OBJECTIVE:This paper reviews the frequency of central nervous system infections due to Haemophilus influenzae and Streptococcus pneumoniae associated with cerebrospinal fluid (CSF) shunts in pediatric patients. The need for immunizations in this patient population is also evaluated.PATIENTS:All patients with cerebrospinal fluid shunts except those with brain tumors seen in our clinics.METHODS:We reviewed data in three computer databases, kept prospectively recording details of CSF shunt procedures and CSF shunt-related infections.RESULTS:1,226 patients underwent 3,889 shunt placements between 1957 and 2007. Twelve patients had 14 episodes of Haemophilus or pneumococcal infections.CONCLUSIONS:Children with CSF shunts are at high risk for infection with H. influenzae and S. pneumoniae. Routine immunizations during infancy in addition to the 23-valent polysaccharide pneumococcal vaccine should be highly and actively encouraged by health care providers caring for children with CSF shunts. Additional expanded-coverage vaccines should be utilized if and when they become available.

This study describes ages of acquisition (AOA) of typical adolescent autonomy skills in a regional cohort of individuals with myelomeningocele (MM), aged 12 to 18 years, with a mean age of 14 years 11 months (SD 2y 5mo). Prospectively collected data over 10 years were analyzed. Regression analysis, using Generalized Estimation Equation, provided 50th centile and 75th centile AOA for each skill. One hundred and fifty-eight participants (90 males, 68 females) attended 378 annual patient visits. Patient contacts were equally distributed across age and physical severity groupings. Twenty-four percent of participants had functional lesion levels at or above L2, and 38% between L3-L5, 38% at S1 or below. Eighty-four percent had shunted hydrocephalus, 24% were independent in ambulation, and 69% achieved toileting independence before adolescence. AOA for autonomy skills were delayed by 25 to 30% when compared with typically developing adolescents. Differences in cognitive ability explained the variance in median ages for skill acquisition (p=0.01) more than physical lesion level. Participants acquired community skills at a median age of 16 years 6 months. Twelve percent of 18-year-olds drove cars (9% with supervision, 3% independently), regardless of physical lesion severity. We conclude that adolescents with MM acquire the majority of autonomy skills 2 to 5 years later than their typically developing peers. This study establishes AOA timelines for autonomy skills in adolescents with MM.

The objectives of this study were to extend survival analysis into adulthood for patients with myelomeningocele (MM) and to compare survival curves for patients born with varying defect severity before and after 1975. We have reviewed existing data for 904 patients with MM seen in a large multidisciplinary children’s clinic over 43 years. Before 1975, a major contributor to decreased survival is death during infancy. The presence of cerebral spinal fluid shunting is a major contributor to increased survival. After 1975, survival to adolescence is similar regardless of shunt status (p = 0.17). For all patients alive at age 16, a significant decrease in survival probability after age 34 years was found for individuals with shunted hydrocephalus compared to those without a shunt (p = 0.03). Although childhood survival for individuals born after 1975 is not related to shunt status, adults with MM and shunted hydrocephalus may be at risk for decreased longevity.

It is with great pleasure and appreciation of the honor that I present this 44th year of the Society for Research into Hydrocephalus and Spina Bifida Presidential address. I thank both the Executive Committee of, and the Society itself, for providing me this opportunity to serve you over the past three years. My objeetives for these three years were: 1) publicize the prevention of neural tube defects, 2) identify and develop solutions to the problems of adults born with 'Spina Biflda' and 3) involve representatives of the third-world nations and younger persons in our Society. By sponsoring this meeting, the Center for Prevention and Disease Control ofthe Federal Government of the United States has given us the financial resourees to achieve these goals. Thank you.

There are limited data concerning the life expectancy for individuals born with myelomeningocele (MM), with and without hydrocephalus. To ascertain such data was our first purpose. We have selected all patients with MM in our computer database, The Patient Data Management System (PDMS/fx). Data were transferred to Excel for primary and SPSS/PC for final analysis by Kaplan-Meier life survival curves. Of the 1,054 patients with MM in the Birth Defects Clinic and the University of Washington Medical Center (UWMC) of Seattle, 505 are now over the age of 21 (391) or have died (114). Follow-up information was available since 1994 for 132, 62% of whom we have had contact within the past 2 years. The second purpose was to identify potential health factors associated with long-term outcome of patients with MM. Patient variables chosen as relevant to survival included hydrocephalus, treatment before or after 1975, and health maintenance determined by outcome for those receiving care within the last 5 years or those last seen before. Age at last appointment and reason for visit were determined in order to identify age-specific health care needs of the adult population. Survival and medical needs were obtained from the UWMC's computer database, Mindscape, and by telephone survey for adult patients not seen in the last 2 years. Death is more frequent earlier in life for those MM patients with hydrocephalus. Ordinary degenerative disorders affect MM patients earlier in life than normals. Our data extend life expectancy for patients with MM and hydrocephalus to age 40 years with some reliability for those treated from 1957 to 1974, but only 24 years for those treated with modern techniques after 1974. More data is needed to determine long-term survival.

We conducted a 19-year follow-up study of 223 infants with myelomeningocele born by cephalic presentation, 68 born by pre-rupture of amniotic membranes cesarean section (PRAM C/S) and 155 born vaginally to determine outcome. We recorded radiographic level as the last intact vertebral arch at the cephalad end of the spinal defect from standard AP films of the spine. Protrusions of the lesions dorsal to the back were obtained from medical records or parental recall. Subsequent spinal cord abnormalities (hydromyelia, tethered cord and hypoplasia) were determined by patient's symptoms and verified by MRI. Data were from our Patient Data Management System and analyzed using Microsoft Excel and Epi Info 6. Flat lesions protruding less than 1.0 cm beyond the plane of the back and those associated with breech position or kyphus were not benefited by PRAM CIS (Fisher's Exact, p = 0.58 between the two types of delivery for motor level). Flat lesions were more common in the vaginally delivered group (p = 0.01). Lesions protruding equal to 1.0 cm or beyond were associated with less paralysis after PRAM C/S (p = 0.01). Although tethered cord syndrome was more common in the PRAM C/S group (p = 0.02), there was no difference in the muscle strength loss between the PRAM C/S and the vaginally delivered groups. Symptomatic hydromyelia was equally distributed but spinal cord hypoplasia was more common in the PRAM C/S group (p = 0.03). Due to the limited numbers of patients in each group available for analysis, we recommend further study to ascertain the appropriate management of fetal myelomeningocele diagnosed in utero and brought to term.

We examined 17 years of experience with 238 patients with meningomyelocele without kyphosis or cephalopelvic disproportion as an indication of cesarean section delivery. Sixty-four of 84 (64/84) patients born by cesarean section before rupture of the amniotic membranes, with or without labor, exceeded the proportion of similar, minimally paralyzed patients born by cesarean section after rupture of the amniotic membranes (20/38; X-2 = 5.7, df = 1, P = 0.02) and after vaginal birth (65/115; X-2 = 7.8, df = 1, P = 0.005). From 1982 to 1987, the incidence of newborns born with meningomyelocele (25-48 per year) exceeded the numbers born from 1988 to 1996 (7-20; T = 6.2, df = 13, P = 0.00003). Cesarean section delivery before rupture of the amniotic membranes apparently indicates a more favorable outcome for infants diagnosed with meningomyelocele and movement of their legs in utero. However, more study is required to further define the degree of protrusion of nerves, placode, and meningomyelocele sac beyond the dorsal plane of the back, and whether breech presentation or spinal cord hypoplasia adversely affect infant outcome despite cesarean section delivery before rupture of the amniotic membranes.

This chapter describes the anatomy of the spinal cord in children born with meningomyelocele, and reviews co-morbidities following the primary repair of meningomyeloceles. Data from 654 cases of meningomyelocele have been drawn from a computerized database, Patient Data Management System/fx [16]. We have also performed computer-assisted analysis of magnetic resonance imaging (MRI) studies of the spinal cord. This chapter describes the anatomy of the spinal cord of 41 patients examined by 67 MRI studies from a total of 83 patients. All cases were selected because they experienced symptoms compatible with a tethered cord and had had a neurosurgical procedure. An additional five were diagnosed with spinal cord hypoplasia. Tethered cord symptoms were related to local scarring, and improved following surgical release for 62 of the 83 postmeningomyelocele repair patients. Of the symptoms of the other 21 patients, 16 were relieved by other operations (e.g., CSF shunt repair) and five were not subjected to an untethering procedure because of a diagnosis of spinal cord hypoplasia. Etiologies other than, or in addition to, tethering included an obstructed cerebrospinal fluid shunt, syringohydromyelia, and benign tumor, as well as spinal cord hypoplasia. The areas of spinal cords were determined from axial MRI by digitized cross sections of 23 vertebral levels of the 41 patients and five normal controls. These studies differentiated very small, symptomatic spinal cords from the spinal cords of symptomatic and asymptomatic syringohydromyelia as well as from spinal cords of patients with spinal cord tethering. Collaborative, multicenter studies of larger numbers of patients are recommended.

Computerized patient clinical abstracts for 3196 subjects from a total of 3616 were studied. All patients from each of four centers (National Children's Hospital in Buenos Aires, Children's Memorial Hospital of Chicago, Royal Children's Hospital in Melbourne, and Children's Hospital in Seattle), born between 1965 and 1996, were included. Significant differences in the number of patients in each center were found according to type of spina bifida, age,level of lesion, type of birth, and ability to walk. Despite large numbers of patients, restriction of analyses for proportion able to walk by age, and level of lesion yielded such small numbers in each cell as to render analyses questionable. The authors recommend that a larger number of centers should join an International Myelodysplasia Study Group, begin a collection of data according to common definitions, utilize the computerized Patient Data Management System, and initiate prospective collaborative studies.

We compared the cross-sectional areas of spinal cords of patients with normal cords to the area of patients with meningomyelocele. The control group consisted of examinations of 27 patients with normal spinal cords providing 1547 axial images at 20 levels, C2-L2. The meningomyelocele group consisted of 67 MRI examinations of 41 patients, providing 4,095 axial images at 23 levels C2 to S1. Thirty-four examinations were of 21 patients with minimal hydromyelia, 7 examinations were of 3 patients with operable hydromyelia, and 26 examinations were of 17 patients without hydromyelia. In an additional analysis, we selected those meningomyelocele patients with cord tethering but without hydromyelia or hypoplasia (53 examinations of 30 patients) and compared them to symptomatic hypoplasia cases (9 examinations of 6 patients). The symptomatic hypoplasia cases were chosen because of progressive loss of muscle strength and worsening spasticity not relieved by surgical adhesiolysis. The test, retest error was 5.6% with differences between the means of repeated readings not being significant. All tests for significance were paired T test. The areas of spine levels C7-L2 for the controls were significantly larger than for the meningomyelocele patients (p = 0.000007). Including all levels C2-S1, the minimal hydromyelia cases were not significantly different from those without hydromyelia (p = 0.5). The areas C2-S1 of operable hydromyelia cases were larger than both non-shunted minimal hydromyelia (p = 0.00009) and of meningomyelocele patients without hydromyelia (p = 0.00003). The areas C7-L2, of hypoplasia cases were significantly smaller compared to the "normal" meningomyelocele cases (p = 0.0004). These data suggest that hydromyelia stimulates overgrowth of the cord, as does hydrocephalus of the brain, and that adhesiolysis procedures are of no value with hypoplasia of the spinal cord.

This paper describes the epidemiology of tethered cord syndrome and its etiologies and co-morbidities following initial repair of both meningomyeloceles and lipomeningomyelocele. A review of the pertinent literature and data from 654 cases of meningomyelocele and 118 cases of lipomeningomyelocele has been drawn from a computerized database, Patient Data Management System/fx. Only cases born since 1964 were analyzed for the etiologies, co-morbidities, spinal cord abnormalities detected by contrast studies or MRI and for significant symptoms and signs. Tethered cord symptoms were related to an attachment to a rigid tether for all 31 cases following lipomeningomyelocele repair but 62 (75%) of the 83 post meningomyelocele repair patients developed the symptoms of tethered cord. Causes other than, or in addition to, tethering included an obstructed cerebrospinal fluid shunt, syringohydromyelia, benign tumor and spinal cord hypoplasia. Quantitative differentiation between asymptomatic thin spinal cords and symptomatic spinal cord hypoplasia as well as between central canal enlargement and symptomatic syringohydromyelia could not be demonstrated. Collaborative, multi-center studies of larger numbers of patients are recommended.

Mild to moderate homocysteinemia in women has been associated with an increased frequency of pregnancies with neural tube defects (NTD). Homocysteinemia is also an independent risk factor for premature vascular disease. In addition to folic acid, supplemental Vitamin B12, Vitamin B6 and betaine may normalize homocysteine metabolism, decrease the risk for NTD formation, and correct related metabolic imbalances in children with NTD. By means of automated amino acid analysis, we assessed total non-fasting homocysteine and methionine in plasma from 24 children with myelomeningocele. This study group (mean age 10.5 +/- 4.9 years) included 12 girls and 12 boys randomly selected from our Birth Defects Clinic. Homocysteine concentrations in our patients (4.7 +/- 1.8 mumol/L) did not differ from those of 20 randomly selected child controls (5.1 +/- 2.6 mumol/L). The mean homocysteine concentration for 36 adult controls (9.3 +/- 3.0 mumol/L) was significantly higher than the mean for either group of children (p < 0.0001). Linear regression analysis revealed negative correlation of total plasma homocysteine with serum folate (r = -0.53; p = 0.01), but not of homocysteine with either methionine or B12. Plasma methionine concentrations from our patients did not differ from adult reference values. Elevated homocysteine in some mothers of children with NTD has been attributed to defective methylation of homocysteine. These preliminary results do not indicate such a defect in the children themselves. A more comprehensive study of homocysteine, methionine and related metabolites in children with NTD and age-matched controls will be required to determine the clinical significance of these findings.

Erythrocyte free radical scavenging enzyme activities and their cofactor trace elements in plasma were assessed in 26 selected patients with myelomeningocele, both parents from 10 selected families, and 14 healthy adult controls. All index children except one were deficient in erythrocyte glutathione peroxidase (GSH-Px). Nine of 10 parent pairs had at least one parent with deficient GSH-Px activity. Children with myelomeningocele had significantly lower GSH-Px activities than their parents; the group of 10 parent pairs had significantly lower GSH-Px activities than the control group; and glutathione reductase activities were significantly lower in parents and children with myelomeningocele compared with controls. A deficiency in one or more antioxidant enzymes may increase the risk for neural tube defects.

The caudal neural tube closes late in the first month after fertilization and failure of it results in myelomeningocele. Epidemiologic studies have shown differences in prevalence at birth based on ethnic-racial backgrounds and geography. Etiologic factors include the drug valproic acid or carbamazepine. Periconceptional folic acid supplementation appears to decrease the prevalence of neural tube defects. Numerous modalities allow for prenatal diagnosis of myelomeningocele. A cesarean section, before rupture of amniotic membranes and onset of labor, decreases the degree of paralysis.

Increased exposure to oxidant-derived free radicals or inadequate systems for antioxidant defense could alter cellular response at critical points in development. We measured 5 antioxidant enzymes, glutathione peroxidase (GSH-Px), glutathione reductase, glutathione-S-transferase, catalase and superoxide dismutase in erythrocytes and their plasma cofactor trace elements (Se, Zn, Cu) in 37 children with myelomeningocele and in 37 age-matched controls. We placed the patients into 3 groups according to motor level of the lesion at birth. We found significantly lower GSH-Px activities (p = 0.007) in children with myelomeningocele. For paired comparisons among the 3 patient groups and controls, there were significant differences (p < 0.05) between controls and both high (thoracic) and raid (lumbar) level embryologic lesions. The finding of antioxidant enzyme variations in our patients with myelomeningocele may indicate a role for abnormal oxidative metabolism in the development of this defect. The contribution of oxidative stress to human birth defects warrants investigation. We discuss potential relationships between oxidative stress and energy metabolism during primary neurulation.

14 years experience with 354 infants born with myelomeningocele are reviewed in view of prelabor and pre-rupture of amniotic membranes vs vaginal delivery or delivery by cesarian section after labor and rupture of amniotic membrane. The apparent lack of effect of severity of impairment determined by prenatal diagnosis on parental decision to carry their baby to term, the negative effect on motor function of kyphos or congenital kyphoscoliosis, the equivocal effect of breech presentation with or without rupture of amniotic membranes and the beneficial effect of prelabor and prerupture of membranes delivery of selected infants is discussed. The need for further multiple center, collaborative study to identify the contribution of a number of factors influencing the outcome of fetuses diagnosed as having myelomeningocele is emphasized.