Infantile Patients Research Articles

Safety and Accuracy of Pedicle Screws and Constructs Placed in Infantile and Juvenile Patients

Retrospective review. To determine the safety of pedicle screws placed in infantile and juvenile patients younger than 10 years of age, and to evaluate the accuracy and the incidence of short and long-term (>2-year follow-up) complications for the screws and construct utilized. Although much has been written regarding the use of pedicle screws for the treatment of adult and adolescent spinal deformities, few studies have examined complication rates with regard to pedicle screws placed for pediatric spinal deformities in patients younger than 10 years of age. Eighty-eight patients treated with 948 pedicle screws placed for a variety of pediatric spinal deformities were performed at a single institution. We evaluated the accuracy of pedicle screw placement via radiographic review by two spinal surgeons not involved in the surgical treatment. The average age at surgery was 6.8 year (range, 1 + 11 to 9 + 11 year). Five hundred ninety-four pedicle screws were placed in the thoracic spine and 354 screws in the lumbar spine. Three screws (0.32%) violated the lateral wall of the pedicle, two screws (0.21%) violated the inferior wall, and three screws (0.32%) were suspected of medial wall violation for a total of eight screws (0.84%) malpositioned. Although short-term complications occurred in nine patients (10.2%) (four-wound infection, two-foot drop, two-respiratory problems, first-sixth cranial nerve palsy), there were no insertion or short-term complications specifically related to the use of pedicle screws. Long-term complications occurred in nine patients (10.2%) (three-deformity progression, four-growing rod breakage), whereas two patients required revision surgery because of pullout and prominence of proximal thoracic pedicle screws (n = 4) placed in growing rod constructs (2.3% of patients, 0.4% of screws). There were no intraoperative or short-term pedicle screw insertion-related complications and a very low long-term complication rate (2.3% of patients, 0.4% of screws) specifically related to the use of pedicle screws in infantile and juvenile spinal deformity patients. More than 99% of screws were accurately placed.

Surgery of infantile spasms with tuberous sclerosis

Objective To investigate the surgical indications, methods and outcomes of infantile spasms with tuberous sclerosis(TS). Method Surgical treatment of 17 infantile spasms patients with TS was reviewed. Single epileptogenic tuber or lobe was resected when a focal epileptic discharge was indicated according to preoperative evaluation and EcoG, and multiple lobes or tubers resection were chosen to deal with hemisphere limited multiple epileptic foci. Anterior corpus callosotomy was added when contralateral hemisphere showed epileptic discharges. Results Acording to follow - up of 3 years in average after surgery, 11 patients had an Engel Class Ⅰ outcome, 4 patients had rare seizure ( Engel Class Ⅱ ), and 2 patients had a reduction in seizure frequency (Engel Class Ⅲ ). The mean IQ of patients was improved from 52.6 to 61. 8. Conclusions Epilepsy surgery in tuberous sclerosis with infantile spasms showes a favourable outcome,and surgical intervention should be considered in some intractable infantile spasms after corresponding tuber is derermined. Key words: Intractable epilepsy; Tuberous sclerosis; Spasms, infantile; Surgical procedures, operative

Severe muscle damage following viral infection in patients with Fukuyama congenital muscular dystrophy

Fukuyama congenital muscular dystrophy (FCMD), which is characterized by cortical migration defect and eye abnormalities, is the most common subtype of CMD in Japan. Fukutin (FKTN), the responsible gene for FCMD, encodes a protein involved in the glycosylation of alpha-dystroglycan. We have experienced some patients with FCMD who showed sudden exacerbation of muscle weakness with marked elevation of serum creatine kinase (CK) and urinary myoglobin levels a few days after a febrile episode of viral infection, occasionally leading to death. To describe this peculiar phenomenon, we focused on 12 patients who developed a sudden exacerbation of muscle weakness among 96 genetically defined FCMD patients and hospitalized because of a febrile illness at Tokyo Women’s Medical University between 1997 and 2008. All the 12 patients were homozygous for a 3-kb insertion mutation of FKTN. The patients developed exacerbation of muscle weakness ranging from paralysis to loss of head control. The onset was concentrated in summer, and coxsackieviruses and enteroviruses were most often detected, especially in infantile patients. Eight of the 12 patients were treated with corticosteroids and recovered within 2weeks. Four patients were treated without steroid, and needed 18.5days on mean for improvement. None developed renal failure. The reason for muscle damage induced by viral infection remains unknown; however, physicians should consider its risk, sometimes leading to death, and draw it to parents’ attention, especially in the defervescent stage.

Treatment Outcome of Pompe Disease Infants with Negative Cross-Reactive Immunologic Material From Israel and Gaza

Infantile Pompe disease is a fatal autosomal recessive lysosomal storage disease caused by deficiency of acid alpha glucosidase (GAA). Patients are either unable to form the native enzyme [cross reactive immunologic material (CRIM)–negative patients], or they synthesize non-functional protein designated CRIM–positive patients. Enzyme replacement therapy with recombinant human GAA (rhGAA) prolongs survival in infantile Pompe patients. However, long-term retrospective analysis revealed that CRIM–negative status is associated with poorer clinical outcome and reduced overall survival mediated, in part by development of early and high serotiters of antibody to the exogenous protein.

Treatment Guidelines for Pompe Disease: A South European Perspective

Pompe disease is a rare lysosomal disorder of muscle glycogen metabolism due to -glucosidase (acid maltase) eficiency. The prevalence of the disease is estimated to be 1:40,000. The diagnosis is based on the identification of the specific biochemical defect and has to be confirmed by molecular genetic analysis. Since 2006, enzyme replacement therapy (ERT) for Pompe disease has been available in Southern Europe. Several countries in Southern Europe are allowed, once the diagnosis is confirmed, to perform ERT and its costs are fully supported by the Ministries of Health. For example, to our knowledge, either in Portugal or Italy, the drug reimbursement is based on a specific treatment programme which removes those costs from the hospital budget. Since 2006, AIFA (Agenzia Italiana del Farmaco) has approved alglucosidase(Myozyme) for the treatment of Pompe disease patients in Italy, either for infantile or late-onset patients. Authorisation to treat patients with ERT has to be given by a centre specialising in rare diseases. This centre must assess the diagnosis of Pompe disease with absolute certainty before starting treatment. In 2008, a group of leading Italian Pompe disease researchers reviewed, from a multidisciplinary point of view, the current practices in diagnosis, management and treatment of Pompe disease. The main criteria for starting ERT ncludes: (1) confirmed diagnosis; (2) symptoms and clinical signs of muscle weakness; (3) in cases of asymptomatic yperCKaemia, a 6-month follow up has been suggested in an attempt to monitor possible clinically relevant hanges suggesting treatment. In summary, our standard protocol mainly includes evaluation of muscle strength, respiratory assessment and keletal muscle MRI. We have studied over 80 patients treated with ERT coming from 18 different Italian centres ccording to this protocol. In a recent meeting on Pompe disease held in the Netherlands, researchers showed great interest in trying to ssess new criteria for early diagnosis of Pompe disease. In our opinion, there is an emerging role for neuroimaging based on new quantitative techniques (more precise valuation of muscle fat fraction), that should allow an earlier detection of muscle damage in Pompe patients and consequent early start of ERT.

Study of Muscle Autophagy and Atrophy Markers in Different Phenotypes of Pompe Disease

ntroduction: As reported recently, massive accumulation of autophagic debris appears to contribute greatly to keletal muscle weakness in Pompe disease. im, Methods: We studied muscle autophagy and atrophy markers in 3 infantile-onset and 15 late-onset Pompe atients. Furthermore, we compared data from 3 adult-onset patients with data from a second skeletal muscle iopsy, taken at 6–10 years of disease progression and after enzyme replacement therapy (ERT) in an infantile and n a juvenile-onset patient. esults: Our results indicate that the infantile-onset patients constitute a homogeneous group, not only for what oncerns clinical severity but also autophagic impairment and atrophic rate. All infantile patients show induction f autophagy and of ubiquitin proteasome systems. Vacuolated/engulfed fibers display autophagy-related atrophy, uggesting a key role of impaired autophagy and subsequent autophagosomes accumulation in myofibrillar disoranization and alteration of endocytic trafficking. Conversely, late-onset patients appear to have heterogeneous features, although the majority of them show nduction of autophagy and atrophy as well. Interestingly, the presence of p62 positive aggregates correlate pretty ell with myofiber atrophy. In general, the degradation systems appear to be still functioning in these patients and eem to contribute positively to counteract disease progression. Comparison of different staged biopsies from the same patient evidenced a marked induction of autophagy and trophy with disease progression, and seems to indicate that in advanced stages of the disease detrimental vicious echanisms are generated that lead to myofiber impairment. Conversely, analysis of muscle biopsies after ERT videnced a decreased expression of autophagy and atrophy markers, indicating a possible beneficial effect of herapy. onclusion: Present data underline the role of unproductive autophagy and accumulation of aggregate-prone biquitinated proteins in the pathogenesis of Pompe disease, especially in more severely affected patients.

CYP1B1-Related Anterior Segment Developmental Anomalies : Novel Mutations for Infantile Glaucoma and Von Hippel's Ulcer Revisited

To determine the prevalence of CYP1B1 mutations in a cohort of patients with congenital corneal opacification (CCO), infantile glaucoma, or both and to describe a developmental CCO associated with CYP1B1 mutation that may explain von Hippel's original description of an internal ulcer.Retrospective genotyping of a cohort of patients with infantile glaucoma and CCO.Thirty-three patients with CCO, infantile glaucoma, or both.All patients underwent a full clinical evaluation with or without examination under anesthetic including anterior segment photography, ultrasound biomicroscopy (for CCO patients; n = 22), and histopathologic analysis in patients in whom penetrating keratoplasty (PK) was performed (n = 10). Patient DNA and DNA from 50 normal control individuals who had undergone a full ophthalmologic examination were screened for CYP1B1 mutations.Classification of the developmental corneal opacity phenotype in infantile glaucoma patients with CYP1B1 mutations.Nine distinct pathogenic recessive CYP1B1 mutations were found in 11 patients from 6 unrelated families, including 1 patient with an entire deletion of the CYP1B1 gene. Two of these patients, including the patient with the deletion, had isolated infantile congenital glaucoma with no other abnormalities. No CYP1B1 mutations were found in another 13 patients (7 of whom underwent PK in at least 1 eye) who had CCO with iridocorneal or keratolenticular adhesions (Peters' anomaly types I and II, respectively). Eight further children with CYP1B1 mutations who had CCO from birth and glaucoma underwent successful glaucoma treatment but had persistent diffuse CCO without iridocorneal or keratolenticular adhesions. Three of these underwent bilateral PK, and the histologic results were not consistent with any hitherto recognized congenital corneal dystrophy and showed abnormalities of the central corneal endothelium.Both severe CCO and isolated infantile glaucoma are associated with CYP1B1 mutations. The severe CCO phenotype reported herein often requires PK and has typical histopathologic changes. The mutations associated with this phenotype have not been reported previously. This phenotype may explain the patient described by Von Hippel in 1897.

Propranolol for the Treatment of Orbital Infantile Hemangiomas

To evaluate the treatment of orbital infantile hemangiomas with systemic (oral) propranolol. This study was a retrospective observational case series of 5 infants who were diagnosed with orbital infantile hemangiomas between March and July of 2009. The average age at presentation was 3.1 months (3 weeks to 9 months). The patients received oral propranolol, with dosage varying among study centers. The patients were treated for an average of 7.1 months. Treatment of 5 infantile hemangioma patients with oral propranolol produced a significant reduction in the size of the hemangioma in 4 (80%) of the patients and a minimal improvement in one patient. No patient had significant adverse events during the treatment period. Oral propranolol may be an effective treatment for orbital infantile hemangiomas.

Early Infantile Onset ‘‘Congenital’’ Rett Syndrome Variants: Swedish Experience Through Four Decades and Mutation Analysis

The early infantile onset ''congenital'' variant of Rett syndrome presents with deviations of behavior from very early infancy. Here, we report on a clinical-genetic study in a collected series of 14 Swedish girls with early infantile onset Rett syndrome phenotype. The clinical diagnosis was based on symptom onset before the age of 6 months and the patients fulfilled 3 or more Rett variant criteria and 5 or more supportive criteria. Genotype-phenotype correlation studies in the CDKL5-gene have recently shown clinical associations to early infantile onset Rett variants. Mutation analyses for both the MECP2-gene and the CDKL5-gene were, therefore, performed. Of interest, we found a large deletion covering 2 exons in MECP2, which underlines the importance of MECP2 mutation screening even for the ''atypical'' early infantile onset variants of Rett syndrome. No early infantile onset Rett syndrome patients in this study had the previously well-known hotspot mutations in the MECP2-gene.

Initial Experience With a Multidisciplinary Strategy for Initiation of Propranolol Therapy for Infantile Hemangiomas

To outline a safe, standardized protocol for outpatient initiation of propranolol therapy for infantile hemangiomas. Retrospective review. Academic tertiary care pediatric hospital. Forty-nine infantile hemangioma patients were offered propranolol therapy and included in the study. Any patients requiring hospital admission were excluded. Screening consisted of cardiology evaluation, including electrocardiography and, when indicated, echocardiography. Target initiation dose was 2 to 3 mg/kg/d divided into 3 doses. Blood pressure and heart rate were initially monitored at baseline and 1 and 2 hours in clinic following initial dosing. A 3-hour time point was later added. Families received standardized instructions regarding home heart rate monitoring, side effects, and fasting. Outpatient propranolol therapy was safely initiated in 39 of 44 patients (89%). Five patients required brief admission: 1 with clinical signs/symptoms of heart failure, 3 having airway involvement, and 1 for social reasons. Propranolol administration transiently reduced blood pressure; the maximal decrease occurred at 2 hours, prompting addition of a 3-hour time point to ensure recovery. No patients exhibited symptomatic hypotension, bradycardia, or heart failure. In most children with infantile hemangiomas, propranolol therapy can be safely initiated as an outpatient. Careful cardiovascular evaluation by an experienced clinician is essential for pretreatment evaluation, inpatient admission (when necessary), blood pressure and heart rate monitoring following initial dosing, and parent education. This standardized multidisciplinary outpatient initiation plan reduces the cost of initiating therapy compared with inpatient strategies while still providing appropriate monitoring for potential treatment complications. Further evaluation of propranolol therapy efficacy at the current dosing and duration of treatment continues.

Novel mutation of TCIRG1 and clinical pictures of two infantile malignant osteopetrosis patients

Infantile malignant osteopetrosis (IMO) (OMIM 259700) is a lethal autosomal recessive disease. The underlying gene in most IMO patients is TCIRG1. This codes for the TCIRG1 protein involved in the cellular proton pump, which is highly expressed on surfaces of osteoclasts. We have characterized a family comprising two affected siblings born to healthy parents. The sister and her younger brother both presented classical X-ray images of IMO at 17 h and 16 weeks, respectively, after birth, and both died after the appearance of fever and flu-like symptoms months later. Radiographs revealed normal bone density in both parents. Mutation detection of the TCIRG1 gene was performed in the boy and the parents. The novel mutation c.242delC (p.Pro81ArgfsX85) and the known mutation c.1114C>T (p.Gln372X) were both identified in the boy. Both mutations are predicted to introduce premature stop codons, with deletion of 666 amino acids from the C terminus of the TCIRG1 protein of one allele and 459 from the other. Both mutations involve loss of part or the whole of the ATPase V0-complex domain of the protein. The father carries the c.242delC (p.Pro81ArgfsX85) mutation and the mother the c.1114C>T (p.Gln372X). Our findings provide new data for pre- and post-natal genetic diagnosis and identification of heterozygous carriers of the disease.

Clinical Evaluation of AG-1 Cream (Topical Antipruritic Moisturizing Agent) in Infantile Patients with Xerotic Dermatoses

Clinical Evaluation of AG-1 Cream (Topical Antipruritic Moisturizing Agent) in Infantile Patients with Xerotic Dermatoses

Clinical Features and the Risk Factors of Infantile Exotropia Recurrence

To evaluate the clinical features and the risk factors of recurrence in infantile exotropia. Retrospective, observational case series. The clinical records of 20 infantile exotropia patients who underwent exotropia surgery were reviewed retrospectively. Patients were divided into 2 groups according to the amount of exodeviation present at 1 year after surgery. Preoperative patient characteristics and postoperative alignments were evaluated at 1 day and 1, 3, 6, and 12 months after surgery. The successful group was composed of 12 patients with an alignment of less than 10 prism diopters (PD) of exodeviation, and the recurrent group was composed of 8 patients with an alignment of 10 PD or more of exodeviation (range, 10 to 18 PD) at 1 year after surgery. The incidences of dissociated vertical deviation, inferior oblique overaction, and rates of constancy before operation were not significantly different in the 2 groups (P = .603, P = .158, and P = .347, respectively), and postoperative deviations were not significantly different at 1 day after surgery. However, postoperative deviations were significantly different in the 2 groups at 1 month (P = .069) and 3 months (P < .001) after surgery, and this difference was maintained at 12 months after surgery. Furthermore, correlation between initial alignments at 1 month after surgery and final alignments was significant in successful group (P = .012). No single factor affecting the surgical outcome was identified in infantile exotropia, but the recurrence of infantile exotropia was apparent from the first postoperative month.

Successful treatment of acute angioedema attacks with a bradykinin receptor-2 antagonist (Icatibant) in a patient with acquired C1 inhibitor deficiency

Immune modulation with rituximab, methotrexate, and intravenous immunoglobulin (IVIG) has shown great success in inducing immune tolerance in a large cohort of enzyme replacement therapy (ERT)-naïve infantile Pompe disease patients. Antibody-dependent cellular cytotoxicity, the principal mechanism by which rituximab depletes B-cells, requires CD20 binding by Fab’2 of rituximab on B-cells and the concomitant binding of its Fc region to Fc receptors on effector cells or to complement. To protect patients against microbial infections when using rituximab, IVIG was added to the immunomodulation regimen used in Pompe disease. Administration of IVIG can saturate neonatal Fc receptors (FcRn), which recycle endogenous as well as administered polyclonal/monoclonal antibodies via the binding of the Fc moiety to FcRn. As such, the administration of IVIG prior to rituximab, a chimeric mouse-human monoclonal antibody, may sharply reduce the half-life of rituximab and in turn, its efficacy. Based on this understanding, it is vital to understand the optimal timing of IVIG administration in relation to rituximab administration for the purposes of inducing immune tolerance.

Hearing loss in Pompe disease revisited: results from a study of 24 children.

Little information is available regarding the auditory function in Pompe patients. Hearing loss has been reported in classic infantile patients, but it is still unknown whether central nervous system involvement interferes with auditory function and whether enzyme replacement therapy can improve hearing. Auditory function has not been studied in children with milder forms of the disease. We analyzed repetitive auditory brainstem response measurements and pure tone audiometry in 24 children with Pompe disease. Only 1 of 13 patients with milder phenotypes showed recurrent conductive hearing loss, while 10 out of 11 classic infantile patients had sensorineural hearing defects. These patients also had a high prevalence of conductive hearing loss. Five patients showed evidence of mild retrocochlear pathology, suggestive of glycogen accumulation in the central nervous system. Hearing loss persisted during therapy in all patients. The results emphasize the need for careful monitoring of auditory function in classic infantile Pompe patients, and for early implementation of hearing aids to protect speech and language development.

Alexander Disease Mutant Glial Fibrillary Acidic Protein Compromises Glutamate Transport in Astrocytes

Alexander disease (AxD) is a leukodystrophy caused by heterozygous mutations in the gene for glial fibrillary acidic protein, an intermediate filament protein expressed by astrocytes. The mutation causes prominent protein aggregates inside astrocytes; there is also loss of myelin and oligodendrocytes and neuronal degeneration. We show that immunohistochemical staining for glutamate transporter 1, the major brain glutamate transporter expressed primarily in astrocytes suggests decreased levels in the hippocampi of infantile AxD patients. A knock-in mouse model of AxD also shows significant reduction of glutamate transporter 1 in the hippocampus. To explore this phenomenon at the cellular level, wild-type and R239C mutant glial fibrillary acidic proteins (the most common mutation) were overexpressed in astrocytes in culture. Western blotting and whole-cell patch clamp recordings demonstrated that the R239C astrocytes exhibited markedly reduced glutamate transporter 1 protein levels; this resulted in attenuated or abolished glutamate-induced inward transporter current. Neurons cocultured with the R239C astrocytes exhibited increased death after glutamate challenge. These results indicate that aberrant astrocytes have decreased glutamate uptake, which may play an important role in the pathogenesis of neuronal and oligodendrocyte injury and death in AxD.

Congenital myotonic dystrophy can show congenital fiber type disproportion pathology

Congenital myotonic dystrophy (CDM) is associated with markedly expanded CTG repeats in DMPK. The presence of numerous immature fibers with peripheral halo is a characteristic feature of CDM muscles together with hypotrophy of type 1 fibers. Smaller type 1 fibers with no structural abnormality are a definitive criterion of congenital fiber type disproportion (CFTD). Nonetheless, we recently came across a patient who was genetically confirmed as CDM, but had been earlier diagnosed as CFTD when he was an infant. In this study, we performed clinical, pathological, and genetic analyses in infantile patients pathologically diagnosed as CFTD to evaluate CDM patients indistinguishable from CFTD. We examined CTG repeat expansion in DMPK in 28 infantile patients pathologically diagnosed as CFTD. Mutation screening of ACTA1 and TPM3 was performed, and we compared clinical and pathological findings of 20 CDM patients with those of the other cohorts. We identified four (14%) patients with CTG expansion in DMPK. ACTA1 mutation was identified in four (14%), and TPM3 mutation was found in two (7%) patients. Fiber size disproportion was more prominent in patients with ACTA1 or TPM3 mutations as compared to CFTD patients with CTG expansion. A further three patients among 20 CDM patients showed pathological findings similar to CFTD. From our results, CDM should be excluded in CFTD patients.

PAS‐positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease

Screening of blood films for the presence of periodic acid-Schiff (PAS)-positive lymphocyte vacuoles is sometimes used to support the diagnosis of Pompe disease, but the actual diagnostic value is still unknown. We collected peripheral blood films from 65 untreated Pompe patients and 51 controls. Lymphocyte vacuolization was quantified using three methods: percentage vacuolated lymphocytes, percentage PAS-positive lymphocytes, and a PAS score depending on staining intensity. Diagnostic accuracy of the tests was assessed using receiver operating characteristic (ROC) curves. All three methods fully discerned classic infantile patients from controls. The mean values of patients with milder forms of Pompe disease were significantly higher than those of controls, but full separation was not obtained. The area under the ROC curve was 0.98 for the percentage vacuolated lymphocytes (optimal cutoff value 3; sensitivity 91%, specificity 96%) and 0.99 for the percentage PAS-positive lymphocytes and PAS score (optimal cutoff value 9; sensitivity 100%, specificity 98%). Our data indicate that PAS-stained blood films can be used as a reliable screening tool to support a diagnosis of Pompe disease. The percentage of PAS-positive lymphocytes is convenient for use in clinical practice but should always be interpreted in combination with other clinical and laboratory parameters.

Relationship Between Visual Acuity and Foveation Window in Infantile Nystagmus by Analyzing Nystagmus Waveforms

Purpose: To report herein on Nystagmus Acuity Estimator Function (NAEF) based on the foveation time, obtained by analyzing waveforms of infantile nystagmus patients and comparing the results with the patients' actual visual acuity. Methods: Electro-oculographic data of 27 patients with infantile nystagmus were reviewed. Data of patients only with jerk type nystagmus and reliable visual acuity were analyzed. The foveation time was measured, and NAEF was calculated and compared with the patients' actual best corrected visual acuity. Results: A correlation analysis of the patients' best corrected visual acuity with NAEF was performed, and the retrieved coefficient was 0.4266. The p-value calculated using the Pearson correlation coefficient was 0.0282, implying that high NAEF correlates positively with visual acuity. Conclusions: Estimated visual acuity, calculated based on the waveforms, positively correlates with the patients' actual visual acuity with statistical significance. However, since the foveation time can be measured only in the patients with jerk-type nystagmus waveforms, further study should be performed on the measurement of the foveation time with other waveforms. Furthermore, the present study shows that such analysis is possible with electrooculogram settings in most general hospitals.

Morphometric Analysis of Neurocentral Synchondrosis Using Magnetic Resonance Imaging in the Normal Skeletally Immature Spine

Morphometric analysis of the neurocentral synchondrosis (NCS) using magnetic resonance imaging in the normal infantile and juvenile patients. To assess the developmental stages of the neurocentral synchondrosis (NCS) by determining the age at which closure of the NCS occurs at specific levels of the spine and to evaluate whether symmetric growth of the NCS occurs during the different developmental stages in normal immature spine. The function and developmental stage of the NCS are controversial because of a lack of agreement on the exact age of closure. To date, most authors believe that the NCS is actively open at a very early age, but the reported age of closure of the NCS varies from age 3 to 16 years. This various closure age of the NCS has resulted in some confusion about the role of the NCS in the normal spinal growth or the development of spinal deformity. A total of 34 normal pediatric patients who had axial magnetic resonance images from first thoracic vertebra to fifth lumbar vertebra were assigned into following 3 groups: infantile group (n = 11), 0 to 3 years of age; juvenile-young group (n = 16), 4 to 7 years of age; and juvenile-old group (n = 7), 8 to 10 years of age. T2-weighted axial magnetic resonance images were used to analyze the NCS developmental stages using a custom 6-point scale (0: actively open with 0% closure; 5: 100% NCS closure). For the stage 0 closure NCS, the width and thickness of the NCS were measured. The NCS was actively open without closure for all less than 4-year-old patients at all levels. The NCS had approximate 75% closure in the lumbar region at 4 years of age while the thoracic NCS remained nearly open. After 5 years of age, the middle-lower thoracic NCS began to close with closure rate less than 25%. At the 10 years of age, the NCS in the lumbar region had near 100% closure, whereas the thoracic NCS demonstrated approximate 50% closure. For the NCS without closure, the average width and thickness were 7.6 x 1.3 mm on the left and 7.9 x 1.3 mm on the right, which was not significantly different. For the NCS with closure, the left and right NCS closure rates were not significantly different. The NCS developmental stage is age- and vertebral level-dependent. The NCS closes from the lumbar and proximal thoracic spine to the middle-distal thoracic spine and times from very early juvenile to the adolescent. The NCS symmetry bilaterally occurred not only during the active open, but also the long closure period. The NCS symmetric open and/or closure may be important to maintain the normal spine alignment.