Spinal cord compression in Morquio-Brailsford's disease

April, 1969 T h e Journal of P E D I A T R I C S

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Spinal cord compression in MorquioB ra i l ord 's disease Eight patients with Morquio-Brails[ord's disease have been [ollowed neurologically. All 8 had roentgenographie evidence o[ hypoplasia or complete absence o[ the odontoid and o/ thoracic gibbus [ormation. Four o[ the 8 patients had evidence o[ cervical cord compression secondary to atIantoaxial dislocation or subluxation. Two patients had thoracic cord compression at the level of the gibbus. Prevention o[ spinal cord compression may be possible by the application o[ a Milwaukee brace during early childhood. If serial neurological examination reveals spinal cord damage, surgical intervention is indicated.

Michael E. Blaw, M.D.,* and Leonard O. Langer, M.D. D A L L A S , TEXAS~ AND M I N N E A P O L I S ,

MINN.

MoRQuIO'S D I S E A S E , or MorquioBrailsford's disease (MBD), is a heritable condition with an autosomal recessive mode of transmission. Affected individuals are dwarfed, with the shortening predominantly in the trunk. In recent years it has become clear that MBD represents an inborn error of metabolism in which excessive amounts of keratosulfate, an acid mucopolysaccharide, are excreted in the urine. Subsequent to the initial independent clinical descriptions by Morquio 1 and Brailsford 2 in 1929, considerable confusion has existed as to the exact definition of the condition. Recent studies by Maroteaux, Lamy, and Foucher ~ and by Langer and From the University o/ Texas, Southwestern Medical School at Dallas, Department o[ Pediatrics and Neurology, and the University o[ Minnesota Medical School, Department of Radiology. ~Address: Department o[ Pediatrics and Neurology, Southwestern Medical School at Dallas, Dallas, Texas 75235.

Carey 4 have clearly defined MBD and demonstrated that specific bony involvement, resulting in characteristic roentgenographic features, is found in patients who excrete excessive amounts of keratosulfate. The purpose of this report is to point out that serious complications may be associated with the bony deformity in the vertebral column. Spinal cord compression in the upper cervical segments develops from atlantoaxial dislocation or subluxation, or at the level of the thoracolumbar gibbus. These complications may be preventable by prophylactic bracing.

MATERIAL AND METHODS The patients included in this study have all been examined at the University of Minnesota Hospitals. The diagnosis of MBD has been established by the presence of the characteristic clinical and roentgenological features outlined as follows. Increased amounts of urinary keratosulfate were demVol. 74, No. 4, pp. 593-600

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onstrated in these patients (Dr. Alfred Linker of Salt Lake City, U t a h ) . CLINICAL FEATURES 1. Fine corneal opacities frequently demonstrable only on slit lamp examination. 2. Thin enamel layer of both the deciduous and permanent teeth which gives a greyish-yellow cast to the teeth on inspection. Dental roentgenographs demonstrate this feature conclusively. The thin enamel predisposes to dental caries. 4 3. Impairment of hearing is common and frequently appears to have both a conductive and a neurosensory component. 4. Ligamentous relaxation is present in the joints of the extremities, particularly in the peripheral ones. Flat feet and genu valgum develop secondary to this and to the bony deformity. 5. Motion at the hips is frequently restricted; this becomes more marked with

increasing age, paralleling the progressive bony deformity in this region. 6. Deformity of the vertebral column is profound and progressive through the period of growth, with the development of kyphosis and pectus carinatum (Fig. 1). 7. In older childhood a typical facial configuration evolves, as pointed out by Maroteaux and associates? Usually children with this condition are not considered to be abnormal by their parents until the second or third year of life. ROENTGENOGRAPHIC

FEATURES

(Figs. 2 and 3). In this condition there is a typical evolution of osseous changes with increasing age. This has been described and illustrated by Langer and Carey. 4 At the age when the child with MBD is referred to the physician, usually about 2 years, all of the vertebral bodies are flatter than normal. Hence, universal platyspon-

Fig. 1. Five-year-old boy with Morquio-Brailsford's disease.

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dyly is a diagnostic sine qua non. The shape of the vertebral deformity differs in the lumbar and thoracic vertebrae; this pattern differentiates MBD from other conditions with universal platyspondyly. In the lumbar and thoracolumbar junction regions the bodies have a defect in their anterosuperior aspect. Commonly, relative displacement of adjacent vertebrae develops at the thoracolumbar junction, resulting in formation of a gibbus. In the thoracic region the bodies have an oval shape with a central tongue of bone extending anteriorly. In the cervical region the odontoid process of the axis is hypoplastic or absent. Roentgenographs in flexion and extension show increased mobility at the atlantoaxial junction in childhood. The pelvis is long, with some flaring of the iliac wings and deficient ossification of the superior aspects of the acetabula. Other roentgenographic findings may also be present. Coxa valga of varying severity

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may occur, but coxa vara is not seen. The second to fifth metacarpals have conical bases, with relatively normal constriction of the shafts. There may be some deformity of the distal end of the ulna, with the plane of the growth plate inclined toward the radius. Later, obliquity of the distal end of the radius develops. URINARY. MUCOPOLYSACCHARIDES

Keratosulfate can be demonstrated in small amounts in the urine of normal individuals by refined biochemical techniques. 5 It is not found in normal individuals with the techniques usually employed in clinical laboratories. In children with MBD, relatively large amounts of keratosulfate are present in the urine; in adult patients a smaller amount is present. Individuals with MBD also excrete increased mnounts of chondroitin sulfate A and C, acid muco-

Fig. 2, Roentgenographs illustrating characteristic vertebral and pelvic changes in a 5-yearold patient.

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polysaccharides which are present in substantial quantities in the urine of normal people. Small amounts of keratosulfate have been demonstrated in several generalized bone dysplasias which clearly are not MBD?, 6 These entities do not have the clinical and radiographic features outlined above. The diagnostic criteria outlined are based on clinical-radiographic correlation in 32 cases seen personally, or for whom data were sent to the Registry for Bone l)ysplasias at the University of Minnesota, and on 98 cases published in the world literature in which, in our opinion, adequate data were presented to allow a definitive diagnosis. In all of our personal and referred cases from whom adequate urine specimens were obtained, keratosulfate was demonstrated. RESULTS

C

Eight patients with roentgenographically and biochemically confirmed MBD have been examined neurologically (Table I). All 8 patients had evidence of thoracic gibbus formation and hypoplasia or complete absence of the odontoid, in addition to the other, characteristics of MBD. In all 8, atlantoaxial dislocation or subluxation was demonstrated. Four of the 8 patients were preadolescent. Of these 4 children, 3 were still ambulatory and had no signs of spinal cord compression. Two of the ambulatory children (Patients P. L. and K. D.) have been treated prophylactically in Milwaukee braces for a period of 3 years. One of the preadolescent and all 4 of the postadolescent patients were confined to wheelchairs. All five of these patients had evidence on neurological examination of spinal cord involvement. Corticospinal tract

Fig. 3. Roentgenographs of cervical spine. A, B, Child. Note absence of odontoid and relative motion of C1 in respect to C2 in flexion and extension. C, Adult. Note the posterior arch of C1 fitting into the back of the foramen magnum decreasing its effective size.

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T a b l e I. Clinical signs of spinal cord compression in M B D

Patient K.D. R.F. T.M. P.L. T.V. D.V. G.W. R.S.

t

Sex

Age (years)

Corticospinal tract signs

F M M F M M F F

7 9 10 t3 17 21 36 52

0 + 0 0 + + + +

signs of hyperreflexia, spasticity, clonus, and extensor p l a n t a r response were the most prominent. F o u r of these 5 patients had these signs in all 4 extremities, suggesting cervical cord compression. I n o n e patient these signs were limited to the legs. Sensory deficits were generally n o t profound. Evidence of loss of deep sensation was present in all 5 patients, with loss of vibratory sense in the lower extremities being the most prominent. Loss of superficial sensation was found in the 2 oldest patients, who had sensory levels at T~2. Following are 2 case histories which illustrate the clinical courses of spinal cord compression in MBD.

CASE REPORTS Patient R . F.-UH No. 971956. This patient was a 9-year-old boy in whom signs of spinal cord compression were first recognized at age 5. At that time, increased reflexes were demonstrated in both the arms and legs. The plantar response was extensor on the right and unsustained clonus was present bilaterally. No sensory deficit was documented. During the next 2 years he was placed in a Milwaukee brace. At age 7, while riding a tricycle, he was tipped over and fell to the floor; he was wearing his Milwaukee brace at the time. He struck his left shoulder and left occiput. Following a brief period of apnea, it was discovered that he was not moving his arms or legs. Within 2 to 3 hours of the aocident he was able to move his legs, but his arms remained flaccid. Deep tendon reflexes were absent in the upper extremities and hyperactive in the lower extremities. Bilateral ankIe clonus and extensor plantar responses were still present. No definitive sensory level

Deep sensory I Superficial signs sensory signs 0 + 0 0 + + + +

0 0 0 0 0 0 + +

Ambulatory + 0 + + 0 0 0 0

could be demonstrated, but there was decreased sweating below the C4 dermatome. When further improvement did not occur over the next 48 hours, a cervical laminectomy (C~-Ca with a suboccipital craniectomy) was performed. At the time of the operation the spinal cord was found to be tightly compressed and angulated by the arch of the atlas posteriorly and the bodies of C~ and C~ anteriorly. Following the decompression, there was some return of function in aI1 extremities. Comment. This patient had some evidence of cervical cord compression at five years, prior to the application of external bracing. The space available for the cervical cord was severely compromised, as demonstrated by the fact that relatively mild trauma produced such marked symptoms of spinal cord compression. Patient R. S.-UH No. 781191. The patient was a 52-year-old woman. One sister also had MBD. Although the patient had difficulty with gait for most of her life, she began to experience increasing difficulty at age 33, associated with paresthesias in her right foot. In the succeeding 3 years, her walking became more labored. The area of sensory disturbance increased to involve the entire right leg. When examined neurologically at age 36, she was found to have corticospinal tract signs in both legs, more prominent on the right. A sensory deficit was noted on the right to the level of T~. A myelogram demonstrated partial block at T~ (the level of the gibbus). Subsequently, a laminectomy (T~-L) was performed. The cord was found to be compressed at the level of the gibbus. Although the sensory symptoms abated following surgery, the corticospinaI tract signs persisted. Comment. The presence of a sensory level at T~2, coupled with corticospinal tract signs in the lower extremities, suggested compression at the level of the gibbus. This was confirmed by

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A

C

Fig. 4. Myelographic study in adult. A, Upper cervical and foramen magnum regions, lateral horizontal beam projection. Note the small size of the subarachnoid space outlined by contrast media~ The patient is wearing a hearing aid; B, Thoracolumbar region, lateral projection; C, Lumbar region, frontal projection. Note partial block at the level of gibbus. Multiple bulging discs are also seen. myelography and the subsequent surgery. Nevertheless, the persistence of corticospinal tract signs following surgery raises the possibility that there may be compression at the level of the hypoplastic odontoid.

DISCUSSION T h e normal anatomical relationslaip between the atlas gnd the axis allows for a m a x i m u m of mobility, both rotationally and with flexion and extension movements of the head on the neck. Normally, anteroposterior atlantoaxial subluxation is prevented by the odontoid and the transverse ligament. Subluxation and dislocation have been observed in a number of circumstances including trauma, rheumatoid arthritis, and congen-

ital absence of the odontoid. 79 With involvement of either the transverse ligament or the odontoid, dislocation is more apt to occur in flexion, resulting in anterior displacement of the atlas in relationship to the axis. As a consequence, the upper cervical cord will be angulated and compressed posteriorly by the arch of the atlas and anteriorly by the body of the axis. T h e neurological deficit which results from atlantoaxial dislocation is variable and to a large degree depends upon the acuteness of the process. Sudden dislocation, such as occurs with traumatic fracture of the odontoid, m a y result in hematomyelia or complete trans-section of the cord. Chronic dislocation may lead to intermittent or low-

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Fig. 5. Seven-year-old child with Morquio-Brailsford's disease fitted with Milwaukee brace.

grade constant cord compression. It is not uncommon for symptoms of weakness and spasticity to begin in the lower extremities? ~ Neurological deficits related to involvement of the cervical segments below C2 may result from vascular compression at the site of the dislocation, as observed in Patient R. F. High cervical compression with pathological confirmations in a patient with MBD was first reported by Einhorn and associates. 11 The neuropathological changes were considered to be the result of platybasia. It has since been demonstrated that the platybasia is mote apparent than real, in that anterior dislocation of the atlas places the arch of C1 (Fig. 3, C) in the foramen magnum and gives the false impression of invagination of the base. 4 All of our patients with MBD had hypoplasia or complete absence of the odontoid. Five of 8 developed neurological signs secondary to spinal cord

compression. Although the hypoplastic odontoid couId explain all the neurological findings seen in our patients, it is possible that other anatomical abnormalities may well be contributing to the pathogenesis of the spinal cord compression: (1) Laxity of the ligaments is a common finding in MBD. If this laxity affects the transverse ligament, it too may contribute to the dislocation. There is evidence of increased mobility of the atlantoaxial joint in MBD during early childhood. (2) Because of the growth disturbance affecting the vertebrae, the laminae are foreshortened, resulting in a vertebral canal that is decreased in its anteroposterior diameter. This change in shape of the vertebral canal further restricts movement of the cord in the anteroposterior plane and con tributes to the potential for compression. Laxity of the ligaments and decreased anteroposterior diameter of the vertebral

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canal, coupled with the wedging of the lumbar vertebral bodies, undoubtedly play a role in the production of spinal cord compression at the level of the gibbus. However, in that the spinal cord at this level is quite small relative to the vertebral canal, compression is not as likely to occur as it is in the higher cervical area. This may also be a partial explanation for the fact that the 2 patients who had evidence of compression at the level of the gibbus had onset of symptoms during the fourth decade of life, whereas cervical cord signs became evident during the first 2 decades. MyeIographic evidence of cord compression in the cervical and lower thoracic levels is demonstrable in Fig. 4, A, B, and C. T h e results of this study demonstrate that signs of spinal cord compression are a comm o n finding in patients with MBD. Such signs may be present during childhood, but occur with increasing frequency during adolescence and early adulthood. Since the anatomical abnormalities which lead to the cord compression are present throughout life, it is reasonable to think in terms of prophylaxis. Preventive measures are of great importance since most of these patients are capable of living productive lives if they can be kept ambulatory. At the present time Milwaukee braces (Fig. 5) are being used. It is hoped that this external bracing, if instituted during early childhood, will impede the development of the gibbus. T h e neck piece limits flexion of the head on the neck and helps to protect the cervical cord. It is obvious from the case history of Patient R. F. t h a t bracing will not totally protect the cervical cord from superimposed trauma. T h e experience with prophylactic bracing

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in but 2 patients is not extensive enough to draw conclusions concerning effectiveness. I'n our opinion, if signs of cervical cord compression appear in the face of this conservative approach, serious consideration should be given to surgical intervention involving laminectomy of C1 with fusion of the upper cervical spine to the occipital bone. REFERENCES

1. Morquio, L.: Sur une forme de dystrophic osseuse familiale, Bull. Soc. p~diat, de Paris 27: 145, 1929; Arch. de m~d. d'enf. 32: 129, 1929. 2. Brailsford, J. F.: Chondro-osteo-dystrophy: Roentgenographic and clinical features of child with dislocation of vertebrae, Am. J. Surg. 7: 404, 1929. 3. Maroteaux, P., Lamy, M., and Foucher, M.: La maladie de Morquio: t~tude clinique, radiologique et biologique, Presse mild. 71: 2091, 1963. 4. Langer, L. O., and Carey, L. S.: The roentgenographic features of the KS mucopolysaccharidosis of Morquio (Morqulo-Brailsford's disease), Am. J. Roentgenol. 97: 1, 1966. 5. Varadi, D. O., Cifonelli, J. A., and Dorfman, A.: The acid mucopolysaccharides in normal urine, Biochim, et biophys, acta 141: 103, 1967. 6. Linker, A.: Personal communication. 7. Alexander, E., Jr., Forsyth, tI. F., Davis, C, H., Jr,, and Nashold, B. S., Jr.: Dislocation of the atlas on the axis, J. Neurosurg. 15: 353, 1958. 8. Lourie, H., and Stewart, W. A.: Spontaneous atlantoaxial dislocation: A complication of rheumatoid disease, New England J. Med. 265: 677, 1961. 9. Wadia, N. H.: Myelopathy complicating congenital atlantoaxial dislocation, Brain 90: 449, 1967. 10. Dunbar, H. S., and Ray, B. S.: Chronic atlantoaxial dislocation with late manifestations, Surg. Gynec. & Obst. 113: 757, 1961. 11. E~nhorn, N. H., Moore, J. R., and Rowntree, L. G.: Osteochondrodystrophia deformans (Morquio's disease): observations at autopsy in one case, Am. J. Dis. Child. 72" 536, 1949.