Haemophilus influenzae and Streptococcus pneumoniae infections in children with cerebrospinal fluid shunts.

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.

Combined pressure-radionuclide evaluation of suspected cerebrospinal fluid shunt malfunction: a seven-year clinical experience.

A simple, safe radionuclide technique for evaluating the functional status of a cerebrospinal fluid shunt has been used in the clinical management of hydrocephalus in 306 patients over a seven-year period. Results of 526 studies showed greater than 99% sensitivity and accuracy in diagnosing distal shunt obstruction and 96% correct correlation with clinical outcome overall. Intrareservoir pressure measurements are especially valuable to diagnose proximal catheter shunt malfunction and to assess shunt dependency.

Gram-negative cerebrospinal fluid shunt-associated infections.

Twenty hydrocephalic children with cerebrospinal fluid (CSF) shunts over an 11-year period were seen with Gram-negative central nervous system (CNS) infections. Seventeen infections were with single organisms and three were mixed. Sixteen of 20 (80%) of the infections occurred within five months of shunt surgery. Complete shunt removal or replacement in a new site plus systemic and intraventricular antibiotics resulted in a 100% (9/9) cure rate. Systemic and intraventricular antibiotics alone or in combination with incomplete shunt removal generally were unsuccessful. Significant morbidity and mortality were associated with these infections. Of the 18 patients with follow-up data, seven (39%) died with the infection, four (22%) sustained definite CNS damage, three (17%) were retarded after infection but their preinfection status was unknown, and only four (22%) patients escaped without definite sequela. Early recognition and appropriate therapy, hopefully, will improve the current bleak prognosis

Follow-up comparison of hydrocephalus with and without myelomeningocele.

A series of 454 hydrocephalic patients with and without myelomeningocele and with and without treatment is reviewed. The survival rates for hydrocephalus alone and for hydrocephalus with myelodysplasia are comparable. The authors reach the conclusion that treatment of the hycrocephalic process and its complications is the most critical therapeutic consideration. Mental retardation is the major unalterable cause for failure to develop independence; some lesser emotional causes can be modified by encouragement. Repeated reassessment of the patient's condition and adjustment are important. Before treatment is started parents or guardians should be fully informed of the child's future potential for independent life and mental development.

Developmental guidelines for children with myelodysplasia.

A new inventory of 166 milestones and developmental tasks was designed and given to parents of 173 children with myelodysplasia to use over a 2 1/2-year period to record their children's development. The inventory included items in the categories of self-help (including independent toileting), personal-social development, and gross motor development. The children were placed in one of four subgroups according to their level of paralysis. For each motor-level group, the percentage of those performing each item at various ages was calculated. The ages of routine performance of selected self-help and personal-social items are reported for 20, 50, and 80 percent achievement for the children for whom the data were known. There was a tendency for the less paralyzed children to learn skills more quickly than their more paralyzed peers. However, the wide age ranges within groups for learning individual skills indicate that factors other than the level of paralysis affect the rate of development, and these factors need to be identified. The data provided represent a reasonable estimate of when children with varying degrees of paralysis can first be expected to perform developmental tasks. The tables can be used to establish learning objectives and programs so that more children with myelodysplasia can learn independence at an earlier age.

The natural history of hip deformity in myelomeningocele.

We studied 1061 children with myelomeningocele, reviewing 3184 pelvic radiographs from 802 patients. Hip dislocation had occurred by the age of 11 years in 28% of children with a thoracic neurosegmental level, 30% of those with an L1/2 level, 36% of L3, 22% of L4, 7% of L5 and only 1% of those with sacral levels. Hip dislocation was not inevitable even when there was maximal muscle imbalance about the hip. The average hip flexion contracture in children aged 9 to 11 years was significantly greater in those with thoracic (22 degrees) and L1/2 (33 degrees) levels than in those with L4 (9 degrees), L5 (5 degrees) or sacral (4 degrees) levels. Our findings indicate that muscle imbalance is not a significant factor in the production of flexion deformity or dislocation of the hip; both are commonly seen in the absence of imbalance. The restoration of muscle balance should no longer be considered to be the principal aim of the management of the hip in children with myelomeningocele.

Epidemiology, etiologic factors, and prenatal diagnosis of open spinal dysraphism.

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.

Anatomy of the spinal cord in patients with meningomyelocele with and without hypoplasia or hydromyelia.

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.

Longevity of patients born with myelomeningocele.

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.

Epidemiology of tethered cord with meningomyelocele.

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.

Plasma homocysteine and methionine concentrations in children with neural tube defects.

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.

The outcome of fetal myelomeningocele brought to term.

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.

19-year follow-up of fetal myelomeningocele brought to term.

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.

Comparison of erythrocyte antioxidant enzyme activities and embryologic level of neural tube defects.

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.

The management of patients with cerebrospinal fluid shunts.

This article outlines the principles of management of the patient with a cerebrospinal fluid shunt, emphasizing the clinical and laboratory methods of determining shunt malfunction or infection. Appropriate therapies for each complication are described.

Cognitive abilities and lipomyelomeningocele.

Ten children with lipomyelomeningocele were evaluated with the WISC--R, the Wide Range Achievement Test--Revised, the Developmental Test of Visual-motor Integration, and the Child Behavior Checklist. These children were consecutive referrals to a birth defects clinic. Unlike their meningomyelocele counterparts, as a group these children appear to be average in their intellectual, academic, and behavioral characteristics. However, they exhibited low average perceptual motor skills, a feature more commonly seen in meningomyelocele.

Myelodysplasia: the natural history of kyphosis and scoliosis. A preliminary report.

The results of this study support the concept that the levels of the bifid vertebral arch and of functional motor activity are significant influences on the development of scoliosis and kyphosis in patients born with myelodysplasia. 'Significant' degrees of scoliosis and kyphosis may appear at any time during life, but most frequently occur during late childhood or adolescence. Not all 'significant' curvatures require treatment, nor do all children with myelodysplasia and factors predisposing to kyphosis and scoliosis develop these complications. It is believed that the preliminary cumulative percentage curves presented in this study will be of value in counselling parents of afflicted newborn infants, and in planning the management of patients born with myelodysplasia.

Assessing the development of daily living skills in patients with spina bifida.

The development of independence in daily living skills of 256 patients with spina bifida was assessed by means of a new Functional Activities scoring system. The score was derived from nine categories of activity; five are to do with self-care, three with locomotion and one with social interaction. The reasons for the variation in achievement between individuals with the same degree of paralysis are discussed, as are the differences in learning curves for single activities. The scoring system enables a quantitative assessment to be made of the current status of an individual patient, and enables more realistic therapeutic goals to be set.