CIS were noted. Larger samples are required in order to establish distinct features of the different age groups.  相似文献   

6.
Cochlear implants for sensorineural deafness in children is one of the most successful neuromodulation techniques known to relieve early chronic neurodisability, improving activity and participation. In 2012 there were 324,000 recipients of cochlear implants globally.

Aim

To compare cochlear implant (CI) neuromodulation with deep brain stimulation (DBS) for dystonia in childhood and explore relations between age and duration of symptoms at implantation and outcome.

Methods

Comparison of published annual UK CI figures for 1985–2009 with a retrospective cohort of the first 9 years of DBS for dystonia in children at a single-site Functional Neurosurgery unit from 2006 to 14.

Results

From 2006 to 14, DBS neuromodulation of childhood dystonia increased by a factor of 3.8 to a total of 126 cases over the first 9 years, similar to the growth in cochlear implants which increased by a factor of 4.1 over a similar period in the 1980s rising to 527 children in 2009. The CI saw a dramatic shift in practice from implantation at >5 years of age at the start of the programme towards earlier implantation by the mid-1990s. Best language results were seen for implantation <5 years of age and duration of cochlear neuromodulation >4 years, hence implantation <1 year of age, indicating that severely deaf, pre-lingual children could benefit from cochlear neuromodulation if implanted early. Similar to initial CI use, the majority of children receiving DBS for dystonia in the first 9 years were 5–15 years of age, when the proportion of life lived with dystonia exceeds 90% thus limiting benefits.

Conclusion

Early DBS neuromodulation for acquired motor disorders should be explored to maximise the benefits of dystonia reduction in a period of maximal developmental plasticity before the onset of disability. Learning from cochlear implantation, DBS can become an accepted management option in children under the age of 5 years who have a reduced proportion of life lived with dystonia, and not viewed as a last resort reserved for only the most severe cases where benefits may be at their most limited.  相似文献   

7.

Objective

To evaluate prospectively the effectiveness of cognitive behavioral therapy (CBT) in children with autism spectrum disorder (ASD).

Methods

Drug-naïve children who met the DSM-V criteria for a diagnosis of ASD were recruited from a day care center, specialized in long-term treatment of children and adolescents with ASD. Symptom assessment was performed using the Aberrant Behavior Checklist (ABC) before (base-line) and after 12 months (follow-up) of CBT.

Results

Nine boys with a mean age of 6 (±2.0) years were included. Compared to baseline, significant improvements of symptoms of irritability (p = 0.012), hyperactivity (p = 0.008) and lethargy (p = 0.008) were observed at follow-up.

Conclusion

Results indicate that CBT is an effective therapy for children with ASD. Larger studies are needed to give more details about which symptoms respond best in these patients.  相似文献   

8.

Background

While many individuals with severe developmental impairments learn to communicate with augmentative and alternative communication (AAC) devices, a significant number of individuals show major difficulties in the effective use of AAC. Recent technological innovations, i.e., eye-tracking technology (ETT), aim to improve the transparency of communication and may also enable a more valid cognitive assessment.

Objectives

To investigate whether ETT in forced-choice tasks can enable children with very severe motor and speech impairments to respond consistently, allowing a more reliable evaluation of their language comprehension.

Methods

Participants were 17 girls with Rett syndrome (M = 6:06 years). Their ability to respond by eye gaze was first practiced with computer games using ETT. Afterwards, their receptive vocabulary was assessed using the Peabody Picture Vocabulary Test-4 (PPVT-4). Target words were orally presented and participants responded by focusing their eyes on the preferred picture.

Results

Remarkable differences between the participants in receptive vocabulary were demonstrated using ETT. The verbal comprehension abilities of 32% of the participants ranged from low-average to mild cognitive impairment, and the other 68% of the participants showed moderate to severe impairment. Young age at the time of assessment was positively correlated with higher receptive vocabulary.

Conclusions

The use of ETT seems to make the communicational signals of children with severe motor and communication impairments more easily understood. Early practice of ETT may improve the quality of communication and enable more reliable conclusions in learning and assessment sessions.  相似文献   

9.

Background

Cerebral palsy (CP) is a disorder of motor function often accompanied by cognitive impairment. There is a paucity of research focused on cognition in dyskinetic CP and on the potential effect of related factors.

Aim

To describe the cognitive profile in dyskinetic CP and to assess its relationship with motor function and associated impairments.

Method

Fifty-two subjects with dyskinetic CP (28 males, mean age 24 y 10 mo, SD 13 y) and 52 typically-developing controls (age- and gender-matched) completed a comprehensive neuropsychological assessment. Gross Motor Function Classification System (GMFCS), Communication Function Classification System (CFCS) and epilepsy were recorded. Cognitive performance was compared between control and CP groups, also according different levels of GMFCS. The relationship between cognition, CFCS and epilepsy was examined through partial correlation coefficients, controlling for GMFCS.

Results

Dyskinetic CP participants performed worse than controls on all cognitive functions except for verbal memory. Milder cases (GMFCS I) only showed impairment in attention, visuoperception and visual memory. Participants with GMFCS II–III also showed impairment in language-related functions. Severe cases (GMFCS IV–V) showed impairment in intelligence and all specific cognitive functions but verbal memory. CFCS was associated with performance in receptive language functions. Epilepsy was related to performance in intelligence, visuospatial abilities, visual memory, grammar comprehension and learning.

Conclusion

Cognitive performance in dyskinetic CP varies with the different levels of motor impairment, with more cognitive functions impaired as motor severity increases. This study also demonstrates the relationship between communication and epilepsy and cognitive functioning, even controlling for the effect of motor severity.  相似文献   

10.

Objective

To evaluate relationships between whole blood (B-Al) and hair aluminum (H-Al) levels in healthy infants and their immunization history and development.

Methods

We conducted a cross-sectional study of 9- to 13-month-old children recruited from an urban primary care center, excluding those with a history of renal disease or receipt of either aluminum-containing pharmaceuticals or parenteral nutrition. Aluminum levels were measured using inductively coupled plasma-mass spectrometry. Correlation with Bayley Scales of Infant and Toddler Development, Third Edition (BSID) and vaccine-related aluminum load was assessed via linear regression models.

Results

The median age of 85 participants was 287 days. B-Al (median, 15.4 ng/mL; range, 0.9–952 ng/mL) and H-Al (median 42,542 ng/g; range, 2758–211,690 ng/g) were weakly correlated (Spearman ρ = 0.26; P = .03). There was no significant correlation between B-Al or H-Al and estimated aluminum load from vaccines. B-Al was not correlated with BSID composite or subscale scores. Although H-Al was not correlated with BSID scores in models including all data (n = 85), it was inversely correlated with motor composite (P < .02; Wald = 5.88) and the gross motor subscale (P = .04; Wald = 4.38) in models that excluded an extreme outlying H-Al value.

Conclusions

Infant B-Al and H-Al varied considerably but did not correlate with their immunization history. Likewise, there was no correlation between B-Al and infant development or between H-Al and language or cognitive development. An inverse correlation between H-Al and BSID motor scores deserves further investigation.  相似文献   

11.
Children with cerebral palsy display disorders in pelvic movement and require effective rehabilitation. There is evidence to support the hippotherapy due to improvements in balance. The aim of this narrative review was to summarise the grades of recommendation regarding the benefits of hippotherapy in children with cerebral palsy.

Data sources and extraction

We searched electronic databases, limiting the searches to studies published between 2004 and February 2017. The selected documents were classified according to the strength of recommendation provided by Duodecim (the Finnish medical society). The methodological quality of the selected studies was evaluated using the PEDro scale.

Results

18 studies (four graded A, eight graded B and six graded C) showed clinical changes in the outcomes of gross motor function, sitting independently, speed of walking, length of stride and postural alignment of the head in children with cerebral palsy. Study quality was poor to good (mean PEDro Score of 6 out of 10). Benefits were identified in relation to psychological factors, as well as positive effects on quality of life and the performance of daily life activities.

Conclusions

Gains were also observed in postural alignment and the balance of head and trunk. Moreover, there were improvements in quality of life and the activities of daily life, such as jumping, balance, strength and ascending and descending stairs.  相似文献   

12.

Context

Dissociative disorders present a huge challenge in clinical settings. In contrast to other dissociative symptoms, dissociative sensibility disorders are rarely focused on.

Objective

To identify the clinical characteristics and outcomes of dissociative sensibility disorders in children and adolescents, and to review the use of diagnostic procedures.

Data sources

For the review, a literature search used Pubmed, Embase, Web of Science, and PubPsych (to 02/2015) and the reference lists of the studies identified.

Study selection

Screening of titles and abstracts; full-text assessment by two reviewers.

Data selection

The original case series was identified by using the local data register.

Data extraction

Two reviewers independently reviewed the data and, if they agreed on the relevance, extracted the data. In the original case series, data were extracted retrospectively from the records.

Results

Sixteen studies and seven case reports were identified, including 931 cases with dissociative disorders. In 210 cases the patient suffered either from a single sensibility disorder or predominantly from sensibility disorders. We identified thirteen further cases in our cohort. In both groups there was female predominance; the mean age of manifestation was early adolescence. The timing of admissions was variable. In approximately 50% of cases a premorbid stressful life event could be identified. Over 75% of cases had a good prognosis with complete resolution.

Limitations

Retrospective character of our own data collection, partially missing differentiation between the subgroups of dissociative disorders in the reviewed studies.

Conclusions

There is no uniform procedure for diagnostic work-up. The overall short-term prognosis is good.  相似文献   

13.

Background

Developmental Coordination Disorder (DCD) is a neurodevelopmental disorder that involves difficulties in goal-directed motor coordination, with ineffective control of fine and gross motor movements in the absence of sensory impairment or neurological condition. DCD is frequently reported in children born very preterm (VP) who survive without CP.

Aims

To measure the risk of DCD at school age in a large area-based cohort of VP children and general population controls, adjusting for gender, birth weight by gestational age and age at assessment.

Methods

VP children (N = 608) were part of a prospective cohort study in Italy. Controls (N = 370) were participants in the DCDQ-Italian validation study in the same age range. The Italian version of Developmental Coordination Disorder Questionnaire (DCDQ-Italian) was used to measure the performances in motor coordination during ordinary activities from the parental point of view. Multivariable regression analysis was used to obtain adjusted risk ratios of screening positive for DCD.

Results

VP children had scores significantly lower than peers, and about 30% of them appeared at risk of DCD using the 15th percentile cut-off of the Italian validation study. Birth-weight <10th percentile for gestational age and male gender were significant predictors. A slight trend effect was present, with extremely preterm children (<28 weeks gestation) showing the highest risk.

Conclusions

Our study confirmed the higher DCD risk in VP children, particularly when males and SGA.  相似文献   

14.

Introduction

Surgery in children can be difficult for patients and parents. We aimed to summarize pediatric patients' and parents' psychosocial experiences and needs in surgery.

Method

We used the Ovid search engine and screened 877 abstracts across three databases to extract data on pediatric patients' and parents' surgical experiences.

Results

Our search yielded 11 eligible studies representing 1,307 children undergoing surgery and their parents. Children's adverse experiences included psychological and behavioral changes before, during, and after surgery (e.g., anxiety, eating disturbances). Parents commonly experienced psychological distress. Children's needs related to medical and health care services, whereas parents had high information needs.

Discussion

Children's adverse experiences can negatively affect medical outcomes. Children's experiences are inextricably linked to their parents' and can become negatively affected by their parents' adverse experiences. Patients and parents with previous hospitalizations and surgeries had worse surgical experiences, highlighting further research in the context of chronic illness.  相似文献   

15.

Objective

To assess differences in health care access, utilization, and experiences among Latino children in California according to parental citizenship status and language use.

Methods

Data are from the 2011 and 2012 California Health Interview Survey public use child files. A total of 2841 interviews of parents of Latino children younger than the age of 12 years were conducted. Analyses were conducted to determine the associations between access (usual of source of care, delay in receiving needed care, health insurance), utilization (physician visits in past year, emergency department visits), and experiences (doctor listens, doctor explains instructions clearly, communication via telephone or e-mail) according to parental citizenship status and household language use after adjusting for confounders.

Results

In multivariate analyses, there were no significant differences in access to care according to parental citizenship status. Children with 2 noncitizen parents had fewer doctor visits and were less likely to go to the emergency department in the past year than those with 2 citizen parents. Among children with 1 or 2 noncitizen parents, their parents reported worse experiences in care than those with 2 citizen parents. Similar results were observed for language use. Parents of children in bilingual and Spanish-only households were less likely to report that their children's doctors explained things clearly, and parents in Spanish-only households were less likely to communicate via telephone or e-mail than those in English-only households.

Conclusions

Health policy should focus on provider-parent communication to ensure health care equity for Latino children whose parents are not citizens or do not speak English.  相似文献   

16.

Background

Pompe disease (PD) is a rare condition caused by mutations in gene encoding for the enzyme alpha-glucosidase, resulting in an abnormal intracellular accumulation of glycogen. The disease clinical spectrum ranges from severe infantile forms to adult-onset forms with minor limitations. Since 2000 enzyme replacement therapy (ERT) is available and disease natural history has changed, with prolonged survival and evidence of myopathic features.

Methods

In this study, we monitored disease progression up to three years in eight young patients with PD. Based on the literature data and the long term personal experience, we selected validated functional scales for neuromuscular disorders and compared the results to identify a simple and reliable protocol for the follow-up of children with PD. Moreover, we evaluated cognitive functions using developmental/cognitive tests.

Results

Based on study results, we suggest that motor functions in children with PD could be better assessed by Chop Intend, MFM20 (Motor Function Measure Scale for Neuromuscular Diseases 20) and NSAA (North Star Ambulatory Assessment), according to age and functional level. Evaluation should be completed with ROM (Range Of Motion) measurement, MRC (Medical Research Council) evaluation and 6MWT (6 Minute Walk test) when possible.

Conclusions

The proposed protocol seems to be reliable and should be done every six months, because of the progressive natural history of the disease, the rapid changes typical of developmental age and the need to document ERT effects. About cognitive functions, additional tests to classical intelligence scales (WISC, WPPSI) should be useful to better describe specific neuropsychological profile.  相似文献   

17.

Introduction

The purpose of this study was to explore the communication behaviors demonstrated by parents of children with chronic conditions and provider team members when communicating about the child's care in outpatient clinics using concepts from the Theory of Shared Communication (TSC).

Methods

This was a secondary data analysis of 30 previously recorded pediatric clinic visits. Communication among parents and provider team members was analyzed using a researcher-developed coding scheme based on the TSC.

Results

Provider team members dominated communication during clinic visits, showing more frequent use of asking, explaining, advocating, and negotiating behaviors than parents. Parents were engaged in communication with frequent asking, explaining, and advocating behaviors.

Discussion

Parents of children with chronic conditions and multidisciplinary providers demonstrated the communication behaviors of the TSC in an outpatient clinic setting. Provider dominance of communication in the clinic setting may disempower parents and impair relationships.  相似文献   

18.

Background

Long-term follow-up data after different vascular types of ischemic perinatal stroke is sparse. Our aim was to study neurodevelopmental outcomes following neonatal and presumed perinatal ischemic middle cerebral artery territory stroke (arterial ischemic stroke, AIS) and periventricular venous infarction (PVI).

Methods

A prospective consecutive cohort of 40 term-born children with perinatal stroke (21 AIS, 19 PVI) was identified through the Estonian Paediatric Stroke Database. While 48% of the children with AIS were diagnosed during the neonatal period, all the children with PVI had presumed perinatal stroke. Outcomes based on the Paediatric Stroke Outcome Measure (PSOM) and Kaufman Assessment Battery for Children – Second Edition (K-ABC-II), in relation to extent and laterality of stroke, were defined.

Results

At a median age of 7 years 6 months (range 3.6–13y), there was a trend towards worse neurodevelopmental outcome in participants with AIS when compared to PVI (mean total PSOM scores 3.1 and 2.2, respectively; p = 0.06). Combined deficits of motor, language and cognitive/behavioural functions were significantly more common among children with AIS (90%) when compared to children with PVI (53%, p = 0.007). General cognitive ability (by K-ABC-II) was significantly lower in the AIS subgroup (mean 79.6; 95% CI 72.3–87.0), but children with PVI (91.6; 95% CI 85.5–97.8) also had poorer performance than the age-equivalent normative mean. Large extent of stroke was associated with poorer neurodevelopmental outcome and lower cognitive performance in children following AIS but not in PVI.

Conclusion

In this national cohort, poor long-term neurodevelopmental outcome after perinatal ischemic stroke was seen irrespective of the vascular type or time of diagnosis of stroke. However, the spectrum of neurological deficits is different after perinatal AIS and PVI, with combined deficits more common among children following AIS.  相似文献   

19.

Background

In non-walking children with severe spasticity, daily care can be difficult and many patients suffer from pain. Selective dorsal rhizotomy (SDR) reduces spasticity in the legs, and therefore has the potential to improve daily care and comfort.

Aim

To examine effects of SDR on daily care and comfort in non-walking children with severe spasticity due to different underlying neurological conditions.

Methods

Medical history, changes in daily care and comfort and satisfaction with outcome were assessed retrospectively in non-walking children who underwent SDR in our center, with a mean follow-up of 1y 7m (range 11m–4y 3m). All eligible patients (n = 24, years 2009–2014) were included.

Results

Mean age at SDR was 12y 4m (SD 4y 3m, range 2y 8m–19y 3m). Associated orthopaedic problems were frequent. Seven patients underwent scoliosis correction in the same session. Most improvements were reported in dressing (n = 16), washing (n = 12) and comfort (n = 10). Median score for satisfaction was 7 on a scale of 10 (range 1–9). SDR resulted in reduction of spasticity in leg muscles. In nine patients dystonia was recorded post-operatively, mainly in children with congenital malformations and syndromes.

Interpretation

SDR is a single event intervention that can improve daily care and comfort in non-walking children with severe spasticity, and can safely be combined with scoliosis correction. Despite the improvements, satisfaction is variable. Careful attention is necessary for risk factors for dystonia, which may be unmasked after SDR.  相似文献   

20.

Background

Ataxia telangiectasia (AT) is a neurodegenerative cerebellar disorder, caused by mutations in the ATM gene, involved in DNA repair. Radiosensitivity, progressive ataxia, immune deficiency and malignancies, are well known symptoms, but urological manifestations are scarcely described.

Objective

To characterize urologic manifestations in a large cohort of AT patients.

Methods

Retrospective cross-sectional chart study comprising 52 AT patients followed at a National AT Center.

Results

25% of the cohort (13 patients/8 males) had urologic symptoms, which presented at 11 ± 4.3 years. The most common symptom was secondary enuresis affecting 15% of the patients (8 children/4 males). Incontinence appeared at 8 ± 6.2 years of age, and resolved spontaneously within 15 ± 8.3 months in 6 patients. It preceded loss of ambulatory capacity by 1–2 years in 7 patients. Lumbosacral MRI were normal (4 children) and urine cultures (all) were negative. Urodynamic evaluation that was performed in only one patient revealed overactive bladder. Additional manifestations were macroscopic hematuria due to bladder telangiectasia in a 12-year-old, and renal cell carcinoma in a 22-year-old. Other manifestations unrelated to AT were neprolithiasis, vesico-ureteral reflux and scrotal pain, each in 1 patient.

Discussion

Transient secondary enuresis is a frequent finding in AT patients, heralding loss of ambulatory capacity, tough it's pathophysiological mechanism is largely no understood.  相似文献   

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