Wednesday, October 31, 2007

Appendicostomy stomas and antegrade colonic irrigation after laparoscopic antegrade continence enema

Kim J, Beasley SW, Maoate K. Appendicostomy stomas and antegrade colonic irrigation after laparoscopic antegrade continence enema. Journal of Laparoendoscopic & Advanced Surgical Techniques 2006 Aug;16(4):400-3.

BACKGROUND: Children with spina bifida, high anorectal anomalies, or neuronal intestinal dysplasia who are treated with a laparoscopic antegrade continence enema to achieve a socially acceptable level of fecal continence sometimes have problems with the stoma and its catheterization. The goal of this study was to determine the nature and incidence of these problems, and their relationship to the underlying condition.

MATERIALS AND METHODS: A retrospective review of the hospital case notes of 74 consecutive patients who had a laparoscopic antegrade continence enema was undertaken.

RESULTS: The laparoscopic antegrade continence enema procedure is well tolerated but is associated with a variety of usually minor complications including stomal stenosis, leakage, peristomal infection, granulation tissue overgrowth, mucosal prolapse, abdominal discomfort during irrigation, appendiceal false passage, and ineffective irrigation. Surgical revision of the stoma was required in 19% of the cases in this study, usually because of stenosis and skin overgrowth. Ongoing problems achieving colonic emptying were most likely to occur in patients with an anorectal malformation.

CONCLUSION: Overall, the laparoscopic antegrade continence enema provides an effective method of facilitating emptying of the bowel. However, it has a high incidence of minor troublesome problems, with stenosis and skin overgrowth of the stoma being the most common. Younger children tend to have more complications and difficulty performing effective irrigation. Children with anorectal malformations were more likely to require surgical revision of the stoma, and often needed ongoing manual evacuation and bowel washouts despite the laparoscopic antegrade continence enema.

PMID: 16968193

Achieving Fecal Continence in Patients With Spina Bifida: A Descriptive Cohort Study

Velde SV, Biervliet SV, Renterghem KV, Laecke EV, Hoebeke P, Winckel MV. Achieving Fecal Continence in Patients With Spina Bifida: A Descriptive Cohort Study. Journal of Urology. 2007 Oct 16; [Epub ahead of print]

PURPOSE: Fecal incontinence is a major problem in patients with myelomeningocele. We evaluate the results of a stratified approach aimed at obtaining fecal pseudo-continence in patients with myelomeningocele.

MATERIALS AND METHODS: We conducted a cross-sectional descriptive study of last file data in 80 patients 5 to 18 years old with myelomeningocele followed at our center. Beginning at birth patients with myelomeningocele were seen at least annually by the pediatric gastoenterologist, a member of the multidisciplinary "spina team." Constipation was treated with diet and osmotic laxatives. Starting at age 5 years, treatment was targeted at achieving pseudo-continence. A toilet training scheme was started, associated with induced defecation by digital stimulation. Retrograde tap water enemas were used in patients with unsatisfactory results. If retrograde enemas were unsuccessful, an antegrade continence enema procedure was proposed. For children unable to sit on a toilet regular manual evacuation of stools was advised.

RESULTS: Eight of the 80 patients were fecal continent. Pseudo-continence was achieved in 50 of the 72 incontinent patients (69%), including 5 of 5 following only a strict toilet scheme, 21 of 24 (87.5%) performing retrograde enemas, 16 of 20 (80%) performing orthograde enemas through an antegrade continence device and 8 of 10 performing regular manual evacuation of stools. In 4 of the 20 patients (20%) performing orthograde enemas complications led to closure of the antegrade continence device. Treatment failed and was stopped in 17 patients. Success of treatment was not related to level of spinal lesion or degree of mobility.

CONCLUSIONS: Fecal pseudo-continence was achieved in 58 of 80 patients (72.5%) with myelomeningocele.

PMID: 17945290

Antegrade and retrograde endoscopic dextranomer/hyaluronic Acid bladder neck

Dean GE, Kirsch AJ, Packer MG, Scherz HC, Zaontz MR. Antegrade and retrograde endoscopic dextranomer/hyaluronic Acid bladder neck bulking for pediatric incontinence. Journal of Urology. 2007 Aug;178(2):652-5. Epub 2007 Jun 15.

PURPOSE: Endoscopic bladder neck bulking techniques offer the potential for a relatively noninvasive cure for a difficult clinical problem. We review our experience using antegrade and retrograde approaches.

MATERIALS AND METHODS: A total of 34 children (18 boys and 16 girls, mean age 11.7 years) have been treated since March 2003. Of the patients 28 (82%) had neurogenic bladder and 6 had nonneurogenic sphincteric incontinence. Urodynamics confirmed low detrusor leak point pressures and adequate bladder capacity. Patients were treated with either a retrograde or an antegrade approach. In 82% of patients an antegrade approach was used and a posttreatment suprapubic tube was placed.

RESULTS: Mean followup was 11.7 months (range 3 to 31). Patients averaged 1.47 injections (range 1 to 5). Detailed followup of 19 patients revealed significant improvement in continence in 78% (mean 1.6 injections), with an average followup of approximately 1 year.

CONCLUSIONS: Our 31 months of experience with antegrade/retrograde bladder neck bulking demonstrates that it is a viable therapy for this group of children. While some patients have experienced prolonged success, re-treatment can be beneficial. The antegrade approach offers several advantages, including intraoperative leak point pressures, improved visualization and placement of a suprapubic tube to limit post-procedural remodeling.

PMID: 17574622

An assessment of health related quality of life

Dodson JL, Diener-West M, Gerson AC, Kaskel FJ, Furth SL. An assessment of health related quality of life using the child health and illness profile-adolescent edition in adolescents with chronic kidney disease due to underlying urological disorders. Journal of Urology. 2007 Aug;178(2):660-5; discussion 665. Epub 2007 Jun 15.

PURPOSE: We examined health related quality of life in adolescents with congenital urological disease causing kidney disease using a generic health related quality of life instrument. We then compared the results to those in adolescents with medical kidney disease and to population based norms.

MATERIALS AND METHODS: The Child Health and Illness Profile-Adolescent Edition was administered to 113 patients 10 to 18 years old with chronic kidney disease. Mean domain and subdomain scores for adolescents with urological disease were compared to those of adolescents with medical kidney disease and to population based norms.

RESULTS: The cohort included adolescents with an underlying diagnosis of congenital urological anomaly (37 patients) or other causes of kidney disease (76). Compared to adolescents with kidney disease caused by other factors, those with congenital urological disease scored statistically significantly better in the Child Health and Illness Profile-Adolescent Edition subdomain of Limitations of Activity (mean 22.3 [SD 2.5] vs 20.4 [SD 5.0], p = 0.04). Compared to population norms, adolescents with congenital disorders scored lower in the Disorders domain (mean 16.5, 95% CI 14.2 to 18.9) but better in the Risks domain (mean 25.9, 95% CI 25.1 to 26.6) and in the Home Safety and Health subdomain (mean 25.2, 95% CI 23.7 to 26.6).

CONCLUSIONS: As assessed by the Child Health and Illness Profile-Adolescent Edition generic health status questionnaire, adolescents with kidney disease due to underlying congenital urological disease had fewer limitations of activity compared to those with underlying medical kidney disease. Except for low scores in the Disorders domain, children with underlying urological disease did not have significant impairments in any other domain compared to population based norms.

PMID: 17574620

Monday, October 29, 2007

Do grip and pinch strength predict neurologic complications in children with spina bifida and hydrocephalus

Liptak GS, Fried R, Baltus-Hebert E, Eyer Tierney S, Fucile S, Doremus TL. Do grip and pinch strength predict neurologic complications in children with spina bifida and hydrocephalus? Pediatric Neurosurgery. 2006;42(4):208-13.

BACKGROUND: Neurological complications occur commonly in children with meningomyelocele and can cause significant morbidity and mortality. An earlier study suggested that acute changes in grip and pinch strength could be used to identify individuals at increased risk for developing a neurological complication.

OBJECTIVE: To evaluate the use of grip and pinch measurements to screen for neurological problems in children with spina bifida and hydrocephalus.

DESIGN: A prospective evaluation of screening tests.

PATIENTS: 92 children, born since 1976, who had meningomyelocele and hydrocephalus and were treated at the University of Rochester Medical Center.

METHODS: Grip and pinch strength were measured between July, 1991, and June, 2003. RESULTS: Mean grip and pinch strengths were similar to those found in previous studies of children with meningomyelocele; 58 neurological events occurred in 39 (40%) individuals. These included 31 episodes of ventricular shunt failure and 22 symptomatic tethered cord occurrences. Specificity, sensitivity and likelihood ratios were calculated in multiple ways using different criteria for loss of grip or pinch strength and for interval to neurological event. Sensitivities were low (<0.35) and the highest positive likelihood ratio found, using fall in either lateral pinch with 6 months to neurological event, was 2.3.

CONCLUSIONS: Despite previous recommendations, grip and pinch measurements were not helpful when used as a routine screening test for neurological dysfunction for children with meningomyelocele and hydrocephalus.

PMID: 16714860

Seven distinct coexistent cranial and spinal anomalies

Emmez H, Tokgoz N, Dogulu F, Yilmaz MB, Kale A, Baykaner MK. Seven distinct coexistent cranial and spinal anomalies. Pediatric Neurosurgery. 2006;42(5):316-9.

Existence of multiple cranial and spinal anomalies in spina bifida is well known; however, coexistence of seven different severe anomalies is extremely rare. The location of the anomalies, the patient's age and presentation are other interesting aspects of the presented case.

CASE REPORT: A 1-year-old girl with an enlarged head and big, infected lumbosacral myelomeningocele (MMC) was admitted to the emergency department in a comatose state. Further investigations revealed hydrocephalus, Chiari malformation, syringohydromyelia, split cord malformation, dermal sinus tract, lumbosacral MMC, and tethered cord. Unfortunately, the patient died 3 days after admission because of meningitis and sepsis.

DISCUSSION: Coexistence of seven different craniospinal anomalies is extremely unusual. Further investigations with magnetic resonance imaging for associated anomalies, early shunt placement and MMC repair are required to prevent this life-threatening condition in spina bifida.

PMID: 16902346

Spina bifida outcome: a 25-year prospective

Bowman RM, McLone DG, Grant JA, Tomita T, Ito JA. Spina bifida outcome: a 25-year prospective. Pediatric Neurosurgery. 2001 Mar;34(3):114-20.

BACKGROUND: Open spina bifida is the most complex congenital abnormality compatible with long-term survival. This report outlines the 20- to 25-year outcome for our original cohort of patients with a myelomeningocele treated in a nonselective, prospective manner.

METHODS: Of the initial 118 children, 71 patients were available for our most recent review. Nineteen patients have been lost to follow-up and 28 patients have died. Data were collected on: motor level, shunt status, education/employment, seizure history, mobility, bladder/bowel continence, tethered cord, scoliosis, latex allergy, posterior cervical decompression, tracheostomy and/or gastrostomy tube.

RESULTS: Mortality (24%) continues to climb into young adulthood. Eighty-six percent of the cohort have cerebrospinal fluid diversion, with 95% having undergone at least one shunt revision. Thirty-two percent have undergone a tethered cord release, with 97% having an improvement or stabilization in their preoperative symptoms. Forty-nine percent have scoliosis, with 43% eventually requiring a spinal fusion. Sixteen patients (23%) have had at least one seizure. Eighty-five percent are attending or have graduated from high school and/or college. More than 80% of young adults have social bladder continence. Approximately 1/3 of patients are allergic to latex, with 6 patients having experienced a life-threatening reaction.

CONCLUSION: At least 75% of children born with a myelomeningocele can be expected to reach their early adult years. Late deterioration is common. One of the greatest challenges in medicine today is establishing a network of care for these adults with spina bifida. Copyright 2001 S. Karger AG, Basel

PMID: 11359098

Mental rotation ability of children with spina bifida: what influence does manual rotation training have

Wiedenbauer G, Jansen-Osmann P. Mental rotation ability of children with spina bifida: what influence does manual rotation training have? Developmental Neuropsychology. 2007;32(3):809-24.

We investigated the mental rotation ability of children with spina bifida, a malformation of the spinal cord due to a neural tube defect, and how it is influenced by a manual rotation training. In comparison to a healthy control group these children showed longer reaction times and a higher number of errors in a computer-based mental rotation test. Furthermore, a manual rotation training was applied. The spina bifida group benefited considerably from the manual rotation training. The training effect was not limited to stimuli learned in the training. While the children with spina bifida showed a lower speed of mental rotation than their healthy peers in the mental rotation pretest, the two groups did not differ in their mental rotation speed in the posttest.

PMID: 17956183

Sunday, October 21, 2007

The effect of C677T mutation of methylene tetrahydrofolate reductase gene and plasma folate level on hyperhomocysteinemia in patients with meningomyel

Lee BH, Cheong HI, Shin YS, Cho BK, Wang KC. The effect of C677T mutation of methylene tetrahydrofolate reductase gene and plasma folate level on hyperhomocysteinemia in patients with meningomyelocele. Child's Nervous System. 2000 Sep;16(9):559-63.

To evaluate the relationship between genotypes of methylene tetrahydrofolate reductase (MTHFR), and plasma folate and homocysteine (Hcy) levels in meningomyelocele, 21 Korean patients, 47 of their family members, and 43 healthy controls were recruited. The presence of C677T mutation in the MTHFR gene and plasma concentrations of folate/Hcy were investigated. The genotype frequency of C677T mutation was not higher in study groups (patients and family members). The plasma folate concentration showed no difference either between the study and the control groups or among MTHFR-genotypic groups. The plasma Hcy concentration in homozygotes in the study group was higher than that in the control group, and higher than that in heterozygotes when plasma folate levels were low (P=0.006). Although neither MTHFR genotype nor plasma folate/Hcy level plays a definite part on its own, they seem to have an additive effect on the occurrence of meningomyelocele. Our results support folate supplementation for the prevention of hyperhomocysteinemia and meningomyelocele.

PMID: 11048629

Homocysteine, folate, lipid profile and MTHFR genotype and disability in children with myelomeningocele

Rendeli C, Ausili E, Castorina M, Antuzzi D, Tabacco F, Caldarelli M. Homocysteine, folate, lipid profile and MTHFR genotype and disability in children with myelomeningocele. Child's Nervous System. 2006 Oct;22(10):1316-21. Epub 2006 Apr 7.

STUDY DESIGN: We performed a cross-sectional study in myelomeningocele children. OBJECTIVE: To investigate plasma total homocysteine, folate, lipid profile, 5,10- metylenetetrahydrofolate reductase genotype (MTHFR) and disability.

MATERIALS AND METHODS: Sixty patients aged between 2 and 14 years with myelomeningocele (18 ambulatory and 42 non-ambulatory) and 150 healthy children of same age, are investigated for lipid profile, homocysteine concentration and for the determination of MTHFR genotype.

RESULTS: Plasma homocysteine concentrations were significantly higher in myelomeningocele children than in the control group. In myelomeningocele female group, there were higher levels of total cholesterol and very-low-density lipoprotein cholesterol with respect to the control group. Myelomeningocele children walking with tutorial aid showed triglyceride levels significantly lower than those observed in myelomeningocele non-walking children.

CONCLUSION: Disability, insulin uptake, lipid, homocysteine, hormones plasma levels, and genetic factors such as allelic variants of MTHFR are possible for cardiovascular disease in myelomeningocele children. This study highlights the importance of a continuous surveillance of any changes in the lipid profile that should be corrected as soon as possible. Constant physical activity necessary to increase HDL levels should be planned in all susceptible children. Nonetheless, further investigations are necessary to identify new homocysteine susceptible genes for prevention of early atherosclerosis and consequent cardiovascular disease.

PMID: 16602021

Myelomeningocele: a review of the epidemiology, genetics, risk factors for conception, prenatal diagnosis, and prognosis for affected individuals

Shaer CM, Chescheir N, Schulkin J. Myelomeningocele: a review of the epidemiology, genetics, risk factors for conception, prenatal diagnosis, and prognosis for affected individuals. Obstetrical & Gynecological Survey. 2007 Jul;62(7):471-9. Review.

Although the use of folic acid before conception decreases the chance that a fetus will have an open neural tube defect, this condition still affects 0.5-1.0/1000 pregnancies in the United States. Results of a recent survey suggest that there are gaps in obstetrician-gynecologists' knowledge of risk factors for conception, strategies for prenatal diagnosis, and prognosis for affected individuals. To address these gaps this paper reviews the epidemiology, genetics, risk factors for conception, prenatal diagnosis, and prognosis for affected individuals, presents current information, and makes suggestions for expanding obstetrician-gynecologists' knowledge of myelomeningocele.

TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians.

LEARNING OBJECTIVES: After completion of this article, the reader should be able to state that despite a large amount of professional and public education on the use of folic acid in prevention of open neural tube defects (ONTDs) the incidence still affects 0.5-1.0/1000 pregnancies and recall that a recent survey conducted by the ACOG shows substantial misunderstanding and misinformation on major categories of neural tube birth defects.

PMID: 17572919

Friday, October 19, 2007

Severe constipation: an under-appreciated cause of VP shunt malfunction: a case-based update

Martinez-Lage JF, Martos-Tello JM, Ros-de-San Pedro J, Almagro MJ. Severe constipation: an under-appreciated cause of VP shunt malfunction: a case-based update. Child's Nervous System. 2007 Oct 10;

BACKGROUND: Increased intra-abdominal pressure has been reported to result in raised intracranial pressure in a variety of conditions such as obesity and pregnancy, and it also constitutes an infrequent cause of ventriculoperitoneal (VP) shunt malfunction. Patients with neurological deficits, as those with myelomeningocele or cerebral palsy, are prone to developing a neurogenic bowel and to suffer chronic constipation. Although previously recognized, VP shunt failure attributed to constipation has only recently been described. We briefly review the etiopathogenesis, diagnosis and management of severe constipation leading to VP shunt malfunction. Our aim is to draw the attention of pediatric neurosurgeons towards severe constipation as a possible cause of VP shunt failure thus avoiding unnecessary surgical valve revisions, to which children with hydrocephalus are often submitted to.

ILLUSTRATIVE CASES: We report two children that developed transient VP shunt failure because of intense constipation that caused exacerbation of previously shunted hydrocephalus. One of the patients constitutes the first description of this complication associated with an anteriorly placed anus and the other with intestinal paresis after ileostomy. Conservative treatment aimed at alleviating the increased intra-abdominal pressure resulted in complete resolution of the children's manifestations of VP shunt failure, without having to resort to surgical revision of the VP shunt.

PMID: 17926043

Friday, October 12, 2007

Tethered cord syndrome in childhood: diagnostic features and relationship to congenital anomalies

Michelson DJ, Ashwal S. Tethered cord syndrome in childhood: diagnostic features and relationship to congenital anomalies. Neurological Research. 2004 Oct;26(7):745-53. Review.

Tethered Cord Syndrome (TCS) is a stretch-induced functional disorder of the spinal cord that often develops and presents in childhood in association with spinal dysraphism. While the subtlety with which TCS can present makes it challenging to diagnose, awareness of the common neurological, musculoskeletal and urologic symptoms are of great value to the clinician, and can aid timely referral for neurosurgical evaluation. This article reviews these symptoms, as well as the clinical and radiological findings of the most common dysraphic conditions associated with TCS.

PMID: 15494116

What is the true tethered cord syndrome?

Yamada S, Won DJ. What is the true tethered cord syndrome? Child's Nervous System. 2007 Apr;23(4):371-5. Epub 2007 Jan 17.

INTRODUCTION: The tethered cord syndrome (TCS) is a stretch-induced functional disorder of the spinal cord with its caudal part anchored by an inelastic structure.

DISCUSSION: This article clarifies the reversible lesions that occur in the cord segments above any of the inelastic abnormalities. These lesions are found mostly in the lumbosacral cord, occasionally in the cervical cord and closely correlate with clinical findings. Imaging studies alone do not allow accurate diagnosis of the TCS. The authors emphasize the importance of adhering to the physiological terms
"tethered cord syndrome" and "tethered spinal cord" to avoid controversies derived from terms that are not based on the pathophysiology of TCS.

PMID: 17226037

Tethered cord due to spina bifida occulta presenting in adulthood: a tricenter review of 61 patients

Rajpal S, Tubbs RS, George T, Oakes WJ, Fuchs HE, Hadley MN, Iskandar BJ. Tethered cord due to spina bifida occulta presenting in adulthood: a tricenter review of 61 patients. Journal of Neurosurgery: Spine. 2007 Mar;6(3):210-5.

OBJECT: Children with spina bifida occulta require early surgery to prevent neurological deficits. The treatment of patients with a congenitally tethered cord who present in adulthood remains controversial.

METHODS: The authors studied the medical records of 61 adult patients who underwent surgical untethering for spina bifida occulta at three institutions between 1994 and 2003. Patients who had undergone prior myelomeningocele repair or tethered cord release surgery were excluded. The most common intraoperative findings were lipomyelomeningocele (41%) and a tight terminal filum (36%). The follow-up duration ranged from 10.8 to 149.5 months. Of the 34 patients with back pain, status improved in 65%, worsened in 3%, remained unchanged in 18%, and improved and later recurred in 15%. Lower-extremity pain improved in 16 patients (53%), remained unchanged in 23%, improved and then recurred in 17%, and worsened in 7%. Lower-extremity weakness improved in 47%, remained unchanged in 47%, and improved and then recurred in 5%. Finally, of the 17 patients with lower-extremity sensory changes, status improved in 35%, remained unchanged in 35%, and the information on five patients was unavailable. Surgical complications included three wound infections, one cerebrospinal fluid leak, and two pseudomeningoceles requiring surgical revision. One patient developed acute respiratory distress syndrome and sepsis postoperatively and died several days later.

CONCLUSIONS: Adult-age presentation of a congenital tethered cord is unusual. Despite a slight increase in postoperative neurological injury in adults, surgery has relatively low risk and offers good potential for neurological improvement or stabilization. As they do in children, the authors recommend early surgery in adults with this disorder. The decision to undertake surgery, however, should be modulated by other factors such as a patient's general medical condition and risk posed by anesthesia.

PMID: 17355019

Death in shunted hydrocephalic children: a follow-up study

Acakpo-Satchivi L, Shannon CN, Tubbs RS, Wellons JC 3rd, Blount JP, Iskandar BJ, Oakes WJ. Death in shunted hydrocephalic children: a follow-up study. Child's Nervous System. 2007 Jun 27; [Epub ahead of print]

INTRODUCTION: The authors previously conducted a retrospective study regarding deaths from CSF shunt failure to identify circumstances surrounding shunt malfunction-related deaths in children in the modern era.

MATERIALS AND METHODS: Using the same methodology, we conducted a follow-up study to determine whether recent policy and procedural changes instituted since the time of the first study had effected a change in the mortality rate of our shunted patient population.

RESULTS: Thirty-nine original patient records (of patients seen at Children's Hospital who died with the diagnosis of hydrocephalus between 1998 and 2004) were identified and reviewed for inclusion into the study. Only four (10.3%) were found to have died directly as a result of shunt malfunction.

CONCLUSIONS: Our rate of shunt malfunction death has decreased over time. It is reasonable to attribute part of this decline to continued improvements in diagnostic and therapeutic techniques and to the use of surveillance scans to identify asymptomatic patients with shunt failure. However, we believe the majority of this decline is due to two additional factors: (1) increased nursing staff and (2) effective patient/family education.

PMID: 17594102

Critical analysis of the Chiari malformation Type I found in children with lipomyelomeningocele

Tubbs RS, Bui CJ, Rice WC, Loukas M, Naftel RP, Holcombe MP, Oakes WJ. Critical analysis of the Chiari malformation Type I found in children with lipomyelomeningocele. Journal of Neurosurgery. 2007 Mar;106(3 Suppl):196-200.

OBJECT: Occasional comments are found in the literature regarding patients with lipomyelomeningocele and concomitant Chiari malformation Type I (CM-I). The object of this study was to explore the association between these two conditions.

METHODS: The authors performed a retrospective database analysis of lipomyelomeningocele cases to identify cases of concomitant CM-I. Analysis of posterior fossa volume (based on the Cavalieri principle) was performed in all identified cases in which appropriate neuroimages were available, and the results were compared with those obtained in age-matched controls. Seven (13%) of 54 patients with lipomyelomeningocele were found to also have CM-I. Two of these were symptomatic (cervicothoracic syrinx and occipital headaches) and required posterior fossa decompression. No correlation was found between the amount of hindbrain herniation and the level of the conus medullaris or the type of lipomyelome-ningocele (for example, caudal or transitional). Volumetric studies of the posterior fossa revealed normal age-matched volumes in all but one patient (who had asymptomatic CM-I).

CONCLUSIONS: The incidence of CM-I in patients with lipomyelomeningocele appears to be significantly greater than that of the general population and the association rate is too high for the finding to be a chance occurrence. Decreases in the volume of the posterior cranial fossa were not found in the majority of patients in this small cohort; therefore, the cause of the concomitant occurrence of lipomyelomeningocele and CM-I remains undetermined. Clinicians should consider obtaining imaging studies of the entire neuraxis in patients with lipomyelomeningoceles and should investigate other causes for syringes found in association with lipomyelomeningoceles.

PMID: 17465384

Predicting orthopedic involvement in patients with lipomyelomeningoceles

Tubbs RS, Winters RG, Naftel RP, Acharya VK, Conklin M, Shoja MM, Loukas M, Oakes WJ. Predicting orthopedic involvement in patients with lipomyelomeningoceles.
Child's Nervous System. 2007 Aug;23(8):835-8. Epub 2007 Mar 27.

INTRODUCTION: Lipomyelomeningoceles (LMM) occur in approximately 1 in every 4,000 live births in the United States. They are associated with a wide range of problems in affected patients, including skin abnormalities, sensory and motor deficits, pain, urinary bladder and anal sphincter dysfunction, and orthopedic deformities.

MATERIALS AND METHODS: In an effort to better understand the orthopedic complications associated with LMM, the present study examined the long-term orthopedic deformities in 50 patients after surgical correction of their LMM and observed for correlation between these deformities and the type and level of LMM.

RESULTS: Analysis of the collected data revealed a statistically significant relationship between of the type of LMM and the presence of orthopedic complications. However, no statistically significant relationship existed between the vertebral level of the LMM and the presence of orthopedic deformities. No correlation was identified between the level and type of LMM.

CONCLUSION: In this study, caudal LMM were much more likely than either dorsal or transitional types to have orthopedic complications. These data may prove useful to clinicians in predicting outcome and in counseling patients and their parents.

PMID: 17387484

Hydrocephalus in children born in 1999-2002: epidemiology, outcome and ophthalmological findings

Persson EK, Anderson S, Wiklund LM, Uvebrant P. Hydrocephalus in children born in 1999-2002: epidemiology, outcome and ophthalmological findings. Child's Nervous System. 2007 Oct;23(10):1111-8. Epub 2007 Apr 12.

OBJECTIVE: The purpose of this study was to monitor incidence and outcome in children with hydrocephalus.

MATERIALS AND METHODS: This is a population-based prospective study of all the children with hydrocephalus born in western Sweden in 1999-2002. Etiological and clinical information was collected from records, neuroimaging and ophthalmological examinations. Comparisons with 208 children born in 1989-1998 were made.

RESULTS: The incidence was 0.66 per 1,000 live births, 0.48 for infantile hydrocephalus and 0.18 for hydrocephalus associated with myelomeningocele. The corresponding rates for 1989-1998 were 0.82, 0.49 and 0.33. Ventriculo-peritoneal shunt treatment was used in 42 of the 54 children and endoscopic third ventriculostomy in 12. Revisions were performed in 33 (61%). Neurological impairments were present in 63%, and they were more common in children born preterm than in those born at term. The radiological extent of parenchymal lesions correlated significantly with outcome. Ophthalmological abnormalities were found in 80%, including visual impairment in one third.

CONCLUSION: The incidence of post-haemorrhagic hydrocephalus in children born extremely preterm increased; a group running a high risk of neurological sequelae. Ophthalmological abnormalities were frequent and need to be assessed in all children with hydrocephalus. The high rate of morbidity and complications necessitates the further development of preventive and treatment methods.

PMID: 17429657

Cervical meningomyelocele-an institutional experience

Kasliwal MK, Dwarakanath S, Mahapatra AK. Cervical meningomyelocele-an institutional experience. Child's Nervous System. 2007 Nov;23(11):1291-3. Epub 2007 Jul 13.

OBJECTIVE: Cervical myelomeningoceles (CMMC) are a less common but distinct subgroup of myelomeningoceles. Their embryology and clinical characteristics vary from the more common thoracolumbar variant. Only a few small series have been published addressing this lesion in the literature with the largest one of them addressing nine patients. The authors present one of the largest series of cervical myelomeningoceles, review their embryology, clinical features, and their management strategies.

METHODS: This study included all the children who were managed for cervical myelomeningocele between Jan 2001 to July 2006 at our center.

RESULTS: There were a total of ten children (five boys and five girls) operated on for cervical myelomeningoceles. The ages ranged between 2 months to 14 months. Neurological examination was normal in majority of the children with absence of gross orthopedic deformity in all the children. Three patients had associated hydrocephalus, two had Chiari malformation, and four of them had a syrinx. Surgical excision of the sac was performed for all.

CONCLUSION: Cystic dysraphisms of the cervical differ embryologically, clinically, and structurally from thoracolumbar meningomyelocele and have a more favorable outcome. A good pre operative evaluation is recommended to assess any associated anomalies and identify the internal structures. Surgery excision of these lesions with intradural exploration of the sac to release any potential adhesion bands as well as other associated anomalies is recommended.

PMID: 17628809

Sterile surgical technique for shunt placement reduces the shunt infection rate in children

Pirotte BJ, Lubansu A, Bruneau M, Loqa C, Van Cutsem N, Brotchi J. Sterile surgical technique for shunt placement reduces the shunt infection rate in children: preliminary analysis of a prospective protocol in 115 consecutive procedures. Child's Nervous System. 2007 Nov;23(11):1251-61. Epub 2007 Aug 18.

OBJECTIVE: The objective of this study was to evaluate whether the rigid application of a sterile protocol for shunt placement was applicable on a routine basis and allowed the reduction of shunt infections (SI) in children.

MATERIALS AND METHODS: Since 2001, a rigid sterile protocol for shunt placement in children using neither antibiotic-impregnated catheters nor laminar airflow was prospectively applied at Erasme Hospital, Brussels, Belgium. For assessing the protocol efficacy before continuation, we preliminarily analyzed the results of the first 100 operated children (43 females, 57 males, 49 aged <12 months; 115 consecutive shunt placement/revision procedures). All procedures were performed by the same senior surgeon, one assistant, one circulating nurse, one anesthesiologist. The sterile protocol was rigidly imposed to these four staff members: uniformed surgical technique; limited implant and skin edge manipulation; minimized human circulation in the room; scheduling surgery as first morning operation; avoiding postoperative cerebrospinal fluid (CSF) leak; double gloving; procedures of less than 30-min duration; systemic antibiotics prophylaxis. We analyzed separately: (1) children carrying an increased risk of SI (n = 38) due to preoperative external ventricular drainage, CSF leak, meningitis, glucocorticoids, chemotherapy; (2) children aged <12 months; (3) procedures for shunt revision.

RESULTS: Errors in protocol application were recorded in 71/115 procedures. They were mainly done by non-surgical staff, decreased with time and were medically justified in some young children. Surprisingly, no SI occurred (follow-up, 4 to 70 months). One child developed an appendicitis with peritonitis (Streptococcus faecalis) after 6 months. No SI was found. After peritonitis was cured, shunt reinsertion was uneventful.

CONCLUSION: These preliminary results suggest that a uniform and drastic sterile surgical technique for shunt placement: (1) can be rigidly applied on a routine basis; (2) can lower the early SI rate below 1%; (3) might have a stronger impact to reduce SI than using antibiotic-impregnated catheters and optimizing the operative environment such as using laminar airflow and reducing the non-surgical staff. This last issue will be evaluated further in the present ongoing protocol.

PMID: 17705062

Deliberate termination of life of newborns with spina bifida, a critical reappraisal

de Jong TH. Deliberate termination of life of newborns with spina bifida, a critical reappraisal. Child's Nervous System. 2007 Oct 10;

OBJECTS: Deliberate termination of life of newborns (involuntary euthanasia) with meningomyelocele (MMC) is practiced openly only in the Netherlands. 'Unbearable and hopeless suffering' is the single most cited criterion for this termination, together with the notion that 'there are no other proper medical means to alleviate this suffering'. In this paper, both (and other) statements are questioned, also by putting them in a broader perspective.

METHODS: First, a historical overview of the treatment of newborns with MMC is presented, concentrating on the question of selection for treatment. Second, a thorough analysis is made of the criteria used for life termination. Third, a case of a newborn with a very severe MMC is presented as a 'reference case'.

CONCLUSION: 'Unbearable and hopeless suffering' cannot be applied to newborns with MMC. They are not 'terminally ill' and do have 'prospects of a future'. In these end-of-life decisions, 'quality of life judgments' should not be applied. When such a newborn is not treated, modern palliative care always will suffice in eliminating possible discomfort. There is no reason whatsoever for active life-termination of these newborns.

PMID: 17929034

Sunday, October 7, 2007

CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population

Enaw JO, Zhu H, Yang W, Lu W, Shaw GM, Lammer EJ, Finnell RH. CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population. BMC Medicine. 2006 Dec 21;4:36.

BACKGROUND: Neural tube defects (NTDs) are among the most common of all human congenital defects. Over the last two decades, accumulating evidence has made it clear that periconceptional intake of folic acid can significantly reduce the risk of NTD affected pregnancies. This beneficial effect may be related to the ability of folates to donate methyl groups for critical physiological reactions. Choline is an essential nutrient and it is also a methyl donor critical for the maintenance of cell membrane integrity and methyl metabolism. Perturbations in choline metabolism in vitro have been shown to induce NTDs in mouse embryos.

METHODS: This study investigated whether single nucleotide polymorphisms (SNPs) in human choline kinase A (CHKA) gene and CTP:phosphocholine cytidylytransferase (PCYT1A) gene were risk factors for spina bifida. Fluorescence-based allelic discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388 (rs7928739) and hCV1562393, and PCYT1A SNP rs939883 and rs3772109. The study population consisted of 103 infants with spina bifida and 338 non-malformed control infants who were born in selected California counties in the period 1989-1991.

RESULTS: The CHKA SNP hCV1562388 genotypes with at least one C allele were associated with a reduced risk of spina bifida (odds ratio = 0.60, 95%CI = 0.38-0.94). The PCYT1A SNP rs939883 genotype AA was associated with a twofold increased risk of spina bifida (odds ratio = 1.89, 95% CI = 0.97-3.67). These gene-only effects were not substantially modified by analytic consideration to maternal periconceptional choline intake.

CONCLUSION: Our analyses showed genotype effects of CHKA and PCYT1A genes on spina bifida risk, but did not show evidence of gene-nutrient interactions. The underlying mechanisms are yet to be resolved.

PMID: 17184542

Maternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifida

Shaw GM, Lammer EJ, Zhu H, Baker MW, Neri E, Finnell RH. Maternal periconceptional vitamin use, genetic variation of infant reduced folate carrier (A80G), and risk of spina bifida.
American Journal of Medical Genetics. 2002 Feb 15;108(1):1-6. Erratum in: Am J Med Genet 2002 Dec 15;113(4):392.

Women who consume folic acid in early pregnancy reduced their risks for delivering offspring with neural tube defects (NTDs). The underlying process by which folic acid facilitated this risk reduction is unknown. Investigating genetic variation that influences cellular absorption, transport, and metabolism of folate will help fill this data gap. We focused our studies on a candidate gene that is involved in folate transport, the reduced folate carrier 1 (RFC1). Using data from a California population-based case control interview study (1989-1991 birth cohorts), we investigated whether spina bifida risk was influenced by an interaction between a polymorphism of infant RFC1 at nucleotide 80 (A80G) and maternal periconceptional use of vitamins containing folic acid. Allelic variants of RFC1 were determined by genotyping 133 live-born spina bifida case infants and 188 control infants. The percentages of case infants with the A80/A80, G80/G80, and G80/A80 genotypes were 27.2%, 28.0%, and 44.7%, respectively. The percentages of control infants were similar: 26.1%, 29.3%, and 44.7%. Odds ratios of 1.0 (95% confidence interval 0.5-2.0) for the G80/G80 genotype and 1.1 (0.6-2.0) for the G80/A80 genotype were observed relative to the A80/A80 genotype. Among mothers who did not use vitamins, spina bifida risk was 2.4 (0.8-6.9) for infants with genotype G80/G80 compared to those with A80/A80 genotype. Among mothers who did use vitamins, the risk was 0.5 (0.1-3.1) for infants with the G80/G80 genotype. Although this study did not find an increased spina bifida risk for infants who were heterozygous or homozygous for RFC1 A80G, it did reveal modest evidence for a gene-nutrient interaction between infant homozygosity for the RFC1 G80/G80 genotype and maternal periconceptional intake of vitamins containing folic acid on the risk of spina bifida. Copyright 2002 Wiley-Liss, Inc.

PMID: 11857541

Saturday, October 6, 2007

The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk of spina bifida

Jensen LE, Hoess K, Whitehead AS, Mitchell LE. The NAT1 C1095A polymorphism, maternal multivitamin use and smoking, and the risk of spina bifida.
Birth Defects Research Part A: Clinical and Molecular Teratology. 2005 Jul;73(7):512-6.

BACKGROUND: The risk of having a child with a neural tube defect (NTD) can be reduced by maternal, periconceptional supplementation with folic acid, but the underlying folate-dependent protective mechanism remains unclear. N-acetyltransferase 1 is involved in acetylation of aromatic and heterocyclic amines and the catabolism of folates. Hence, functional polymorphisms in NAT1, the gene encoding N-acetyltransferase 1, are plausible risk factors for NTDs. Such variants could exert an influence on the risk of NTDs via their role in acetylation or folate catabolism and could act through the maternal or the embryonic genotype.

METHODS: NAT1 C1095A genotypes and information on maternal, periconceptional multivitamin use and smoking were obtained as part of a family-based study of spina bifida. Associations between spina bifida and the embryonic and maternal NAT1 C1095A genotypes, and potential NAT1 C1095A genotype-exposure interactions were evaluated using log-linear modeling.

RESULTS: The analyses provided no evidence that the embryonic or maternal NAT1 C1095 genotypes influence the risk of spina bifida independently, or through interactions with maternal use of multivitamins. There was evidence that the embryonic, and possibly the maternal, NAT1 C1095A genotype influence the risk of spina bifida via interactions with maternal smoking status.

CONCLUSIONS: The genotype for the NAT1 C1095A polymorphism does not appear to be an independent risk factor for spina bifida. However, the results of these analyses provide preliminary evidence that this polymorphism may be associated with the risk of spina bifida in the offspring of women who smoke during early pregnancy. (c) 2005 Wiley-Liss, Inc.

PMID: 15959877

Dependence and perceived difficulty in activities of daily living in adults with cerebral palsy and spina bifida

Andren E, Grimby G. Dependence and perceived difficulty in activities of daily living in adults with cerebral palsy and spina bifida. Disability & Rehabilitation. 2000 May 10;22(7):299-307.

PURPOSE: The purpose of this study was to identify differences between two groups of subjects: one with cerebral palsy, the other with spina bifida in their dependence and their perceived difficulty in performing daily activities according to the Functional Independence Measure (FIM) and the Instrumental Activity Measure (IAM), and to compare these findings with the reported use of assistance.

METHOD: Community-living persons. 53 with cerebral palsy and 20 with spina bifida, aged 20 to 39 years, participated in semistructured interviews in their homes, where rating was performed using items from FIM and IAM.

RESULTS: Differences were found for the reported use of assistance and the dependence rated according to FIM and IAM. Significant differences for dependence were found between the CP and SB subjects concerning Eating, Bladder and Bowel items and for perceived difficulty concerning toileting, bladder and bowel. There was close overall agreement between dependence and perceived difficulty, except for the item walk/wheelchair.

CONCLUSIONS: Subjects in both groups needed help in basic and instrumental ADL. The ability of spina bifida subjects was more influenced in toileting, bladder, bowel than the cerebral palsy subjects and tended also to be so in mobility instrumental tasks. FIM and IAM do not cover all aspects of significance in community-living adults. Further items have to be developed, covering personal care and occupational as well as leisure domains.

PMID: 10877483

The transition study: a look at youth and adults with cerebral palsy, spina bifida and acquired brain injury

Young N, McCormick A, Mills W, Barden W, Boydell K, Law M, Wedge J, Fehlings D, Mukherjee S, Rumney P, Williams JI. The transition study: a look at youth and adults with cerebral palsy, spina bifida and acquired brain injury.
Physical and Occupational Therapy in Pediatrics. 2006;26(4):25-45.

A group of 100 adults and 190 youth who have cerebral palsy (CP), spina bifida (SB), and acquired brain injuries from childhood (ABIc) participated in a multi-method study focused on the transition to adult health care. The results show that 95% of youth and 61% of adults were living with their parents; 23% of the youth and 55% of adults were employed; and 60% of youth and 42% of adults reported "excellent" or "very good" health. The lowest health scores were reported by adults with SB. These findings provide a starting point for examining health issues specific to youth and young adults with CP, SB, and ABIc.

PMID: 17135068

Minimally invasive approach for treatment of urinary and fecal incontinence in selected patients with spina bifida

Lorenzo AJ, Chait PG, Wallis MC, Raikhlin A, Farhat WA. Minimally invasive approach for treatment of urinary and fecal incontinence in selected patients with spina bifida. Urology. 2007 Sep;70(3):568-71.

OBJECTIVES: At our institution, the use of cecostomy tubes has provided a successful method for managing severe constipation in patients with spina bifida, with good patient and caretaker satisfaction and minimal morbidity. We have developed a modified technique to allow placement of the cecostomy tube under direct vision during laparoscopic appendicovesicostomy. We present our initial experience and technique.

METHODS: Patients with a normal bladder capacity and compliance who were scheduled for creation of an appendicovesicostomy and who also had refractory constipation were offered concurrent cecostomy tube placement. At the laparoscopic procedure, we performed percutaneous placement of the cecostomy tube through the abdominal wall under direct visualization. Subsequently, dissection of the appendix with its mesentery was performed. The detrusor muscle was dissected and a trough for the appendix created. Laparoscopic anastomosis of the appendix to the bladder mucosa and approximation of the detrusor over the appendix created a nonrefluxing channel. RESULTS: Three patients have undergone concurrent cecostomy tube placement at appendicovesicostomy. No complications have been encountered thus far. On follow-up, the cecostomy tube scar has been well concealed and appears no different from the ones placed under radiologic guidance. The patients have been using the catheterizable channel to access the bladder and dry performing intermittent catheterization without difficulties.

CONCLUSIONS: In patients with a neurogenic bladder who do not qualify for major bladder reconstructive procedures, such as augmentation cystoplasty or bladder neck repair, social continence and independence can be achieved with minimally invasive surgery. Concomitant laparoscopic appendicovesicostomy and cecostomy tube placement may be a suitable surgical option.

PMID: 17905118

The transition from child to adult in neurosurgery

Vinchon M, Dhellemmes P. The transition from child to adult in neurosurgery.
Advances and Technical Standards in Neurosurgery. 2007;32:3-24.

The transition from child to adult is a growing concern in neurosurgery. Data documenting long-term follow-up are necessary to define this population's healthcare needs. In order to evaluate the problems posed by the child-to-adult transition in neurosurgery, we have studied the neurological, functional and social outcome of patients treated in our department for tumor of the central nervous system, hydrocephalus or myelomeningocele, and followed beyond the age of eighteen years. A large number of patients suffered from chronic ailments, either sequelae of their initial disease, or delayed complications of their initial treatment, with significant morbidity. The mortality during adulthood was 4.6% in the tumor group, 1.1% in the hydrocephalus group, and zero in the spina bifida group. The proportion of patients employed in normal jobs was 35.6, 18.7 and 11.5% for tumors, hydrocephalus and myelomeningocele respectively. IQ score and performance at school generally overestimated the capacity for social integration. Based on these data and on the available literature, we tried to identify the problems and devise solutions for the management of the transition from child-to-adulthood transition. Many problems present during childhood persist to adulthood, some of which are made more acute because of a more competitive environment, the lack of structures and inadequate medical follow-up. The transition from child to adult must be managed jointly by pediatric and adult neurosurgeons. More clinical research is required in order to precisely evaluate the problems posed by adult patients treated during childhood for the different neurosurgical diseases. Based on these data, a concerted trans-disciplinary approach is necessary, tailored to the specific needs of patients suffering from different diseases.

PMID: 17907472

Monday, October 1, 2007

A model of comprehension in spina bifida meningomyelocele: meaning activation, integration, and revision.

Barnes MA, Huber J, Johnston AM, Dennis M. A model of comprehension in spina bifida meningomyelocele: meaning activation, integration, and revision.
Journal of the International Neuropsychological Society. 2007 Sep;13(5):854-64.

Spina bifida meningomyelocele (SBM) is a neurodevelopmental disorder associated with adequate development of word reading and single word comprehension, but deficient text and discourse comprehension. Studies of comprehension in children with SBM are reviewed in relation to a comprehension model in which meanings are either activated from the surface code or constructed through resource-intensive integration and revision processes to form representations of the text base and models of the situation described by the text. Two new studies probed the construction of situation models in SBM. Experiment 1 tested the ability to build spatial and affective situation models from single sentences in 86 children with SBM (8 to 18 years of age) and 37 control children (8 to 16 years of age). Experiment 2 tested the ability to integrate across sentences to build spatial situation models in 15 children with SBM and 15 age-matched controls. Compared to age peers, children with SBM did not construct situation models that required integration of information across sentences, even though they could construct such models from single sentences. The data bear on the distinctive SBM neurocognitive profile, and more generally, on the significance of integration processes for the constructive aspects of language comprehension.

PMID: 17697417

Non-traditional management of the neurogenic bladder: tissue engineering and neuromodulation.

Lewis JM, Cheng EY. Non-traditional management of the neurogenic bladder: tissue engineering and neuromodulation. Scientific World Journal. 2007 Aug 17;7:1230-41.

Patients with spina bifida and a neurogenic bladder have traditionally been managed with clean intermittent catheterization and pharmacotherapy in order to treat abnormal bladder wall dynamics, protect the upper urinary tract from damage, and achieve urinary continence. However, some patients will fail this therapy and require surgical reconstruction in the form of bladder augmentation surgery using reconfigured intestine or stomach to increase the bladder capacity while reducing the internal storage pressure. Despite functional success of bladder augmentation in achieving a low pressure reservoir, there are several associated complications of this operation and patients do not have the ability to volitionally void. For these reasons, alternative treatments have been sought. Two exciting alternative approaches that are currently being investigated are tissue engineering and neuromodulation. Tissue engineering aims to create new bladder tissue for replacement purposes with both "seeded" and "unseeded" technology. Advances in the fields of nanotechnology and stem cell biology have further enhanced these tissue engineering technologies. Neuromodulation therapies directly address the root of the problem in patients with spina bifida and a neurogenic bladder, namely the abnormal relationship between the nerves and the bladder wall. These therapies include transurethral bladder electrostimulation, sacral neuromodulation, and neurosurgical techniques such as selective sacral rhizotomy and artificial somatic-autonomic reflex pathway construction. This review will discuss both tissue engineering techniques and neuromodulation therapies in more detail including rationale, experimental data, current status of clinical application, and future direction.

PMID: 17704856

Conservative treatment of Charcot artroparthy in a series of spina bifida patients: the experience of one center and review of the literature.

Yalcin S, Kocaoglu B, Berker N, Erol B. Conservative treatment of Charcot artroparthy in a series of spina bifida patients: the experience of one center and review of the literature. Journal of Pediatric Orthopedic B. 2007 Sep;16(5):373-9.

The present study was performed to evaluate the use of patellar tendon-bearing ankle foot orthesis for the treatment of Charcot arthropathy in a series of patients with spina bifida. A cohort of 350 spina bifida patients, ages ranging between 12 months and 22 years were evaluated in our clinic between June 1993 and March 2004. Charcot arthropathy was seen in five of these children. Treatment was initiated with nonsteroidal anti-inflammatory drugs, oral bisphosphonates and immobilization. No change was observed in the patients' symptoms after a month of treatment. At this time, a patellar tendon-bearing ankle foot orthesis was prescribed and used for a period of 6 to 24 months. All patients improved within 2 months. At the end of 2 years of follow-up, three patients are still using the brace without any complaints. One patient still has symptoms, although she is wearing her brace, but she has had significant improvement compared with the initiation of therapy. Non-weight-bearing, immobilization and surgery are the known treatment choices in Charcot arthropathy. Little experience exists about this entity and its treatment. Our experience reveals that the patellar tendon-bearing ankle foot orthesis leads to significant improvement in children with Charcot arthropathy without surgery and immobilization.

PMID: 17762679

Charcot arthropathy in spina bifida.

Nagarkatti DG, Banta JV, Thomson JD. Charcot arthropathy in spina bifida. Journal of Pediatric Orthopedics. 2000 Jan-Feb;20(1):82-7.

This multicenter study was undertaken to identify the prevalence of Charcot arthropathy in the spina bifida population; to evaluate the relationship of neurosegmental level, ambulatory level, and distribution of joint involvement; and to assess treatment results and make treatment recommendations. Sixteen patients were identified with Charcot arthropathy based on clinical and radiographic criteria ranging in age from 9 to 42 years. There were 15 ankles, seven knees, and four hips identified with Charcot arthropathy. Six patients underwent surgery and modification of orthoses, eight had a modification of orthoses only, one had no modification, and one was lost to follow-up. Mean follow-up was 4 years and 9 months (with four good, 17 fair, and five poor results). The best results were seen in 13 compliant patients with a brace modification, whereas poor results were seen in three patients with poor brace compliance. Based on our study, we have noted the prevalence of Charcot arthropathy in spina bifida to be one in 100 cases.

PMID: 10641695

Factors affecting renal scar development in children with spina bifida

Ozel SK, Dokumcu Z, Akyildiz C, Avanoglu A, Ulman I. Factors affecting renal scar development in children with spina bifida. Urologia Internationalis. 2007;79(2):133-6.

BACKGROUND/AIMS: Prevention of renal scarring is the main therapeutic goal in children with spina bifida. We aimed to determine factors affecting renal scar development in these patients.

MATERIALS AND METHODS: Records of 312 children admitted between 1994 and 2005 with spina bifida were reviewed. Age on admission, gender, presence of previous febrile urinary tract infections (UTIs), vesicoureteral reflux (VUR), and initial urodynamic findings were noted. Patients were grouped regarding presence/absence of renal scars on DMSA scans. Chi2 and Student's t tests were used for statistical evaluation.

RESULTS: Seventy-two patients had renal scars on admission. Mean age was 4.62 +/- 4.59 years for patients without renal scars and 6.35 +/- 4.9 years for patients with scars. Male/female ratio was 1:1 in the scarless group and 1:2 in the group with scars. Previous febrile UTI was present in 11 of 240 scarless patients in contrast to 7 out of 72 patients in the scar group (p > 0.05). VUR was present in only 16.3% of cases without scars, whereas 36.1% of patients in the scar group had VUR. Detrusor overactivity and detrusor sphincter dyssynergia were observed in 67.1% of scarred patients, whereas this figure was 42.4% in the scarless group. The comparison of age on admission, gender, detrusor overactivity, and detrusor sphincter dyssynergia revealed significant differences between patients with and without renal scars.

CONCLUSIONS: Late referral, female gender, overactive detrusor, and detrusor sphincter dyssynergia have detrimental effects on renal parenchymal function in spina bifida patients. Patient selection for aggressive treatment using these features may prevent renal parenchymal deterioration. 2007 S. Karger AG, Basel

PMID: 17851282

Age-related Differences in Executive Function Among Children with Spina Bifida/Hydrocephalus Based on Parent Behavior Ratings

Tarazi RA, Zabel TA, Mahone EM. Age-related Differences in Executive Function Among Children with Spina Bifida/Hydrocephalus Based on Parent Behavior Ratings.
Clinical Neuropsychology. 2007 Aug 18;:1-18

Previous research has suggested that adolescents with myelomeningocele and shunted hydrocephalus (MMH) have difficulties with aspects of executive functioning and, in turn, with functional independence. There is little research, however, examining patterns of executive functioning across adolescence in this population. The goal of this cross-sectional study was to examine parent ratings of executive function in children with MMH and in typically developing peers across late childhood and adolescence. Parents of 36 individuals with MMH and 35 typically developing peers, ages 10 to 18 years, completed the Behavior Rating Inventory of Executive Function (BRIEF). The BRIEF is organized into eight scales and two primary indices - Metacognition (MCI) and Behavioral Regulation (BRI). As a whole, the children with MMH had significantly higher BRIEF T-scores, as well as a higher prevalence of clinically significant T-scores across subscales, particularly those representing cognitive control. Effects of group, age, and age-by-group interactions on the mean raw scores of the MCI and BRI were examined using regression analyses. There were significant group effects (p < .05) for both the BRI and MCI, with the controls having significantly lower mean ratings than the MMH group. There was also a significant contribution of age-by-group interaction on the BRI (p < .05). Although mean raw scores on the BRI for the MMH group remained stable across ages, mean raw scores in the control group decreased as age increased. Thus, healthy children have age-related improvements in executive control behaviors across adolescence, particularly behavioral control, while children with MMH demonstrate no age-related improvements in parent reported executive behaviors across adolescence. Therefore, children with MMH may continue to require targeted interventions and modifications to address executive dysfunction into young adulthood in order to promote functional independence.

PMID: 17853154

Identification of minimal enhancer elements sufficient for Pax3 expression in neural crest and implication of Tead2 as a regulator of Pax3

Milewski RC, Chi NC, Li J, Brown C, Lu MM, Epstein JA. Identification of minimal enhancer elements sufficient for Pax3 expression in neural crest and implication of Tead2 as a regulator of Pax3. Development. 2004 Feb;131(4):829-37. Epub 2004 Jan 21.

Pax3 is a transcription factor that is required by pre-migratory neural crest cells, which give rise to the peripheral nervous system, melanocytes, some vascular smooth muscle, and numerous other derivatives [corrected]. Both mice and humans with Pax3 deficiency exhibit neural crest-related developmental defects [corrected]. Pax3 is also expressed in the dorsal neural tube, and by myogenic progenitors in the presomitic mesoderm and the hypaxial somites. Molecular pathways that regulate Pax3 expression in the roof plate probably represent early upstream signals in neural crest induction. We have identified an enhancer region in the Pax3 genomic locus that is sufficient to recapitulate expression in neural crest precursors in transgenic mice. We show that Tead2, a member of the Tead box family of transcription factors, binds to a neural crest enhancer and activates Pax3 expression. Tead2, and its co-activator YAP65, are co-expressed with Pax3 in the dorsal neural tube, and mutation of the Tead2 binding site in the context of Pax3 transgenic constructs abolishes neural expression. In addition, a Tead2-Engrailed fusion protein is able to repress retinoic acid-induced Pax3 expression in P19 cells and in vivo. These results suggest that Tead2 is an endogenous activator of Pax3 in neural crest.

PMID: 14736747

Transcription factor TEAD2 is involved in neural tube closure.

Kaneko KJ, Kohn MJ, Liu C, Depamphilis ML. Transcription factor TEAD2 is involved in neural tube closure. Genesis. 2007 Sep;45(9):577-87.

TEAD2, one of the first transcription factors expressed at the beginning of mammalian development, appears to be required during neural development. For example, Tead2 expression is greatest in the dorsal neural crest where it appears to regulate expression of Pax3, a gene essential for brain development. Consistent with this hypothesis, we found that inactivation of the Tead2 gene in mice significantly increased the risk of exencephaly (a defect in neural tube closure). However, none of the embryos exhibited spina bifida, the major phenotype of Pax3 nullizygous embryos, and expression of Pax3 in E11.5 Tead2 nullizygous embryos was normal. Thus, Tead2 plays a role in neural tube closure that is independent of its putative role in Pax3 regulation. In addition, the risk of exencephaly was greatest with Tead2 nullizygous females, and could be suppressed either by folic acid or pifithrin-alpha. These results reveal a maternal genetic contribution to neural tube closure, and suggest that Tead2-deficient mice provide a model for anencephaly, a common human birth defect that can be prevented by folic acid. genesis 45:577-587, 2007. Published 2007 Wiley-Liss, Inc.

PMID: 17868131

Incidence, prevalence, and characteristics of fractures in children, adolescents, and adults with spina bifida

Dosa NP, Eckrich M, Katz DA, Turk M, Liptak GS. Incidence, prevalence, and characteristics of fractures in children, adolescents, and adults with spina bifida. Journal of Spinal Cord Medicine. 2007;30 Suppl 1:S5-9.

OBJECTIVE: To determine the age-specific incidence, prevalence, and characteristics of fractures in persons with spina bifida. DESIGN: Year-long historical cross-sectional study.

SUBJECTS: Two hundred twenty-one consecutive patients aged 2-58 years evaluated in 2003 at a regional referral center. Twenty percent (n=44) were children age 2-10 years; 30% (n=68) were adolescents age 11-18 years; and 50% (n=109) were adults age 19-58 years. Fifty-five percent (n=121) were female; 64% (n=141) had shunted hydrocephalus. Fifty-eight percent (n=129) were community ambulators. Defect levels included 14% (n=31) thoracic; 37% (n=81) mid-lumbar; 35% (n=79) low-lumbar; and 14% (n = 30) sacral.

METHODS: Chart review of 221 consecutive children, adolescents, and adults enrolled in a spina bifida program in Syracuse, New York, was used to determine incidence and prevalence rates. Chi-square was used for subgroup analyses, and linear regression was used to examine independent association of motor level, functional independence (Functional Independence Measures score), body mass index (BMI), shunted hydrocephalus, epilepsy, and/or other congenital anomalies with fractures, controlling for insurance status, race/ethnicity, age, and sex.

RESULTS: Annual incidence of fractures among children, adolescents, and adults was 23/1000; 29/1000; and 18/1000, respectively. Overall prevalence was 200/1000. One in 4 patients with fractures reported multiple fractures. Median age at first fracture was 11 years. Most fractures involved the femur or tibia. Comparisons between adult- and childhood-onset fractures were not significant for difference in sex, BMI, defect level, functional independence, shunted hydrocephalus, epilepsy, or other congenital anomalies. In regression models only defect level RR = 1.646 (P = 0.019; 95% CI 1.085-2.498) and age RR = 1.033 (P= 0.036; 95% CI 1.002-1.065) were independently associated with fractures.

CONCLUSIONS: Fractures in persons with spina bifida are most common during early adolescence. Environmental modifications may be more effective than pharmacological treatment in reducing the prevalence of fractures in this population.

PMID: 17874679

Renal cortical deterioration in children with spinal dysraphism: analysis of risk factors

DeLair SM, Eandi J, White MJ, Nguyen T, Stone AR, Kurzrock EA. Renal cortical deterioration in children with spinal dysraphism: analysis of risk factors. Journal of Spinal Cord Medicine. 2007;30 Suppl 1:S30-4.

BACKGROUND/OBJECTIVE: Because hydronephrosis and reflux are reversible, we believe cortical loss represents true renal deterioration in children with spinal dysraphism. Our goal was to better define risk factors for cortical loss.

METHODS: After institutional review board approval, we reviewed the medical records of 272 children with spinal dysraphism. The following factors were evaluated: age, sex, renal and bladder imaging, urodynamic parameters, medications, catheterization program, continence, infections, and surgical history. Renal cortical loss was defined by scarring or a differential function greater than 15% using a nuclear scan. Univariate and multivariate logistic regression models were fitted to test the associations of specific variables with cortical loss.

RESULTS: Renal cortical loss was found in 41% of children with high-grade reflux vs. 2% of children without reflux. Univariate analysis showed only high-grade reflux and female sex to be independent risk factors. Controlling for age and sex, reflux and initiation of catheterization after 1 year of age are significant risk factors. High bladder pressure and hydronephrosis in the absence of reflux were not associated with cortical loss. Multivariate analysis showed that girls with reflux have a 55-fold increased risk of cortical loss.

CONCLUSION: By limiting the definition of renal deterioration to cortical loss, we identified relevant risk factors: reflux, female sex, and delayed initiation of clean intermittent catheterization. We have also discounted other suspected risk factors: hydronephrosis and elevated bladder pressure. Rather than continuing our focus on hydronephrosis and urodynamics, we believe more research and management debate should be afforded to females with reflux.

PMID: 17874684

Aerobic fitness and upper extremity strength in patients aged 11 to 21 years with spinal cord dysfunction as compared to ideal weight and overweight c

Widman LM, Abresch RT, Styne DM, McDonald CM. Aerobic fitness and upper extremity strength in patients aged 11 to 21 years with spinal cord dysfunction as compared to ideal weight and overweight controls. Journal of Spinal Cord Medicine. 2007;30 Suppl 1:S88-96.

OBJECTIVE: To determine whether the aerobic fitness, upper extremity strength, and body composition in groups of adolescents with mobility impairment due to thoracic and upper lumbar spinal cord injury (SCI) or spina bifida (SB) are significantly different from those in groups of adolescents without mobility impairment who are of normal weight (CTRL) or overweight (OW).

SUBJECTS: One hundred fifteen total subjects were evaluated including 59 female (19 SB, 9 SCI, 17 OW, and 14 CTRL) and 56 male (18 SB, 10 SCI, 8 OW, and 20 CTRL) participants aged 11 to 21 years.

METHODS: Aerobic fitness was assessed using a ramp protocol with a magnetically braked arm ergometer. Heart rate and oxygen uptake (VO2) were recorded. Peak isokinetic upper arm and shoulder strength values were determined with a dynamometer. Body composition was estimated using dual energy x-ray absorptiometry (DEXA). Male and female subjects were categorized as overweight if their percent body fat by DEXA exceeded 25% and 30%, respectively. Results were analyzed with an ANOVA using the Bonferroni correction. Significance was accepted at P < 0.05.

RESULTS: The percent body fat of both the male and female SB and SCI subjects was significantly higher than CTRL but was not different than OW. In general, the shoulder extension and flexion strength in both the SB and SCI males and females was significantly lower than that of the CTRL and OW. The SCI and SB subjects had significantly reduced aerobic capacity (VO2/kg) compared to the CTRL subjects but were not different than the OW subjects. During the maximal exercise test, the SB and SCI subjects reached exhaustion at significantly lower workloads than the CTRL and OW subjects.

CONCLUSIONS: Patients age 11 to 21 years with SB and SCI had reduced aerobic capacity that was associated with being overweight and having reduced upper extremity strength. These data suggest that interventions to increase strength and fitness and to manage weight should be recommended in this population.

PMID: 17874693

Body composition and resting energy expenditure in patients aged 11 to 21 years with spinal cord dysfunction compared to controls: comparisons and rel

Liusuwan RA, Widman LM, Abresch RT, Styne DM, McDonald CM. Body composition and resting energy expenditure in patients aged 11 to 21 years with spinal cord dysfunction compared to controls: comparisons and relationships among the groups.
Journal of Spinal Cord Medicine. 2007;30 Suppl 1:S105-11.

OBJECTIVES: To compare body composition in patients aged 11 to 21 years with spinal dysfunction due to spinal cord injury (SCI) and spina bifida (SB) vs. able-bodied control (CTRL) and able-bodied overweight (OW) groups and to examine the relationships between resting energy expenditure (REE) and total lean mass (TLM) in the SCI, SB, CTRL, and OW groups.

METHODS: Two hundred fifteen subjects, including 85 CTRL, 31 OW, 33 SCI, and 66 SB, were evaluated. Body composition was estimated by dual energy x-ray absorptiometry (DXA). Measurements included height, weight, total lean mass (TLM), fat tissue mass (FTM), body mass index (BMI), BMI percentile (BMI%tile), and % fat. Resting energy measurements were obtained in fasting subjects with an open-circuit indirect calorimeter.

RESULTS: There were gender differences in height, weight, BMI, TLM, fat mass, % fat, and REE. The REE in the SCI and SB groups was significantly different from that in the CTRL and OW groups, but no significant difference was found between the SCI and SB groups. The SB group had significantly higher REE/TLM ratios than did the other groups. The % fat was significantly higher in the SB and OW groups as compared to the CTRL and SCI groups. TLM was significantly higher in CTRL and OW groups as compared to SCI and SB groups, with the lowest TLM found in the SB group.

CONCLUSION: Patients aged 11 to 21 years with SB or SCI have significant lean tissue mass deficits by DXA as compared to able-bodied CTRL and OW groups, with the greatest deficits in total lean mass measured in SB. The absolute REE values were significantly reduced in both SCI and SB groups in association with their lean tissue deficits. Interestingly, REE/TLM ratios were remarkably constant in the CTRL, OW, and SCI groups but significantly elevated in the SB group. One would expect an even greater degree of adiposity in the SB group if their REE/TLM ratios were not elevated relative to those without congenital paralysis.

PMID: 17874695

Impact of spinal cord dysfunction and obesity on the health-related quality of life of children and adolescents.

Abresch RT, McDonald DA, Widman LM, McGinnis K, Hickey KJ. Impact of spinal cord dysfunction and obesity on the health-related quality of life of children and adolescents. Journal of Spinal Cord Medicine. 2007;30 Suppl 1:S112-8.

OBJECTIVES: The objectives of this study were: (1) to compare the health-related quality of life (HRQOL) of children and adolescents with mobility impairments due to spinal cord injury (SCI) and spina bifida (SB) to the HRQOL of children and adolescent controls without mobility impairments (CTRL); and (2) to examine the impact of of obesity on the HRQOL of these subjects.

METHODS: The Pediatric Quality of Life Inventory (PedsQL) was administered to 42 SB, 71 SCI and 60 able-bodied subjects who were 8-20 years of age. Subjects were categorized as obese if their BMI exceeded the 95th percentile for age. Twenty-one CTRL, 26 SB and 26 SCI subjects were obese.

RESULTS: The SCI and SB subjects had significantly lower subscores than the control subjects on the physical (p < 0.001), emotional (p < .01), social (p < .001), and school (p < .001) domains of the PedsQL. The obese (CTRL) group had lower subscores on the physical (p < 0.001), social (p < 0.001), and psychosocial (p < 0.001) domains of the PedsQL as compared to the non-obese CTRL group, while there were no significant differences in subscores from the emotional and school domains. In contrast to the subjects without mobility impairment, there were no significant differences between the sub-scores of the obese and non-obese subjects with spinal cord dysfunction secondary to SCI or SB. The mean total PedsQL score of the non-obese control group (87.7 +/- 2.1) was significantly higher than the obese control group (75.2 +/- 3.4, p < 0.02), which in turn was significantly higher than the SCI group (63.7 +/- 2.2, p < 0.02), and the SB group (63.0 +/- 2.2, p < 0.02).

CONCLUSION: Patients with SCI and SB have significantly lower HRQOL than children and adolescents without mobility impairments. Whereas obesity significantly reduces the quality of life scores of adolescents without mobility impairments, it has no significant incremental effect on subjects with SCI or SB.


Metabolic syndrome in adolescents with spinal cord dysfunction

Nelson MD, Widman LM, Abresch RT, Stanhope K, Havel PJ, Styne DM, McDonald CM.
Metabolic syndrome in adolescents with spinal cord dysfunction.
Journal of Spinal Cord Medicine. 2007;30 Suppl 1:S127-39.

OBJECTIVE: The purpose of this study was to determine the prevalence of components of the metabolic syndrome in adolescents with spinal cord injury (SCI) and spina bifida (SB), and their associations with obesity in subjects with and without SCI and SB.

METHODS: Fifty-four subjects (20 SCI and 34 SB) age 11 to 20 years with mobility impairments from lower extremity paraparesis were recruited from a hospital-based clinic. Sixty able-bodied subjects who were oversampled for obesity served as controls (CTRL). Subjects were categorized as obese if their percent trunk fat measured by dual x-ray absorptiometry (DXA) was > 30.0% for males and > 35.0% for females. Ten SCI, 24 SB, and 19 CTRL subjects were classified as obese. Fasting serum samples were collected to determine serum glucose, insulin, and lipid concentrations. Metabolic syndrome was defined as having > or =3 of the following components: (a) obesity; (b) high-density lipoprotein (HDL) <45 mg/dL for males; <50 mg/dL for females; (c) triglycerides 2100 mg/dL; (d) systolic or diastolic blood pressure > or =95th percentile for age/ height/gender, and (e) insulin resistance determined by either fasting serum glucose 100-125 mg/dL; fasting insulin > or =20 microU /mL; or homeostasis model assessment of insulin resistance > or = 4.0.

RESULTS: Metabolic syndrome was identified in 32.4% of the SB group and 55% of the SCI group. Metabolic syndrome occurred at a significantly higher frequency in obese subjects (SB = 45.8%, SCI = 100%, CTRL = 63.2%) than nonobese subjects (SB = 0%, SCI = 10%, CTRL = 2.4%).

CONCLUSIONS: The prevalence of metabolic syndrome in adolescents with SB/SCI is quite high, particularly in obese individuals. These findings have important implications due to the known risks of cardiovascular diseases and diabetes mellitus associated with metabolic syndrome in adults, particularly those with spinal cord dysfunction.

PMID: 17874698

Tethering tracts in spina bifida occulta: revisiting an established nomenclature

Rajpal S, Salamat MS, Tubbs RS, Kelly DR, Oakes WJ, Iskandar BJ.
Tethering tracts in spina bifida occulta: revisiting an established nomenclature.
Journal of Neurosurgery. Spine. 2007 Sep;7(3):315-22.

OBJECT: The goal of the present study goal was to systematically confirm the previously recognized nomenclature for tethering tracts that are part of the spectrum of occult spinal dysraphic lesions.

METHODS: The tethering tract in 20 patients with spina bifida occulta underwent histological examination with H & E staining and epithelial membrane antigen (EMA) immunolabeling, and additional selected specimens were stained with Masson trichrome.

RESULTS: All tethering tracts contained fibrous connective tissue. Four tracts were lined with epithelial cells and either originated within a dermoid cyst, terminated at a skin dimple/sinus opening, or had both of these characteristics. No tethering tracts exhibited EMA positivity or meningeal elements. Although all tethering tracts originated in juxtaposition to the spinal cord, their termination sites were variable.

CONCLUSIONS: Based on histological findings and presumed embryological origin, the authors broadly classified tethering tracts terminating within the dura mater, epidural space, or lamina as "short tethering tracts" (STTs). The STTs occurred mostly in conjunction with split cord malformations and had a purely fibrous composition. Tethering tracts terminating superficial to the overlying lamina were classified as "long tethering tracts" (LTTs), and the authors propose that these are embryologically distinct from STTs. The LTTs were of two varieties: epithelial and nonepithelial, the former being typically associated with a skin dimple or spinal cord (epi)dermoid cyst. In fact, analysis of the data suggested that not every tethering tract terminating in or on the skin should be classified as a dermal sinus tract without histological confirmation, and because no evidence of meningeal tissue-lined tracts was detected, the use of the term "meningocele manqué" may not be appropriate.

PMID: 17877266

Hyperglycemic condition disturbs the proliferation and cell death of neural progenitors in mouse embryonic spinal cord

Gao Q, Gao YM. Hyperglycemic condition disturbs the proliferation and cell death of neural progenitors in mouse embryonic spinal cord. International Journal of Developmental Neuroscience. 2007 Aug 19;

Spina bifida, which results from failure of fusion in the spinal region of neural tube, is among the most common birth defects associated with diabetic pregnancy. However, the mechanism underlying maternal diabetes-induced congenital malformations including spina bifida is not fully understood. It was hypothesized that hyperglycemic conditions affect the proliferation and apoptosis of neural progenitor cells in the developing spinal neural tube, leading to abnormal neurodevelopment. In the present study, biological processes such as proliferation and apoptosis were investigated in the neuroepithelial cells of the developing spinal neural tube of embryos from diabetic mice, and in embryonic spinal neural tube derived neural progenitor cell cultures exposed to high glucose in vitro. Maternal diabetes caused decreased proliferation and increased apoptosis of the neuroepithelial cells in the developing spinal cord of embryos from diabetic mouse. Decreased proliferation and increased apoptosis were also found in neural progenitor cells exposed to high glucose. In addition, high glucose-induced apoptosis in neural progenitor cells was associated with activation of caspase-3. Thus, high glucose disturbs both proliferation and cell death of neural progenitors in the developing spinal neural tube. This could provide a cellular mechanism by which maternal hyperglycemia induces spina bifida in embryos from diabetic pregnancy.

PMID: 17888615