Surgical Correction of a Sacral Meningomyelocele in a Dog

Introduction

Neural tube defects resulting in congenital malformations of the vertebral column and spinal cord have been uncommonly reported in domestic animals. The true incidence of such congenital abnormalities is unknown, but a previous report suggests the incidence of spina bifida in dogs is 0.006% and in cats is 0.09%.¹ Manifestation of neural tube defects such as meningomyelocele may range from a malformation that is never detected to those that are incompatible with life. In domestic animals, neural tube defects are typically not detected until after birth, and most neurologically impaired animals are euthanized due to unacceptable neurologic function. A better understanding of the pathogenesis, prevention, and possible therapeutic interventions of affected animals may result in better outcomes. This case report describes the MRI findings, surgical correction, and proposed pathogenesis of spina bifida and meningomyelocele in a dog.

Case Report

A 15 wk old male German shepherd dog weighing 18 kg was presented to the Neurology service at Red Bank Veterinary Hospital for evaluation of a nonhealing cutaneous lesion on the dorsal midline at the level of the lumbosacral region, urinary incontinence, and a deviated tail. The dog was one of eight puppies in the litter. One puppy from the litter had died of unknown causes.

Physical examination revealed unilateral cryptorchidism and abnormal streaming of the hair at the lumbosacral region surrounding a crusted defect in the skin (Figure 1). Clear fluid, presumed to be cerebrospinal fluid (CSF), was leaking through the skin defect. A depression was noted when palpating caudally from the spinous process of the seventh lumbar vertebra to the sacrum, and the dog’s tail was deviated to the left. On neurologic examination, the dog had an equivocally short-strided gait in both pelvic limbs. Postural reactions and spinal reflexes were normal in all four limbs. Sensation was normal in all cutaneous autonomous zones of the pelvic limbs, penis, prepuce, and perineum. However, right-sided analgesia of the skin at the base of the tail was noted. Additionally, the dog’s perineal reflex and anal tone were normal. Mentation and cranial nerve examination were within normal limits. The dog also episodically dribbled urine, although he would posture and void urine normally as well. The neuroanatomical diagnosis was consistent with a lesion affecting sacrocaudal spinal cord segments, roots, or nerves. A spina bifida was suspected for the sacrum and first few caudal vertebrae.

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A complete blood count revealed anemia (hematocrit was 33.7%; reference range, 37.3–61.7%) and monocytosis (1.25 × 10⁹/L; reference range, 0.16–1.12 × 10⁹/L). Serum biochemical profile revealed hyperchloremia (124 mmol/L; reference range, 105–119 mmol/L), hypoproteinemia (47 g/L; reference range, 48–72 g/L), and hypoglobulinemia (21 g/L; reference range, 23–38 g/L). The blood work abnormalities were attributable to the dog’s age. Routine preanesthetic thoracic radiographs were normal with no apparent abnormalities of the caudal cervical and thoracic vertebrae.

MRI of the lumbar and sacral vertebral column was performed with the dog in dorsal recumbency using a 1.0 Tesla MRI unit^a and a multichannel phased array spine coil. T2-weighted images, T1-weighted images (T1-WI) and T1-WI following intravenous administration of a contrast agent^b (0.1 mmol/kg) were acquired in sagittal, dorsal, and transverse planes. The MRI (Figure 2) revealed an incomplete dorsal lamina of the sacrum and first caudal vertebrae, which was most evident on the transverse images. The subarachnoid space extended through the absent vertebral arch into the epaxial musculature and subcutaneous fat to the overlying skin edge. At its connection with the skin, there was an obvious depression of the skin. There were several linear structures isointense to the spinal cord within the dorsally expanded subarachnoid space, which extended through the caudal vertebrae. Those linear structures were presumed to be spinal nerves coursing through the meningeal structure that extended caudodorsally from the lamina of the sacrum. Subjectively, the meningeal sac and nerves of the cauda equina that remained within the vertebral canal appeared dorsally displaced at the level of the body of the seventh lumbar vertebra and sacrum. Tissue that was hyperintense on T1-WI and T2-weighted images consistent with epidural fat was present in the space vacated by the displaced meningeal sac. The vertebral bodies of the lumbar, sacral, and caudal vertebrae were normal. Additionally, on the transverse images, the lumbosacral trunk and ischiatic nerves appeared normal. Illustrations of the malformation have been provided in Figure 3.

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Based on the dog’s age, clinical signs, and imaging findings, spina bifida with meningomyelocele was diagnosed. Due to the risk of infection through the skin defect, tethered cord syndrome (abnormal tension on spinal cord with growth due to meningeal attachments to skin), and progression of signs with maturity, surgical correction of the meningomyelocele was pursued.^2–4

Prior to surgery, the hair was clipped and aseptically prepared over the dorsum surrounding the skin defect from the fifth lumbar vertebra through the lumbosacral region. An elliptical incision from the sixth lumbar vertebra to the first caudal vertebra around the skin defect was made (Figure 4). The fascia and epaxial muscles were sharply dissected deeply until a tubular structure (meningeal sac) contiguous with the skin defect was identified. The dissection was continued around the meningeal sac that continued from the skin defect and extended cranially through the bifid arches of the first caudal vertebrae and sacrum. The meningeal sac was opened at the most caudal aspect of the dissection with iris scissors and 4-0 polydioxanone^c stay sutures were placed in the caudal and cranial portion of the opened sac. The abnormal skin was sharply dissected away from the dura of the sac and transected from its abnormal neural attachments. Through the open meningeal sac, the conus medullaris, filum terminale, and remaining normal sacral nerve roots were identified. The open sac was then sutured closed with 4-0 polydioxanone in a simple continuous pattern. A hemostatic sponge^d was placed over the closed dura. Standard closure of the epaxial muscles, subcutaneous tissue, subcuticular layer, and skin were performed. Postoperatively, the dog was treated with cephalexin^e (28.2 mg/kg per os [PO] q 12 hr), tramadol^f (1.4 mg/kg PO q 8 hr as needed), gabapentin^g (5.6 mg/kg PO q 24 hr), famotidine^h (0.6 mg/kg PO q 24 hr), and prednisoneⁱ (0.6 mg/kg PO q 12 hr), which was gradually tapered over 3 wk.

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Two weeks postoperatively, the incision was healed and the owners reported decreased incidence of urinary incontinence. Physical and neurologic examinations were otherwise unchanged from prior to surgery. Four months postoperatively, the owners reported via telephone only rare incidences of urine dribbling, a tail that was no longer deviated, and no evidence of pain or discomfort at the previous surgical site.

Histopathology of the skin defect and associated tubular structure revealed a segment of spinal cord parenchyma that contained remnants of the central canal lined by cuboidal to columnar cells that resembled ependymal cells. This parenchyma was surrounded by a thin layer of fibrous tissue resembling meninges. Within the spinal cord parenchyma were multiple small capillaries, glial cells, and occasional neurons. This confirmed the presence of a meningomyelocele (Figure 5).

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Discussion

Congenital malformations of the vertebral column and spinal cord arise secondary to errors during neurulation or neural tube development. During normal primary neurulation, the surface ectoderm thickens, leading to the formation of the neuroectodermal neural plate. The neural folds then develop laterally from the neural plate, creating a central neural groove and eventually fuse dorsally following separation from the overlying ectoderm.^5,6 Neural tube closure by fusion of the neural folds is initiated at either the rostral rhombencephalon or mesencephalon depending on the species.^5,6 It has been shown that there may be at least 3–5 closure initiation sites in humans and other animals, including mice, rats, hamsters, chicks, and rabbits (Figure 6).^7–10 The rostral neuropore is closed first while the caudal neuropore is closed last at the end of primary neurulation. The development of the neural tube in the lumbosacral region occurs through a process called secondary neurulation or cavitation. In this region, a solid cord of neuroepithelial cells migrates caudally from the neural tube on the midline ventral to the surface ectoderm. The central canal is formed by cavitation of this column of cells, which is continuous with the central lumen of the neural tube cranially.^5–7 Just lateral to the developing neural tube is the paraxial mesoderm, which becomes segmented into somites. The somites develop subdivisions including the dermatome, myotome, and sclerotome. The dermatome eventually contributes to the development of the dermis deep to the surface ectoderm, the myotome to the axial and appendicular muscles, and the sclerotome to the vertebrae and ribs. The notochord is ventral to the neural tube and provides growth factors for the development of the neural tube and paraxial mesoderm. The notochord becomes retained as the nucleus pulposus of the intervertebral discs.⁵

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Neural tube defects may occur anywhere along the formation of the central nervous system from the brain to the caudal spinal cord segments.⁸ However, defects in the lumbosacral region of the spinal cord have been reported more commonly, possibly related to later development of the caudal neuropore during neurulation.⁷ Terminology used to describe specific types of neural tube defects can be confusing as more than one defect may be present in a single animal. Myelodysplasia refers to any malformation of the spinal cord that can arise due to abnormal interaction of the notochord, paraxial mesoderm and neural plate during neurulation.⁵ Spinal dysraphism refers to the failure of neural folds to appose and close to form the neural tube, but that term has been largely replaced by the term myelodysplasia in the literature.^5,11 The terminology is further confused by the fact that a specific disease mainly of Weimeraners has been described as spinal cord dysraphism, which is now considered to be a misnomer. In dogs with this form of myelodysplasia, there is normal closure of the neural tube but there may be several abnormalities within the spinal cord, including hydromyelia, syringomyelia, syringohydromyelia, spinal cord duplication, and anomalies in the dorsal and ventral gray matter.¹¹ Such anomalies may arise from the abnormal migration of mantle cells following neural tube closure but not due to failure of the neural tube to form, as the name would suggest.^5,11–13 Myeloschisis describes the failure of neural tube closure in which the skin ectoderm remains attached to the edges of the neural plate, preventing proper development of the vertebral arches over the open neural plate.⁶ Myeloschisis requires an accompanying spina bifida or rachischisis. Dermoid sinus is a neural tube defect most commonly reported in Rhodesian ridgebacks that arises due to abnormal separation of the neural tube from the skin ectoderm during embryogenesis.¹⁴ Spina bifida is the condition in which one or a few of the vertebral arches fail to close over the spinal cord. It may occur with no abnormality of the neural tube (spina bifida occulta) and, therefore, no accompanying neurologic signs. Spina bifida may also occur with other defects such as a meningocele (a protrusion of meninges through an open vertebral arch) or more commonly meningomyelocele (a protrusion of meninges and nervous tissue through an open vertebral arch) as in this case report. It is common for the spinal cord within and adjacent to a meningomyelocele to show additional myelodysplasia.⁵ Spina bifida has been reported in many domestic animals including dogs, cats, and cattle.^{1,3,4,15–26} The etiology of neural tube defects is suspected to be multifactorial dependent on gene-gene, gene-nutrient, and gene-environment interactions.⁹ In humans, many factors have been associated with neural tube defects, including chromosomal and single gene disorders, twinning, consanguinity, geographic areas, socioeconomic status, seasonal variations, ambient exposure to airborne chemicals, hyperthermia, and maternal nutrition (folate, vitamin B₁₂, homocysteine, zinc, etc.).^7–9

The dog reported herein was diagnosed with spina bifida with meningomyelocele. The vast majority of neural tube defects occurring in the lumbar region are due to errors of primary neurulation, but errors in secondary neurulation have also been suggested.⁵ To determine whether the defect in the patient described herein arose from errors during primary versus secondary neurulation requires the determination of the exact location of the closure of the caudal neuropore in dogs. A defect occurring at a site caudal to the site of caudal neuropore closure would suggest a defect in secondary neurulation. Although speculative, the defect described in this report was likely the result of an error in secondary neurulation as the lesion occurred at the sacral and caudal vertebrae. Additionally, there likely was an aberrant attachment of the proliferating column of neuroepithelial cells to the overlying skin ectoderm at the caudal end of the column of cells. When the meninges formed around this developing neural tube, the subarachnoid space extended to the skin surface at the site of this aberrant attachment. At some point, as the vertebral column outgrew the spinal cord and its nerves, the subarachnoid space communicated with the skin surface. The spina bifida developed when the sclerotomal mesoderm that forms the vertebral arches was unable to develop at the site of this aberrant attachment. Alternatively, a persistently open caudal neuropore leading to subsequent errors in secondary neurulation yielding a bifid caudal neural tube has also been suggested.²⁷ Other possible explanations include hyperplasia of the neural tube cells preventing neural tube fusion, rupture of a previously closed neural tube, and vascular defects to the dorsal aspect of the spinal cord.^1,18,19,22 This case is also unique in that there was direct communication of the subarachnoid space and the environment. On physical examination, CSF was found leaking through the skin defect and that communication was confirmed on the MRI. It was previously suggested that necrosis at a single point of the meningocele and overlying skin may allow fluid to escape to the skin surface.²⁴ The study authors suggest that erosion at the point of attachment from the surface ectoderm to the neural tube, and splitting of the dura and arachnoid layers allowed for CSF leakage onto the skin surface to occur.

Three reports of surgical therapy of neural tube defects in dogs, including two with favorable outcomes, have been previously reported.^3,4,28 In the present case, surgical intervention was undertaken in an effort to prevent infection in the subarachnoid space. Although unknown, bacterial contamination of the subarachnoid space resulting in meningomyelitis would have likely occurred over time. Consequently, the main goal of surgery was to close the skin defect and resect the connection between the subarachnoid space and external environment. To that end, surgery was successful. Moreover, surgical intervention was also pursued in an effort to prevent neurologic deterioration secondary to tethering of the neural structures as the dog matured. Four months postoperatively, at 8 mo of age, the dog had not developed any other neurologic signs and had improvement of its initial deficits, mainly dribbling of urine. However, longer follow-up time is necessary to determine long-term success of the surgery.

In both humans and animals, various other congenital abnormalities have been associated with spina bifida. In animals, hydrocephalus, displacement of the cerebellum, myelodysplasia of adjacent spinal cord, arthrogryposis, and other vertebral abnormalities (such as block or hemivertebra) have been reported.^{1,5,19,21,21,25,26} Such previously reported anomalies were not detected in the patient reported herein by the diagnostics performed.

In humans, spina bifida has been associated with cryptorchidism.²⁹ It is unclear whether the cryptorchidism present in the patient reported herein is related to its spina bifida. Important structures involved in testicular descent include the testis, epididymal and deferent ducts, cranial suspensory ligament of the testis, gubernaculum, cremaster muscle, genitofemoral sensory nerve, and the first and second lumbar ganglia containing the spinal nucleus of the genitofemoral nerve.^30,31 During the inguinoscrotal migration of the testis, testosterone binds to androgen receptors present in the genitofemoral nerve cell body and stimulates release of calcitonin gene-related peptide from the genitofemoral nerve.³⁰ Calcitonin gene-related peptide acts as a chemoattractant and directs the tip of the developing gubernaculum into the scrotum.³⁰ Neuronal anomalies affecting either the genitofemoral nerve or its ganglionic cell bodies could result in cryptorchidism.³¹ Although such pathophysiology related to neural tube defects could explain the findings in the case reported herein, other neurologic deficits attributable to the genitofemoral nerve were not identified. However, a dog presenting with cryptorchidism should suggest that other congenital defects such as a neural tube defect might be present, necessitating a thorough neurologic examination. Due to the possible genetic etiology of cryptorchidism and neural tube defects, prompt castration should be recommended.

Conclusion

To the authors’ knowledge, this is the first case report of spina bifida and meningomyelocele with MRI findings and successful surgical intervention of this congenital defect in a dog. Although the aim of surgical intervention was not to reverse the neurologic deficits, closure of the skin defect and subarachnoid space prevented future bacterial contamination of the subarachnoid space and subsequent meningomyelitis. Future investigations are needed to better understand the prevalence of maldevelopment of neurulation and to determine the long-term outcome in dogs undergoing surgical intervention. Given the possible association between spina bifida and cryptorchidism in dogs, animals presenting with malformations involving the genitalia, should be scrutinized for concurrent congenital disorders such as neural tube defects.