CASE REPORT
Scoliosis in Children With Aicardi Syndrome Emmanouil Grigoriou, MD, Jessica Jo DeSabato, BA, Dino Colo, MD, and John P. Dormans, MD, FACS
Background: Aicardi syndrome (ACS) is a rare neurodevelopmental disorder that was classically characterized by the triad of agenesis of corpus callosum, infantile spasms, and chorioretinal lacunae. As new cases emerge and new common phenotypic features are being described in subsequent reports, new modified diagnostic criteria have been proposed that now classify the observed costovertebral abnormalities as supporting diagnostic features. To our knowledge there are no previous studies focusing and describing the scoliosis observed in children with ACS. Methods: We screened billing lists to identify patients seen in the Division of Orthopaedic Surgery at our institution with a diagnosis of ACS that were treated for scoliosis after 2001. A total of 5 patients were identified. Medical records and radiographs were retrospectively reviewed in all cases. In all of the patients the diagnosis of ACS had been confirmed through complete genetic evaluation and advanced imaging. Results: The mean age when scoliosis was first noticed was 3.9 ± 4.2 years (range, 0.5 to 10.5 y) with a mean Cobb angle of 22.5 ± 6.7 degrees (range, 10 to 27 degrees). The mean age at the first orthopedic visit was 5.8 ± 5.0 years (range, 1.5 to 13 y) with a progressed mean Cobb angle of 39.5 ± 17.3 degrees (range, 15 to 57 degrees). Congenital vertebral anomalies were observed in 1 patient. Three patients were treated surgically; 1 of the 3 patients had a surgical complication with loss of intraoperative neuromonitoring signals. Two patients had not undergone surgery at the last visit with a mean Cobb angle of 75.5 degrees. The mean postoperative follow-up for the surgical group (cases 1 to 3) was 3 ± 3.6 years (range, 0.6 to 7.2 y) and the mean total follow-up for both groups was 6.6 ± 2.5 years (range, 2.6 to 8.6 y). Conclusions: Scoliosis in ACS can represent a clinically significant problem that is underdiagnosed and overshadowed by the other severe medical complications associated with the syndrome. Our data suggest that scoliosis in patients with ACS is rapidly progressive and bracing is ineffective; early screening, close observation, and low threshold for referral to an orthopedic surgeon are crucial. Level of Evidence: Level IV—case series. Key Words: Aicardi syndrome, ACS, corpus callosum agenesis, scoliosis, congenital, neuromuscular
From the Division of Orthopaedic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA. The authors declare no conflicts of interest. Reprints: John P. Dormans, MD, FACS, The Division of Orthopaedic Surgery, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, 3401 Civic Center Boulevard, Philadelphia, PA 19104. E-mail: [email protected]. Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
e38 | www.pedorthopaedics.com
(J Pediatr Orthop 2015;35:e38–e42)
A
icardi syndrome (ACS) was first described briefly in 1965 and fully in 1969 by Aicardi.1 It occurs exclusively in females or individuals with Klinefelter syndrome (XXY) and although it appears to be an X-linked dominant disorder, no gene or candidate regions of the X chromosome have been identified yet leading to ACS being a purely clinical diagnosis. Although the exact incidence and prevalence of ACS is unknown, epidemiologic studies from the United States and Sweden have reported incidence of 1 per 99,000 live births to 1 per 167,000 live births.2,3 The prevalence of ACS is approximated to be between 539 and 853 cases in the United States.2 Since 2001 at our institution only 29 patients with ACS have been documented, either as a 1-time visit to the Emergency Department, for an initial genetic, neurologic, or ophthalmologic evaluation, or for continuous follow-up throughout our various divisions. ACS was classically defined as the triad of complete or partial agenesis of the corpus callosum, chorioretinal lacunae, and infantile spasms. Over the past 15 years, in part due to the use of modern imaging techniques, additional features have been described and ACS is now recognized as a complex neurodevelopmental disorder with multiple neuronal and extraneuronal features.1,2,4,5 On the basis of that, Sutton et al6 proposed new modified diagnostic criteria in 2006; besides the original classic triad, the existence of 2 classic features and at least 2 other major or supporting features were also strongly suggestive of an ACS diagnosis. The major features are classified as cortical brain malformations, optic disc/nerve coloboma, cysts around the third cerebral ventricle, and periventricular and subcortical heterotopia. Supporting features are vertebral and rib anomalies, “split-brain” EEG, gross cerebral hemispheric asymmetry, and vascular malformations. Although ACS has a wide spectrum of clinical presentation, its natural history is usually very poor with severe outcomes in terms of mental retardation and functional disability as well as high morbidity and mortality rates. A recent study by Kroner et al2 reported a survival of 62% at 27 years of age with a peak relative risk of death around 16 years of age. The prognosis is largely dependent on the severity of the clinical presentation of each patient as there is no curative treatment currently available other than managing the sequelae of the syndrome, underlying the J Pediatr Orthop
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 35, Number 5, July/August 2015
Copyright
r
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
N/A 10.2 y 1/5 = 20% 17 1.8 y 39.5 — 22.5 3.9 y Total mean
L lumbar 0.5 5, F
10
L thoracolumbar 28 1.5 4, F
ACS indicates Aicardi syndrome; CVA, congenital vertebral anomalies; F, female; L, left; PSFI, posterior spinal fusion with instrumentation; R, right.
1/3 = 33%
12
53.2
3y
8 y and 4 mo 6 y and 8 mo N/A 92 N/A 5 2.9 15
38
0.6
10
T5/T6 and T7/T8 bloc vertebrae None
10 None 25 3.7 52
Thoracolumbar 9.2 kyphosis Thoracic 2.1 kyphosis Thoracolumbar 3.4 kyphosis — 5.8 y R thoracolumbar 5.5 3, F
27
6 None 0 0 23 1.5 1.5 2, F
23
12
10
59
N/A
8 y and 8 mo 8y 7 y and 2 mo 58 18 Yes
8 mo 42 7 None
1 y and 2 mo 15 15 None
T2-L3 PSFI T3-L4 growing rods T3-pelvis unit Rod N/A 14.5 None 26/36 1.5 52/57 13
Thoracic kyphosis Normal Double (L thoracic/ R thoracolumbar) R thoracolumbar 10.5 1, F
26/21
Age Cobb (y) Angle
Type of Curve
Sagittal Contour
Age Cobb Time Cobb (y) Angle Interval (y) Angle
CVA
Surgery
Last Orthopedic Office Visit Progression From Referral to First Orthopedic Office Visit
2014 Wolters Kluwer Health, Inc. All rights reserved.
Patient, Sex
RESULTS We present our experience with 5 children with a diagnosis of ACS followed for scoliosis in the Division of Orthopedic Surgery at our institution. Table 1 presents a summary of the clinical and radiographic data collected. In 3 of 5 patients (cases 2, 4, 5) spinal asymmetry was noted before the age of 2 years. With the exception of 1 patient (case 2), the mean time interval between clinical or radiographic findings of spinal asymmetry and the first actual orthopedic office visit was 2.3 ± 1.2 years with a mean Cobb angle that had progressed 20.4 ± 12.7
TABLE 1. Summary of Clinical and Radiographic Data Collected on the 5 ACS Patients
METHODS We queried the billing lists maintained by our institution using ICD-9 codes to identify ACS patients who were seen in the Division of Orthopaedic Surgery for the treatment of scoliosis after 2001. This method yielded 5 patients. All patients had undergone complete genetic evaluation and confirmatory brain magnetic resonance imaging (MRI) testing. We retrospectively reviewed the medical charts and radiographs of all patients. We assessed all available radiographs for the documented reason for examination and the referring department to determine the specialist and the time that spinal asymmetry was first noticed and investigated. We documented the curve characteristics and progression and any observed vertebral anomalies in advanced imaging. The type of treatment was documented and the course of symptoms was noted for any compilations. Any additional musculoskeletal conditions were noted. The small number of patients allowed us to report only descriptive statistics.
Total Follow-up
crucial role of highly individualized long-term management. The core management of children with ACS has traditionally been performed by a highly specialized pediatric neurologist but with the newly recognized other features of the syndrome a multidisciplinary approach, including care by an orthopedic surgeon, is becoming increasingly important. Initially, scoliosis in ACS children was reported to be observed in as much as 1 in every 3 patients.7 However, more recent demographic studies report higher scoliosis rates of 64%8 and 55%5 in 14 and 67 children, respectively, and it is now believed that 50% of ACS patients develop scoliosis.1 Furthermore, hemivertebrae, blocked or fused vertebrae, and absent or malformed ribs are reported in 1 in 3 ACS patients.5,8 Given that these congenital costovertebral anomalies are now a supporting diagnostic criterion, the role of the orthopedic surgeon in this rare but expanding syndrome is critical. However, to the authors’ knowledge, there are no previous studies focusing on the treatment of scoliosis in ACS patients. The purpose of this study was to describe our experience with scoliosis in children with ACS, assess its progression, and characterize the curve patterns in an effort to underline the importance of the orthopedic manifestations in patients with this syndrome.
2 y and 7 mo 5 y and 10 mo
Scoliosis in Children With Aicardi Syndrome
Age Age Cobb Office (y) Procedure Complications (y) Angle Postoperative Visits
Volume 35, Number 5, July/August 2015
First Orthopedic Office Visit
Scoliosis Was First Noticed
J Pediatr Orthop
www.pedorthopaedics.com |
e39
J Pediatr Orthop
Grigoriou et al
Volume 35, Number 5, July/August 2015
FIGURE 1. Case 4: computed tomography scan of the chest on the upper left corner (A) and sagittal T2-weighted magnetic resonance imaging (MRI) of the spine on the lower left corner (B) showing bloc vertebrae at the T5/T6 and T7/T8 levels (arrows) and mild anterior wedging of the T1, T2, T3, and T4 vertebral bodies. On the right, anteroposterior x-ray of the spine (C) showing a 59-degree thoracolumbar curve. Off note, there is a small right pleural effusion, increased nonobstructive bowel gas pattern, and a gastrostomy tube overlying the upper abdomen.
degrees. All patients except 1 (case 5) received brace treatment with a Boston TLSO brace. Congenital vertebral anomalies were observed in case 4; bloc vertebrae were noted at the T5/T6 and T7/T8 levels (Fig. 1). All patients except 1 (case 2) had hip problems ranging from mild uncovering of the femoral heads (cases 4 and 5) to bilateral hip subluxations (case 3) and unilateral hip dislocation (case 1). One patient (case 1) had a double major curve pattern, (Fig. 2) 3 patients (cases 2 to 4) had a thoracolumbar curve pattern and 1 patient (case 5) had a lumbar curve. The mean postoperative follow-up for the surgical group (cases 1 to 3) was 3 ± 3.6 years (range, 0.6 to 7.2 y) and the total follow-up for both groups was 6.6 ± 2.5 years (range, 2.6 to 8.6 y).
DISCUSSION ACS is a rare congenital neurodevelopmental syndrome that presents almost exclusively in females and has a wide spectrum of clinical presentation. Although there are patients with milder expressions of this syndrome, usually ACS patients are severely disabled.
e40 | www.pedorthopaedics.com
All of our patients had a long medical history of either severe pulmonary complications because of their intractable epilepsy, requiring multiple hospitalizations and long-term antibiotics or even thoracoscopies for empyema drainage, or gastrointestinal complications because of their permanent mechanical feeding tubes. In accordance with previous reports, the most common medical complications in our 5 patients after seizures were constipation, upper and lower airway infections, and aspiration problems.5–7,9 Although there is a growing consensus regarding the factors that diminish everyday functionality and, more importantly, life expectancy in children with congenital neurologic disorders,10–12 orthopedic complications in these children often obtain a secondary importance and are overshadowed by their severe and life threatening medical issues. This is more prominent in syndromes with chronic and difficult to control seizures like Rett’s, Angelman, and Aicardi. Characteristically, although spinal asymmetry was first noticed, either clinically, on physical examination, or as an incidental finding on a chest x-ray, in our 5 patients at the mean age of 3.9 ± 4.2 years (range, 0.5 to 10.5 y) with a Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Orthop
Volume 35, Number 5, July/August 2015
Scoliosis in Children With Aicardi Syndrome
FIGURE 2. Case 1: preoperative (A and C) and 1-year postoperative (B and D), anteroposterior (A and B) and lateral (C and D) radiographs showing a 55-degree upper thoracic and 66-degree thoracolumbar curve preoperatively and posterior spinal fusion with pedicle screws of levels T2-L3 with intact implant placement and excellent curve correction postoperatively. Off note, there is a vagal nerve stimulator implanted as part of the patient’s antiepileptic treatment measures.
mean Cobb angle of 22.5 ± 6.7 degrees (range, 10 to 27 degrees) of the major curve and appropriate referral was made at that time, patients actually presented at the Spinal Center of our institution more than a year and a half later (1 y and 9 mo), with a major curve that had progressed approximately 17 ± 14.1 degrees (range, 0 to 36 degrees), measuring 39.5 ± 17.3 degrees (range, 15 to 57 degrees). This series of 5 patients demonstrates how difficult the timing for a surgical approach in these children is. Because of their late presentation to an orthopedic surgeon, the understandable hesitance of the families to undergo a major procedure and the fragile health state of the patients, which limits the period for surgery, planning any surgical approach in these children is a very challenging task. As a result, 2 of our patients were still treated conservatively at their last office visit, although they had major curves with a Cobb angle measuring 59 degrees (case 4) and 92 degrees (case 5). In addition, on the subject of surgical management of ACS patients, pelvic fixation of growing rods plays a significant role in correcting pelvic obliquity or obtaining adequate fixation in such rapidly progressive neuromuscular curves.13 Furthermore, interestingly, for patients born before 2000 (cases 1, 3, 5) the mean age of an orthopedic referral with a presumed diagnosis of scoliosis was at the age of 6 years and for patients born after 2000 (cases 2 and 4) at the age of 2 years. However, because of the small size of our series we cannot conclude, but only presume, that this correlates with the fact that within the last 15 years our knowledge about the syndrome and its physical manifestations has expanded significantly. Given the severe seizure activity of these children on a daily basis, bracing becomes a very daunting task for the families and as expected all of the 4 patients (cases 1 to 4) Copyright
r
treated with a brace were noncompliant constituting bracing as an ineffective treatment measure. Like bracing, serial Risser casting is an alternative intermediate treatment option to slow progression and delay surgery.14,15 However, in ACS patients, similarly to other patients with severe neurologic disorders, there are increased concerns for anesthesia-related complications and they require a highly specialized anesthesia team for every cast application. Regarding congenital vertebral malformations, in accordance with previous studies,5,8 only one of our patients had congenital scoliosis (case 4) with bloc vertebrae at 2 levels (T5/T6 and T7/T8) (Fig. 1).
CONCLUSIONS On the basis of our experience, our reported series and the existing literature,1,2,5,6 scoliosis is a serious complication of ACS that significantly limits the already fragile everyday quality of life of these patients. Orthopedic surgeons and related health care providers should be aware of this syndrome and its orthopedic associations. We believe that increased suspicion with careful clinical examination, screening early on with baseline x-rays of the spine for possible congenital vertebral anomalies and low threshold for referral to an orthopedic surgeon for musculoskeletal support and prevention of scoliosis-related complications are indicated. REFERENCES 1. Aicardi J. Aicardi syndrome. Brain Dev. 2005;27:164–171. 2. Kroner BL, Preiss LR, Ardini MA, et al. New incidence, prevalence, and survival of Aicardi syndrome from 408 cases. J Child Neurol. 2008;23:531–535.
2014 Wolters Kluwer Health, Inc. All rights reserved. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.pedorthopaedics.com |
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J Pediatr Orthop
Grigoriou et al
3. Palmer L, Zetterlund B, Hard AL, et al. Aicardi syndrome: presentation at onset in Swedish children born in 1975-2002. Neuropediatrics. 2006;37:154–158. 4. Sutton VR, Hopkins BJ, Eble TN, et al. Facial and physical features of Aicardi syndrome: infants to teenagers. Am J Med Genet A. 2005;138A:254–258. 5. Glasmacher MA, Sutton VR, Hopkins B, et al. Phenotype and management of Aicardi syndrome: new findings from a survey of 69 children. J Child Neurol. 2007;22:176–184. 6. Sutton VR, Van den Veyver IB. Aicardi Syndrome. In: Pagon RA AM, Ardinger HH, et al, eds. GeneReviewss [Internet]. Seattle (WA): University of Washington; 2006. [Updated 2012 Sep 20]. 7. Donnenfeld AE, Packer RJ, Zackai EH, et al. Clinical, cytogenetic, and pedigree findings in 18 cases of Aicardi syndrome. Am J Med Genet. 1989;32:461–467. 8. Menezes AV, MacGregor DL, Buncic JR. Aicardi syndrome: natural history and possible predictors of severity. Pediatr Neurol. 1994;11:313–318.
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Volume 35, Number 5, July/August 2015
9. Rosser TL, Acosta MT, Packer RJ. Aicardi syndrome: spectrum of disease and long-term prognosis in 77 females. Pediatr Neurol. 2002;27:343–346. 10. Rosenbloom L. Estimating life expectancy in children with neurological disabilities. Clinical Risk. 2004;10(no. 1):12–13. 11. Katz RT. Life expectancy for children with cerebral palsy and mental retardation: implications for life care planning. NeuroRehabilitation. 2003;18:261–270. 12. Hutton JL, Pharoah PO. Life expectancy in severe cerebral palsy. Arch Dis Child. 2006;91:254–258. 13. Sponseller PD, Yang JS, Thompson GH, et al. Pelvic fixation of growing rods: comparison of constructs. Spine (Phila Pa 1976). 2009;34:1706–1710. 14. Waldron SR, Poe-Kochert C, Son-Hing JP, et al. Early onset scoliosis: the value of serial Risser casts. J Pediatr Orthop. 2013;33:775–780. 15. Sanders JO, D’Astous J, Fitzgerald M, et al. Derotational casting for progressive infantile scoliosis. J Pediatr Orthop. 2009;29: 581–587.
Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Scoliosis in Children With Aicardi Syndrome Emmanouil Grigoriou, MD, Jessica Jo DeSabato, BA, Dino Colo, MD, and John P. Dormans, MD, FACS
Background: Aicardi syndrome (ACS) is a rare neurodevelopmental disorder that was classically characterized by the triad of agenesis of corpus callosum, infantile spasms, and chorioretinal lacunae. As new cases emerge and new common phenotypic features are being described in subsequent reports, new modified diagnostic criteria have been proposed that now classify the observed costovertebral abnormalities as supporting diagnostic features. To our knowledge there are no previous studies focusing and describing the scoliosis observed in children with ACS. Methods: We screened billing lists to identify patients seen in the Division of Orthopaedic Surgery at our institution with a diagnosis of ACS that were treated for scoliosis after 2001. A total of 5 patients were identified. Medical records and radiographs were retrospectively reviewed in all cases. In all of the patients the diagnosis of ACS had been confirmed through complete genetic evaluation and advanced imaging. Results: The mean age when scoliosis was first noticed was 3.9 ± 4.2 years (range, 0.5 to 10.5 y) with a mean Cobb angle of 22.5 ± 6.7 degrees (range, 10 to 27 degrees). The mean age at the first orthopedic visit was 5.8 ± 5.0 years (range, 1.5 to 13 y) with a progressed mean Cobb angle of 39.5 ± 17.3 degrees (range, 15 to 57 degrees). Congenital vertebral anomalies were observed in 1 patient. Three patients were treated surgically; 1 of the 3 patients had a surgical complication with loss of intraoperative neuromonitoring signals. Two patients had not undergone surgery at the last visit with a mean Cobb angle of 75.5 degrees. The mean postoperative follow-up for the surgical group (cases 1 to 3) was 3 ± 3.6 years (range, 0.6 to 7.2 y) and the mean total follow-up for both groups was 6.6 ± 2.5 years (range, 2.6 to 8.6 y). Conclusions: Scoliosis in ACS can represent a clinically significant problem that is underdiagnosed and overshadowed by the other severe medical complications associated with the syndrome. Our data suggest that scoliosis in patients with ACS is rapidly progressive and bracing is ineffective; early screening, close observation, and low threshold for referral to an orthopedic surgeon are crucial. Level of Evidence: Level IV—case series. Key Words: Aicardi syndrome, ACS, corpus callosum agenesis, scoliosis, congenital, neuromuscular
From the Division of Orthopaedic Surgery, The Children’s Hospital of Philadelphia, Philadelphia, PA. The authors declare no conflicts of interest. Reprints: John P. Dormans, MD, FACS, The Division of Orthopaedic Surgery, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, 3401 Civic Center Boulevard, Philadelphia, PA 19104. E-mail: [email protected]. Copyright r 2014 Wolters Kluwer Health, Inc. All rights reserved.
e38 | www.pedorthopaedics.com
(J Pediatr Orthop 2015;35:e38–e42)
A
icardi syndrome (ACS) was first described briefly in 1965 and fully in 1969 by Aicardi.1 It occurs exclusively in females or individuals with Klinefelter syndrome (XXY) and although it appears to be an X-linked dominant disorder, no gene or candidate regions of the X chromosome have been identified yet leading to ACS being a purely clinical diagnosis. Although the exact incidence and prevalence of ACS is unknown, epidemiologic studies from the United States and Sweden have reported incidence of 1 per 99,000 live births to 1 per 167,000 live births.2,3 The prevalence of ACS is approximated to be between 539 and 853 cases in the United States.2 Since 2001 at our institution only 29 patients with ACS have been documented, either as a 1-time visit to the Emergency Department, for an initial genetic, neurologic, or ophthalmologic evaluation, or for continuous follow-up throughout our various divisions. ACS was classically defined as the triad of complete or partial agenesis of the corpus callosum, chorioretinal lacunae, and infantile spasms. Over the past 15 years, in part due to the use of modern imaging techniques, additional features have been described and ACS is now recognized as a complex neurodevelopmental disorder with multiple neuronal and extraneuronal features.1,2,4,5 On the basis of that, Sutton et al6 proposed new modified diagnostic criteria in 2006; besides the original classic triad, the existence of 2 classic features and at least 2 other major or supporting features were also strongly suggestive of an ACS diagnosis. The major features are classified as cortical brain malformations, optic disc/nerve coloboma, cysts around the third cerebral ventricle, and periventricular and subcortical heterotopia. Supporting features are vertebral and rib anomalies, “split-brain” EEG, gross cerebral hemispheric asymmetry, and vascular malformations. Although ACS has a wide spectrum of clinical presentation, its natural history is usually very poor with severe outcomes in terms of mental retardation and functional disability as well as high morbidity and mortality rates. A recent study by Kroner et al2 reported a survival of 62% at 27 years of age with a peak relative risk of death around 16 years of age. The prognosis is largely dependent on the severity of the clinical presentation of each patient as there is no curative treatment currently available other than managing the sequelae of the syndrome, underlying the J Pediatr Orthop
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Volume 35, Number 5, July/August 2015
Copyright
r
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
N/A 10.2 y 1/5 = 20% 17 1.8 y 39.5 — 22.5 3.9 y Total mean
L lumbar 0.5 5, F
10
L thoracolumbar 28 1.5 4, F
ACS indicates Aicardi syndrome; CVA, congenital vertebral anomalies; F, female; L, left; PSFI, posterior spinal fusion with instrumentation; R, right.
1/3 = 33%
12
53.2
3y
8 y and 4 mo 6 y and 8 mo N/A 92 N/A 5 2.9 15
38
0.6
10
T5/T6 and T7/T8 bloc vertebrae None
10 None 25 3.7 52
Thoracolumbar 9.2 kyphosis Thoracic 2.1 kyphosis Thoracolumbar 3.4 kyphosis — 5.8 y R thoracolumbar 5.5 3, F
27
6 None 0 0 23 1.5 1.5 2, F
23
12
10
59
N/A
8 y and 8 mo 8y 7 y and 2 mo 58 18 Yes
8 mo 42 7 None
1 y and 2 mo 15 15 None
T2-L3 PSFI T3-L4 growing rods T3-pelvis unit Rod N/A 14.5 None 26/36 1.5 52/57 13
Thoracic kyphosis Normal Double (L thoracic/ R thoracolumbar) R thoracolumbar 10.5 1, F
26/21
Age Cobb (y) Angle
Type of Curve
Sagittal Contour
Age Cobb Time Cobb (y) Angle Interval (y) Angle
CVA
Surgery
Last Orthopedic Office Visit Progression From Referral to First Orthopedic Office Visit
2014 Wolters Kluwer Health, Inc. All rights reserved.
Patient, Sex
RESULTS We present our experience with 5 children with a diagnosis of ACS followed for scoliosis in the Division of Orthopedic Surgery at our institution. Table 1 presents a summary of the clinical and radiographic data collected. In 3 of 5 patients (cases 2, 4, 5) spinal asymmetry was noted before the age of 2 years. With the exception of 1 patient (case 2), the mean time interval between clinical or radiographic findings of spinal asymmetry and the first actual orthopedic office visit was 2.3 ± 1.2 years with a mean Cobb angle that had progressed 20.4 ± 12.7
TABLE 1. Summary of Clinical and Radiographic Data Collected on the 5 ACS Patients
METHODS We queried the billing lists maintained by our institution using ICD-9 codes to identify ACS patients who were seen in the Division of Orthopaedic Surgery for the treatment of scoliosis after 2001. This method yielded 5 patients. All patients had undergone complete genetic evaluation and confirmatory brain magnetic resonance imaging (MRI) testing. We retrospectively reviewed the medical charts and radiographs of all patients. We assessed all available radiographs for the documented reason for examination and the referring department to determine the specialist and the time that spinal asymmetry was first noticed and investigated. We documented the curve characteristics and progression and any observed vertebral anomalies in advanced imaging. The type of treatment was documented and the course of symptoms was noted for any compilations. Any additional musculoskeletal conditions were noted. The small number of patients allowed us to report only descriptive statistics.
Total Follow-up
crucial role of highly individualized long-term management. The core management of children with ACS has traditionally been performed by a highly specialized pediatric neurologist but with the newly recognized other features of the syndrome a multidisciplinary approach, including care by an orthopedic surgeon, is becoming increasingly important. Initially, scoliosis in ACS children was reported to be observed in as much as 1 in every 3 patients.7 However, more recent demographic studies report higher scoliosis rates of 64%8 and 55%5 in 14 and 67 children, respectively, and it is now believed that 50% of ACS patients develop scoliosis.1 Furthermore, hemivertebrae, blocked or fused vertebrae, and absent or malformed ribs are reported in 1 in 3 ACS patients.5,8 Given that these congenital costovertebral anomalies are now a supporting diagnostic criterion, the role of the orthopedic surgeon in this rare but expanding syndrome is critical. However, to the authors’ knowledge, there are no previous studies focusing on the treatment of scoliosis in ACS patients. The purpose of this study was to describe our experience with scoliosis in children with ACS, assess its progression, and characterize the curve patterns in an effort to underline the importance of the orthopedic manifestations in patients with this syndrome.
2 y and 7 mo 5 y and 10 mo
Scoliosis in Children With Aicardi Syndrome
Age Age Cobb Office (y) Procedure Complications (y) Angle Postoperative Visits
Volume 35, Number 5, July/August 2015
First Orthopedic Office Visit
Scoliosis Was First Noticed
J Pediatr Orthop
www.pedorthopaedics.com |
e39
J Pediatr Orthop
Grigoriou et al
Volume 35, Number 5, July/August 2015
FIGURE 1. Case 4: computed tomography scan of the chest on the upper left corner (A) and sagittal T2-weighted magnetic resonance imaging (MRI) of the spine on the lower left corner (B) showing bloc vertebrae at the T5/T6 and T7/T8 levels (arrows) and mild anterior wedging of the T1, T2, T3, and T4 vertebral bodies. On the right, anteroposterior x-ray of the spine (C) showing a 59-degree thoracolumbar curve. Off note, there is a small right pleural effusion, increased nonobstructive bowel gas pattern, and a gastrostomy tube overlying the upper abdomen.
degrees. All patients except 1 (case 5) received brace treatment with a Boston TLSO brace. Congenital vertebral anomalies were observed in case 4; bloc vertebrae were noted at the T5/T6 and T7/T8 levels (Fig. 1). All patients except 1 (case 2) had hip problems ranging from mild uncovering of the femoral heads (cases 4 and 5) to bilateral hip subluxations (case 3) and unilateral hip dislocation (case 1). One patient (case 1) had a double major curve pattern, (Fig. 2) 3 patients (cases 2 to 4) had a thoracolumbar curve pattern and 1 patient (case 5) had a lumbar curve. The mean postoperative follow-up for the surgical group (cases 1 to 3) was 3 ± 3.6 years (range, 0.6 to 7.2 y) and the total follow-up for both groups was 6.6 ± 2.5 years (range, 2.6 to 8.6 y).
DISCUSSION ACS is a rare congenital neurodevelopmental syndrome that presents almost exclusively in females and has a wide spectrum of clinical presentation. Although there are patients with milder expressions of this syndrome, usually ACS patients are severely disabled.
e40 | www.pedorthopaedics.com
All of our patients had a long medical history of either severe pulmonary complications because of their intractable epilepsy, requiring multiple hospitalizations and long-term antibiotics or even thoracoscopies for empyema drainage, or gastrointestinal complications because of their permanent mechanical feeding tubes. In accordance with previous reports, the most common medical complications in our 5 patients after seizures were constipation, upper and lower airway infections, and aspiration problems.5–7,9 Although there is a growing consensus regarding the factors that diminish everyday functionality and, more importantly, life expectancy in children with congenital neurologic disorders,10–12 orthopedic complications in these children often obtain a secondary importance and are overshadowed by their severe and life threatening medical issues. This is more prominent in syndromes with chronic and difficult to control seizures like Rett’s, Angelman, and Aicardi. Characteristically, although spinal asymmetry was first noticed, either clinically, on physical examination, or as an incidental finding on a chest x-ray, in our 5 patients at the mean age of 3.9 ± 4.2 years (range, 0.5 to 10.5 y) with a Copyright
r
2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Orthop
Volume 35, Number 5, July/August 2015
Scoliosis in Children With Aicardi Syndrome
FIGURE 2. Case 1: preoperative (A and C) and 1-year postoperative (B and D), anteroposterior (A and B) and lateral (C and D) radiographs showing a 55-degree upper thoracic and 66-degree thoracolumbar curve preoperatively and posterior spinal fusion with pedicle screws of levels T2-L3 with intact implant placement and excellent curve correction postoperatively. Off note, there is a vagal nerve stimulator implanted as part of the patient’s antiepileptic treatment measures.
mean Cobb angle of 22.5 ± 6.7 degrees (range, 10 to 27 degrees) of the major curve and appropriate referral was made at that time, patients actually presented at the Spinal Center of our institution more than a year and a half later (1 y and 9 mo), with a major curve that had progressed approximately 17 ± 14.1 degrees (range, 0 to 36 degrees), measuring 39.5 ± 17.3 degrees (range, 15 to 57 degrees). This series of 5 patients demonstrates how difficult the timing for a surgical approach in these children is. Because of their late presentation to an orthopedic surgeon, the understandable hesitance of the families to undergo a major procedure and the fragile health state of the patients, which limits the period for surgery, planning any surgical approach in these children is a very challenging task. As a result, 2 of our patients were still treated conservatively at their last office visit, although they had major curves with a Cobb angle measuring 59 degrees (case 4) and 92 degrees (case 5). In addition, on the subject of surgical management of ACS patients, pelvic fixation of growing rods plays a significant role in correcting pelvic obliquity or obtaining adequate fixation in such rapidly progressive neuromuscular curves.13 Furthermore, interestingly, for patients born before 2000 (cases 1, 3, 5) the mean age of an orthopedic referral with a presumed diagnosis of scoliosis was at the age of 6 years and for patients born after 2000 (cases 2 and 4) at the age of 2 years. However, because of the small size of our series we cannot conclude, but only presume, that this correlates with the fact that within the last 15 years our knowledge about the syndrome and its physical manifestations has expanded significantly. Given the severe seizure activity of these children on a daily basis, bracing becomes a very daunting task for the families and as expected all of the 4 patients (cases 1 to 4) Copyright
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treated with a brace were noncompliant constituting bracing as an ineffective treatment measure. Like bracing, serial Risser casting is an alternative intermediate treatment option to slow progression and delay surgery.14,15 However, in ACS patients, similarly to other patients with severe neurologic disorders, there are increased concerns for anesthesia-related complications and they require a highly specialized anesthesia team for every cast application. Regarding congenital vertebral malformations, in accordance with previous studies,5,8 only one of our patients had congenital scoliosis (case 4) with bloc vertebrae at 2 levels (T5/T6 and T7/T8) (Fig. 1).
CONCLUSIONS On the basis of our experience, our reported series and the existing literature,1,2,5,6 scoliosis is a serious complication of ACS that significantly limits the already fragile everyday quality of life of these patients. Orthopedic surgeons and related health care providers should be aware of this syndrome and its orthopedic associations. We believe that increased suspicion with careful clinical examination, screening early on with baseline x-rays of the spine for possible congenital vertebral anomalies and low threshold for referral to an orthopedic surgeon for musculoskeletal support and prevention of scoliosis-related complications are indicated. REFERENCES 1. Aicardi J. Aicardi syndrome. Brain Dev. 2005;27:164–171. 2. Kroner BL, Preiss LR, Ardini MA, et al. New incidence, prevalence, and survival of Aicardi syndrome from 408 cases. J Child Neurol. 2008;23:531–535.
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3. Palmer L, Zetterlund B, Hard AL, et al. Aicardi syndrome: presentation at onset in Swedish children born in 1975-2002. Neuropediatrics. 2006;37:154–158. 4. Sutton VR, Hopkins BJ, Eble TN, et al. Facial and physical features of Aicardi syndrome: infants to teenagers. Am J Med Genet A. 2005;138A:254–258. 5. Glasmacher MA, Sutton VR, Hopkins B, et al. Phenotype and management of Aicardi syndrome: new findings from a survey of 69 children. J Child Neurol. 2007;22:176–184. 6. Sutton VR, Van den Veyver IB. Aicardi Syndrome. In: Pagon RA AM, Ardinger HH, et al, eds. GeneReviewss [Internet]. Seattle (WA): University of Washington; 2006. [Updated 2012 Sep 20]. 7. Donnenfeld AE, Packer RJ, Zackai EH, et al. Clinical, cytogenetic, and pedigree findings in 18 cases of Aicardi syndrome. Am J Med Genet. 1989;32:461–467. 8. Menezes AV, MacGregor DL, Buncic JR. Aicardi syndrome: natural history and possible predictors of severity. Pediatr Neurol. 1994;11:313–318.
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9. Rosser TL, Acosta MT, Packer RJ. Aicardi syndrome: spectrum of disease and long-term prognosis in 77 females. Pediatr Neurol. 2002;27:343–346. 10. Rosenbloom L. Estimating life expectancy in children with neurological disabilities. Clinical Risk. 2004;10(no. 1):12–13. 11. Katz RT. Life expectancy for children with cerebral palsy and mental retardation: implications for life care planning. NeuroRehabilitation. 2003;18:261–270. 12. Hutton JL, Pharoah PO. Life expectancy in severe cerebral palsy. Arch Dis Child. 2006;91:254–258. 13. Sponseller PD, Yang JS, Thompson GH, et al. Pelvic fixation of growing rods: comparison of constructs. Spine (Phila Pa 1976). 2009;34:1706–1710. 14. Waldron SR, Poe-Kochert C, Son-Hing JP, et al. Early onset scoliosis: the value of serial Risser casts. J Pediatr Orthop. 2013;33:775–780. 15. Sanders JO, D’Astous J, Fitzgerald M, et al. Derotational casting for progressive infantile scoliosis. J Pediatr Orthop. 2009;29: 581–587.
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Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
