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Distal spinal cord pathology in the VATER association
Distal Spinal Cord Pathology By H.E. James,
R. Chesnut,
H. Krous,
in the VATER Association G. Billman,
K.L. Jones,
and M. Jones
San Diego, California 0 Herein the authors report the pathology of six cases of VATER association and tethered spinal cord that underwent operative intervention filum terminale and/or
for removal of lipomas of the conusrelease of the tethered cord. In five of
the six patients, the excised filum terminale consistently showed excessive mature adipose tissue, normal blood vessels, small myelinated
nerve fibers, and fibrous connec-
tive tissue. One patient had mature lobulated adipose tissue and vessels only. It is concluded that patients with the VATER association who present with distal spinal cord pathology consistently have abnormal involution of the filum terminale,
the
hallmark
being
an abnormal
collection
mature fat, thickening of the filum, and extension into the conus medullaris. Copyright
of
of the fat
B 1994 by W.B. Saunders Company
INDEX WORDS:
VATER association;
tethered
cord; lipoma,
conus-filum terminale.
S
PINAL DYSRAPHISM is an occult developmental disorder involving the dorsal median regions of the embryo, affecting the mesoderm and neuroectoderm, and at times, the ectoderm.‘” The physiopathology is either compression or traction, accompanied by tethering of the underlying neural e1ements.i~’ Clinically, it manifests as an insidious deterioration of the motor control of the lower extremities or urinary system.‘,“ It usually affects the distal cord.lJ The VATER association consists of a nonrandom association of multisystem structural defects.5-7 The findings are vertebral anomalies, anal atresia, esophageal atresia with tracheoesophageal fistula, and radial anomalies.h,7 Other strongly associated defects are renal anomalies, a single umbilical artery, and cardiac defects.8 Although there is significant morbidity and mortality early in life, once through the neonatal period these patients have a good prognosis8 In a previous report,’ we presented six cases with findings of spinal dysraphia in the lumbosacral region, which underwent confirmatory neuroimaging and subsequent operative neurosurgical intervention. The pathological findings of these six cases are the basis for this report. Previously, they all had been diagnosed as having the VATER association.”
MATERIALS
AND
METHODS
All six patients had either spinal ultrasonography or spinal magnetic resonance imaging that confirmed the presence of a low-set conus with a lipomatous tumor in the filum terminale and invading the conus. During surgery, all underwent release of the tethered cord and had carbon dioxide microsurgical radical resec-
JoUrnalofPed/arr/cSurgery,
Vol29,No
11 (November),1994:pp1501-1503
tion of the lipoma.” The specimens were formalin-forced, processed, embedded in paraffin, sectioned, and stained for routine light microscopy examination.
RESULTS
Histological studies of all the cases showed mature fatty tissue incorporated into the filum. In the majority, the fat was contained within but expanded and distended the filum terminale. The accompanying nerve filaments and blood vessels had a normal histological appearance (Fig 1). In one patient, mature lobulated fat extended beyond the filum terminale sheath and fused with the overlying subcutaneous tissues (lipomeningocele). The resultant subcutaneous mass lacked a distinct fibrous capsule (Fig 2). In all six patients, the fatty tissue extended into the conus, and the filum was more than 3 mm thick. The distal conus had varying degrees of distortion, produced by the adipose mass. A summary of the pathological findings is listed in Table 1. DISCUSSION
Spinal dysraphism may be considered a continuum in the malformations of myelomeningocele and spinal hamartomas.‘,3,4 If undiagnosed neonatally, it may present postnatally in an insidious manner, postnatally with progressive neurological dysfunction of the lower extremities or with urologic and rectal sphincter dysfunction, or in any combination of these.1-3 The underlying pathophysiology of the VATER association is unclear. Its value as a clinical entity lies in its recognition by the primary care physician, who may note one or two of the included defects and then attempt to detect or eliminate the other abnormalities. The more subtle the clinical findings, the more important their documentation. There is evidence that concordance exists between the VATER association and spinal dysraphism, in
From the Departments of Neurosciences {Neurosurgery Section) and Pathology, Children S Hospital San Diego, and the Divisions of Neurosurgery and Dysmotphology, Department of Pediatrics. School of Medicine, University of California, San Diego. CA. Date accepted: December 23, 1993. Suppotted in part by the Foundation for Pediatric and Laser Neurosurgery, Inc, a nonprqfit organization. Address reprint requests to H.E. James, MD, 7930 Frost St, Suite 304, San Diego. CA 92123. Copyright :B 1994 by WB. Saunders Company 0022-346819412911-0027$03.0010 1501
JAMES ET AL
Table 1. Spinal Pathology Peripheral
Fig 1. Cross-section of a filum terminale in one patient, demonstrating the excessive fat contained within the capsule. In the center is a normal blood vessel (artery of the filum), and scattered throughout are dark stained nerve filaments.
reports of the VATER association from other perspectives. Among a series of seven patients with the VATER association, one was reported to have spinal dysraphism.‘O In another series of 39 patients with the VATER association, one had a myelomeningocele and another had a spinal meningocele.8 Another report of diastomatomyelia and tethered cord in a patient with the VATER association” supports the association of VATER anomalies with spinal malformations involving the neuroectoderm.
Patient No.
Mature Fat
Fibrous Tissue
Myelinated
Fibers
VlXS&
1
+
+
+
2
+
+
+
+
+
3
+
+
+
+
4
+
+
+
+
5
+
+
6
+
+ _
+ _
Although the true incidence of spinal dysraphia in patients with the VATER association is unknown, current neuroimaging with spinal ultrasonography in the neonatal periodi2J3 and with magnetic resonance imaging at any age14,15permits a noninvasive diagnostic approach to these cases, which may yield a subpopulation of asymptomatic children with spinal dysraphia. The peculiar developmental aspects of the distal spinal column and cord may explain a higher association of dyraphic states at the lumbosacral level. This may be just part of another anomaly in the spectrum of the VATER association. The pathology of the spinal structures in this series is indicative of a primary mesodermal disorder of closure, which then involves the neuroectoderm to varying degrees. No dysplastic or malignant features were noted in any of the excised material. The excised elements were composed of mature cellular elements in an ectopic location or in excess. This was clearly demonstrated by the lipomas. A small amount of fat may be found in the histological analysis of normal filum terminale. However, an excess of fat, recognized as a “thickening” of the filum (of more than 3.0 mm in width) and the extension and “invasion” of the conus by the adipose tissue, is pathological. These histological changes are common to other lipomatous tumors of the conus.’ In spinal hamartomas, fat may be present, but it is always accompanied by other derivatives of the three primary layers and, not uncommonly, the fat is fetal, not mature (adult).16 Whether these histological findings reflect true neoplastic extension, or are simply an additional manifestation of disordered development, remains speculative. ACKNOWLEDGMENT
Fig 2. Section of the filum terminale of another patient, with disorganization and septations within the exhuberant fat. There is no mitotic activity. Dark staining of nerve filaments is seen.
The work.
authors
thank
Julie
Damschen
for excellent
secretarial
REFERENCES 1. James CCM, Lassman LP: Spinal dysraphism. Arch Dis Child 35315327,196O 2. James HE, Walsh JW: Spinal dysraphism. Curr Probl Pediatr ll:l-25, 1981 3. Lichenstein BW: Spinal dyraphism. Arch Neurol Psychiatr 44:792-809, 1940
4. Till K: Spinal dysraphism: A study of congenital malformations of the lower back. J Bone Joint Surg [Br] 51:415-422, 1969 5. Say B, Gerald PS: A new polydactyl, imperforate anus, vertebral anomalies syndrome. Lancet 2:688,1968 6. Say D, Balci S, Pirnay T, et al: A new syndrome of dysmorphogenesis-Imperforate anus associated with poly-oligodactyly and
SPINAL PATHOLOGY
AND VATER ASSOCIATION
skeletal (mainly vertebral) anomalies. Acta Paediatr Stand 60:197202,197l 7. Quan L, Smith DW: The VATER association, vertebral defects, anal atresia. T-E fistula with esophageal atresia, radial and renal dysplagia: A spectrum of associated defects. J Pediatr 82:104-106, 1973 8. Rintala R. Lindahl H, Louhima: VATER association and anorectal malformations. Z Kinderchir 41:22-26, 1986 9. Chesnut R, James HE, Jones KL: The VATER association and spinal dysraphia. Pediatr Neurosurg 18:144-148, 1992 10. Barry JE. Auldist AW: The VATER association: One end of the spectrum of anomalies. Am J Dis Child 128:76Y-771. 1974 Il. Lawhon SM. MacEwen GD, Bunnel WP: Orthopaedic aspects of the VATER association. J Bone Joint Surg [Br] 68:424-429. 19X6
1503
12. James HE, Scheible W. Kerber C, et al: Comparison of high resolution real time ultrasonography and high resolution computed tomography in an infant with dyraphism. Neurosurgery 13:301-305, 1983 13. Scheible W, James HE, Leopold CR, et al: Occult spinal dysraphism in infants: Screening with high resolution real-time ultrasound. Radiology 146:743-746, 1983 14. Hamgan WC, Wright SM. Wright RM: Clinical utility of magnetic resonance imaging in pediatric neurosurgical patients. J Pediatr 108522-529, 1986 15. Altman NR, Altman DH: MR imaging of spinal dysraphism. AJNR 8533-538. 1987 16. Tibbs PA, James HE, Rorke LB, et al: Midline hamartomas masquerading as meningomyeloceles or teratomas in the newborn infant. J Pediatr 89:928-933. 1976
R. Chesnut,
H. Krous,
in the VATER Association G. Billman,
K.L. Jones,
and M. Jones
San Diego, California 0 Herein the authors report the pathology of six cases of VATER association and tethered spinal cord that underwent operative intervention filum terminale and/or
for removal of lipomas of the conusrelease of the tethered cord. In five of
the six patients, the excised filum terminale consistently showed excessive mature adipose tissue, normal blood vessels, small myelinated
nerve fibers, and fibrous connec-
tive tissue. One patient had mature lobulated adipose tissue and vessels only. It is concluded that patients with the VATER association who present with distal spinal cord pathology consistently have abnormal involution of the filum terminale,
the
hallmark
being
an abnormal
collection
mature fat, thickening of the filum, and extension into the conus medullaris. Copyright
of
of the fat
B 1994 by W.B. Saunders Company
INDEX WORDS:
VATER association;
tethered
cord; lipoma,
conus-filum terminale.
S
PINAL DYSRAPHISM is an occult developmental disorder involving the dorsal median regions of the embryo, affecting the mesoderm and neuroectoderm, and at times, the ectoderm.‘” The physiopathology is either compression or traction, accompanied by tethering of the underlying neural e1ements.i~’ Clinically, it manifests as an insidious deterioration of the motor control of the lower extremities or urinary system.‘,“ It usually affects the distal cord.lJ The VATER association consists of a nonrandom association of multisystem structural defects.5-7 The findings are vertebral anomalies, anal atresia, esophageal atresia with tracheoesophageal fistula, and radial anomalies.h,7 Other strongly associated defects are renal anomalies, a single umbilical artery, and cardiac defects.8 Although there is significant morbidity and mortality early in life, once through the neonatal period these patients have a good prognosis8 In a previous report,’ we presented six cases with findings of spinal dysraphia in the lumbosacral region, which underwent confirmatory neuroimaging and subsequent operative neurosurgical intervention. The pathological findings of these six cases are the basis for this report. Previously, they all had been diagnosed as having the VATER association.”
MATERIALS
AND
METHODS
All six patients had either spinal ultrasonography or spinal magnetic resonance imaging that confirmed the presence of a low-set conus with a lipomatous tumor in the filum terminale and invading the conus. During surgery, all underwent release of the tethered cord and had carbon dioxide microsurgical radical resec-
JoUrnalofPed/arr/cSurgery,
Vol29,No
11 (November),1994:pp1501-1503
tion of the lipoma.” The specimens were formalin-forced, processed, embedded in paraffin, sectioned, and stained for routine light microscopy examination.
RESULTS
Histological studies of all the cases showed mature fatty tissue incorporated into the filum. In the majority, the fat was contained within but expanded and distended the filum terminale. The accompanying nerve filaments and blood vessels had a normal histological appearance (Fig 1). In one patient, mature lobulated fat extended beyond the filum terminale sheath and fused with the overlying subcutaneous tissues (lipomeningocele). The resultant subcutaneous mass lacked a distinct fibrous capsule (Fig 2). In all six patients, the fatty tissue extended into the conus, and the filum was more than 3 mm thick. The distal conus had varying degrees of distortion, produced by the adipose mass. A summary of the pathological findings is listed in Table 1. DISCUSSION
Spinal dysraphism may be considered a continuum in the malformations of myelomeningocele and spinal hamartomas.‘,3,4 If undiagnosed neonatally, it may present postnatally in an insidious manner, postnatally with progressive neurological dysfunction of the lower extremities or with urologic and rectal sphincter dysfunction, or in any combination of these.1-3 The underlying pathophysiology of the VATER association is unclear. Its value as a clinical entity lies in its recognition by the primary care physician, who may note one or two of the included defects and then attempt to detect or eliminate the other abnormalities. The more subtle the clinical findings, the more important their documentation. There is evidence that concordance exists between the VATER association and spinal dysraphism, in
From the Departments of Neurosciences {Neurosurgery Section) and Pathology, Children S Hospital San Diego, and the Divisions of Neurosurgery and Dysmotphology, Department of Pediatrics. School of Medicine, University of California, San Diego. CA. Date accepted: December 23, 1993. Suppotted in part by the Foundation for Pediatric and Laser Neurosurgery, Inc, a nonprqfit organization. Address reprint requests to H.E. James, MD, 7930 Frost St, Suite 304, San Diego. CA 92123. Copyright :B 1994 by WB. Saunders Company 0022-346819412911-0027$03.0010 1501
JAMES ET AL
Table 1. Spinal Pathology Peripheral
Fig 1. Cross-section of a filum terminale in one patient, demonstrating the excessive fat contained within the capsule. In the center is a normal blood vessel (artery of the filum), and scattered throughout are dark stained nerve filaments.
reports of the VATER association from other perspectives. Among a series of seven patients with the VATER association, one was reported to have spinal dysraphism.‘O In another series of 39 patients with the VATER association, one had a myelomeningocele and another had a spinal meningocele.8 Another report of diastomatomyelia and tethered cord in a patient with the VATER association” supports the association of VATER anomalies with spinal malformations involving the neuroectoderm.
Patient No.
Mature Fat
Fibrous Tissue
Myelinated
Fibers
VlXS&
1
+
+
+
2
+
+
+
+
+
3
+
+
+
+
4
+
+
+
+
5
+
+
6
+
+ _
+ _
Although the true incidence of spinal dysraphia in patients with the VATER association is unknown, current neuroimaging with spinal ultrasonography in the neonatal periodi2J3 and with magnetic resonance imaging at any age14,15permits a noninvasive diagnostic approach to these cases, which may yield a subpopulation of asymptomatic children with spinal dysraphia. The peculiar developmental aspects of the distal spinal column and cord may explain a higher association of dyraphic states at the lumbosacral level. This may be just part of another anomaly in the spectrum of the VATER association. The pathology of the spinal structures in this series is indicative of a primary mesodermal disorder of closure, which then involves the neuroectoderm to varying degrees. No dysplastic or malignant features were noted in any of the excised material. The excised elements were composed of mature cellular elements in an ectopic location or in excess. This was clearly demonstrated by the lipomas. A small amount of fat may be found in the histological analysis of normal filum terminale. However, an excess of fat, recognized as a “thickening” of the filum (of more than 3.0 mm in width) and the extension and “invasion” of the conus by the adipose tissue, is pathological. These histological changes are common to other lipomatous tumors of the conus.’ In spinal hamartomas, fat may be present, but it is always accompanied by other derivatives of the three primary layers and, not uncommonly, the fat is fetal, not mature (adult).16 Whether these histological findings reflect true neoplastic extension, or are simply an additional manifestation of disordered development, remains speculative. ACKNOWLEDGMENT
Fig 2. Section of the filum terminale of another patient, with disorganization and septations within the exhuberant fat. There is no mitotic activity. Dark staining of nerve filaments is seen.
The work.
authors
thank
Julie
Damschen
for excellent
secretarial
REFERENCES 1. James CCM, Lassman LP: Spinal dysraphism. Arch Dis Child 35315327,196O 2. James HE, Walsh JW: Spinal dysraphism. Curr Probl Pediatr ll:l-25, 1981 3. Lichenstein BW: Spinal dyraphism. Arch Neurol Psychiatr 44:792-809, 1940
4. Till K: Spinal dysraphism: A study of congenital malformations of the lower back. J Bone Joint Surg [Br] 51:415-422, 1969 5. Say B, Gerald PS: A new polydactyl, imperforate anus, vertebral anomalies syndrome. Lancet 2:688,1968 6. Say D, Balci S, Pirnay T, et al: A new syndrome of dysmorphogenesis-Imperforate anus associated with poly-oligodactyly and
SPINAL PATHOLOGY
AND VATER ASSOCIATION
skeletal (mainly vertebral) anomalies. Acta Paediatr Stand 60:197202,197l 7. Quan L, Smith DW: The VATER association, vertebral defects, anal atresia. T-E fistula with esophageal atresia, radial and renal dysplagia: A spectrum of associated defects. J Pediatr 82:104-106, 1973 8. Rintala R. Lindahl H, Louhima: VATER association and anorectal malformations. Z Kinderchir 41:22-26, 1986 9. Chesnut R, James HE, Jones KL: The VATER association and spinal dysraphia. Pediatr Neurosurg 18:144-148, 1992 10. Barry JE. Auldist AW: The VATER association: One end of the spectrum of anomalies. Am J Dis Child 128:76Y-771. 1974 Il. Lawhon SM. MacEwen GD, Bunnel WP: Orthopaedic aspects of the VATER association. J Bone Joint Surg [Br] 68:424-429. 19X6
1503
12. James HE, Scheible W. Kerber C, et al: Comparison of high resolution real time ultrasonography and high resolution computed tomography in an infant with dyraphism. Neurosurgery 13:301-305, 1983 13. Scheible W, James HE, Leopold CR, et al: Occult spinal dysraphism in infants: Screening with high resolution real-time ultrasound. Radiology 146:743-746, 1983 14. Hamgan WC, Wright SM. Wright RM: Clinical utility of magnetic resonance imaging in pediatric neurosurgical patients. J Pediatr 108522-529, 1986 15. Altman NR, Altman DH: MR imaging of spinal dysraphism. AJNR 8533-538. 1987 16. Tibbs PA, James HE, Rorke LB, et al: Midline hamartomas masquerading as meningomyeloceles or teratomas in the newborn infant. J Pediatr 89:928-933. 1976