Dewlap. Med. Child Neural. 1973, 15, 194-199

Case Report

Cervical Cord Compression in Mucopolysaccharidosis

Philip Kennedy* Michael Swash* M . F. Dean?

Introduction Gait disorders are a well-known clinical

feature of the mucopolysacharidoses (MC- Kusick 1966). They are commonly due to a primary bone disorder which may either be present at birth as a talipes deformity or may develop later as a syndrome re- sembling Perthes disease. The range of orthopaedic deformity is wide (Einhorn et al. 1946); it may be very severc or limited simply to slight stiffness of joint movement.

Gait disorder in these diseases may also be duc to hydrocephalus. This is particu- larly common in Hurler's syndrome in which thickening of the meninges may cause communicating hydrocephalus (Mc- Kusick et al. 1965, Benson et al. 1972). Compression of the spinal cord in the thoraco-lumbar region has also been described in this condition (Gardner 1965, McKusick 1966).

This paper describcs two siblings affected by a clinically and biochemically distinct variant of mucopolysaccharidosis. One of them presented with a spastic paraparesis which was found to be due to compression of the spinal cord in the high cervical region.

* Section of Neurological Sciences, The London

t The Mathilda and Terence Kennedy Institute

Reprint requests to Dr. Michael Swash, The

Hospital, London El IBB.

of Rheumatology, London W.6.

London Hospital, London El IBB.

Case Reports CASE 1

A 16-year old girl was admitted for investigation of progressive difficulty in walking. For three months she had been aware of stiffness affecting both legs and this had gradually become more severe until it interfered with her daily life. There were no sensory symptoms and micturition was normal.

On examination the patient was an inteliigent young woman with abnormal facies, prominent maxillae and a depressed broad nose, but there was no hypertelorism. Both corneae were clouded. The hair was coarse and dark and the hair-line was low. The external ears were normally developed. The head circumference was 59cm. There was moderate dwarfism, with a prominent lumbar lordosis. Crown-to-ground height was 140cm and pubis-to- ground height was 74cm. The neck was short but all spinal movements were full. Shoulder abduction was limited to 80" on both sides. At the hips, flexion, internal and external rotation were also limited. There was some local pain at the extremes of movement of these joints. The hands showed a claw deformity, with incurving of the little fingers, moderate fixed flexion of the interphalangeal and metacarpophalangeal joints, and bulbous, poorly developed terminal phalanges. In the cardio- vascular system there was a moderately loud ejection murmur at the apex which radiated to the base, and an early, soft, diastolic murmur was audible a t the left parasternal edge. The blood pressure was 100/60. There was no cardiac failure. The thorax was of normal shape. The liver and spleen were not enlarged.

There was a moderately severe spastic para- paresis. Weakness predominantly affected hip flexion and dorsiflexion of the feet, and there was marked spasticity, particularly in the adductors. The tendon reflexes in the legs were abnormally

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CASE REPORT

brisk, with sustained clonus both at knees and ankles and the abdominal reflexes were absent. Both plantar responses were extensor. There was no spasticity or weakness in the arms, but the tendon reflexes were very brisk. The jaw ierk was normal. Sensory examination was normal and no abnormality was found in the cranial nerves or fundi. There was no deafness. There was no cerebel!ar ataxia.

The total amount of uronic acid excreted in a 24-hour urine collection (a measure of total glycosaminoglycan excretion) was 23mg, and the percentage composition of glycosaminoglycans isolated from this sample was dermatan sulphate 62.8 per cent, chondroitin sulphate 35.7 per cent and heparan sulphate 2.2 per cent (see Dean et 01. 1971).

X-rays of the pelvis revealed dysplasia of the acetabnlae and there was a bilateral coxa vara deformity. In the hands there was delayed fusion of the distal metacarpal epiphyses. The carpal bones were hypoplastic and there was faulty

modelling of the distal ends of the radius and ulna. Skull x-rays showed a j-shaped sella. Tomography of the foramen magnum showed that the maximum bony diameter of the spinal canal at this level was 25mm in the sagittal plane. There was no basilar invagination. The odontoid process was normally formcd and there was no atlanto-axial subluxation. However, there was a slight cervical kyphosis. The cervical vertebrae themselves were dysplastic (Fig. 1). The abnormality of the vertebral bodies extended throughout the spine. At the L5/S1 level there was a grade 1 spondylolisthesis.

A positive contrast myelogram (Dr. Leon Morris) showed prominent indentations of the column of contrast by the intervertebral discs at all levels. There was a complele block to the flow of contrast at the C5/6 level and the examination was therefore completed by a high, lateral cervical injection of contrast. There was a marked defect in the column of contrast at the level of the odontoid process and the effective sagittal diameter of the spinal canal was reduced throughout the cervical

Fig. 1. Lateral view ofcervical spine. The vertebral bodies are dysplastic, and their anterior margins have a beaked shape. The upper part of the spinal canal is unusually narrow. The sella i s J-shaped. mentous thickening.

Fig. 2. Myelogram. There is marked narrowing of the column of contrast in the upper cervical region, most obvious at the level of C1 and C2. This was found at opzration to be due to liga-

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DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1973, 15

region (Fig. 2). This was most severe at C1, where the effective sagittal diameter of the spinal canal was only 6nim. It was concluded that there was severe canal stenosis which was due both to ligamentous hyperplasia and to stenosis of the bony canal itself. On the following day a cervical laminectomy was performed (Prof. E. S. Watkins).

The laminectomy included the lamina of C2 and the posterior arch of the atlas and extended downward as far as the lamina of C5. All the laminae were flat and aligned horizontally, and the spinous processes were poorly deve!oped. In the operating position, the posterior arch of the atlas was found to lie within the posterior margin of the foramen magnum. Part of this posterior margin was therefore excised to facilitate access to the arch of the atlas and the dura was opened from C1 to C6. The cord was found to be tightly compressed by thickened dura at the Cl-C2 level. This thickened dural tissue was excised; histological examination showed that it consisted of cartilage, fibro- cartilage and mature collagen.

Post-operatively there was an immediate and thenaslow, continuedimprovement in thepatients’ gait. Her post-operative course was complicated by a cerebrospinal fluid leak from the laminectomy incision but this closed spontaneously. Several weeks later a collection of fluid appeared at this site. This pseudonieningocoele enlarged and became tense and, when repeated lumbar punc- tures did not reduce its size, a ventriculo-atrial shunt was inserted. It then gradually became smaller.

Four months after the laminectomy her walking was almost normal, although there was still some spasticity in the legs and both plantar responses were extensor.

CASE 2 The 21-year-old sister of Case 1 had bilateral

talipes deformities at birth which were treated with elastic strapping during the first year of life. At the age of seven years the deformities described in her sister wereobservedandat 14 years she was treated for delayed puberty with a course of ethinyl oestradiol. At 16 years of age, because of fixed flexion deformity of the hips, which interfered with her gait, she had a left femoral intertrochanteric osteotomy, and a similar procedure was carried out on the right side the following year. After these procedures her gait improved and when she was examined during her sister‘s illness her only com- plaints were of exertional dyspnoea, irregular menses, and inability to abduct her arms fully.

On examination she was alert and intelligent. The same general physical deformities were noted

as in her sister; the facial features, in particular, were strikingly similar. Crown-to-ground height was 131cm, and pubis-to-ground height was 68cm; her head circumference was 56cm. No abnormalities were found in the nervous system and the liver and spleen were not enlarged. An ejection murmur was audible at the cardiac apex and at the base. The total 24-hour urinary excre- tion of uronic acid was 15.9mg, the constituent glycosaminoglycans being dermatan sulphate 87 per cent, chondroitin sulphate 8‘7 per cent and heparan sulphate 4 .3 per cent. A peripheral blood film showed cytoplasmic inclusion granules in polymorphonuclear leucocytes, typical of Alder’s anomaly. X-rays of the skull showed a J-shaped sella turcica. Tomograms of the foramen magnum were normal. The body of the eleventh thoracic vertebra was dysplastic and the posterior surfaces of the lumbar vertebae were scalloped. The ribs were spatulate. The acetabulae were dysplastic and there was bilateral coxa vara deformity. The acromio-clavicular joints were abnormally wide. There were epiphyseal abnormalities at the upper ends of both humeri, fragmentation of the epiphy- ses at the femoral heads, and delayed fusion of the distal metacarpal epiphyses. The distal ends of the radius and ulna were normal.

Discussion Although it was clear that these two

siblings were suffering from a mucopoly- saccharidosis, the clinical and laboratory features were unusual and differed from those usually found in any one of the recognised varieties of mucopolysacchari- dosis (Maroteaux and Lamy 1965, Mc- Kusick et al. 1965, McKusick 1966).

McKusick et al. (1972) have recently reviewed the problem of ‘intermediate phenotypes’. They have suggested that an intermediate phenotype may occur: (a) when there is heterozygosity of alleles at the locus of one of the clearly defined types of mucopolysaccharidosis; (b) when a genetic compound of the genes of one of the recognised disorders and of another unidentified allele occurs at the same locus; or (c) when there is homozygosity at a locus other than that of the classical disorder which it most closely resembles. Without fibroblast culture and studies of

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CASE REPORT

the effect of correcting factors it is not possible to draw firm conclusions con- cerning classification of our two cases. However, the clinical and biochemical features resemble those of Case 5 in the report of McKusick et al. (1972). McKusick and his colleagues regarded this patient as a genetic compound of the Hurler and the Scheie syodromes.

In our cases, the total excretion of polymeric uronic acid was several times greater than the normal level of 2 to 5mg per 24 hours found in mature females (Di Ferrante et al. 1972). This increase was largely attributable to dermatan sulphate, which accounted for almost 63 per cent of the total glycosaminoglycans excreted in Case 1 and for 87 per cent in Case 2. The bulk of the remaining glycosaminoglycans consisted of chondroitin sulphate, with heparan sulphate amounting to less than 5 per cent of the total in each case. Such high levels of dermatan sulphate excretion, with correspondingly low excretion of heparan sulphate, are typical of mucopoly- saccharidoses types V or VI in the classifi- cation of McKusick (1966), although the total glycosaminoglycan excretion was considerably lower than in previously reported cases of either Scheie or Maro- teaux-Lamy syndromes (McKusick 1966).

Spinal cord compression is an unusual manifestation of mucopolysaccharidosis. It almost invariably occurs in the low thoracic region, at the level of a gibbus (see Fig. 128 in Gardner, 1965) and is much commoner in the Hurler and Morquio syndromes than in other subgroups of the disease (Maroteaux and Lamy 1965, Mc- Kusick et al. 1965).

In our Case 1, however, spinal cord compression was due to an abnormality in the cervical region which consisted both of stenosis of the cervical bony canal itself, and of ligamentous thickening. These two abnormalities markedly narrowed the effective lumen of the spinal canal through-

out the whole cervical region. The impor- tance of a narrow cervical spinal canal in the pathogenesis of the myelopathy which is sometimes associated with cervical spondylosis is well-established (Nurick 1972) and in these cases of cervical spondy- losis, as in our case of mucopolysacchari- dosis, the myelographic abnormality is most marked at the intervertebral discs. In our patient the myelographic abnormality was due to true ligamentous thickening, the result of deposition of mucopoly- saccharides and of abnormalities in the structure of the collagen. There were no degenerative or spondylotic changes. Liga- mentous thickening is a well-recognised feature of the Hurler syndrome in which these and other tissues contain clear cells, thought to be derived from fibroblasts (McKusick et al. 1965; McKusick 1966). The collagen fibres in these cases are swollen and homogenous, lacking their usual fibrillary characteristics.

There have been no previous descrip- tions of cervical myelopathy due to ligamentous thickening associated with mucopolysaccharidosis. Gilles and Devel (1971) described a boy with Morquio’s syndrome who became quadriplegic after a fall at the age of three years. He was found to have an unstable cervical spine due to a congenital malformation at the foramen magnum, which consisted of assimilation of the arch of the atlas into the occiput, an abnormal odontoid and a posterior dislocation of the body of the third cervical vertebra. At autopsy, liga- mentous hypertrophy was not remarked upon. Einhorn et al. (1946) described a similar case of mucopolysaccharidosis with a complex congenital anomaly of the cervical spine. In our case the gait disorder was slowly progressive. It was not associa- ted with trauma to the cervical spine and there was no complex congenital anomaly at the foramen magnum. Although the bony cervical canal was congenitally

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DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1973, 15

narrow, the spinal cord compression was shown at operation to be due to thickening of the dural sheath and not to stenosis of the bony canal alone.

Spastic paraparesis in the Hurler syn- drome is commonly due to hydrocephalus (McKusick 1966). Although pneumo- encephalography was not performed in our case, the clinical features of the gait disorder were unlike those described in patients with hydrocephalus (Yakovlev 1947, Hagberg and Sjorgen 1966). The head was not enlarged, and the gait disorder improved after cervical laminec- tomy. The ventriculoatrial shunt, which was inserted several weeks post-operatively for the relief of a pseudomeningocoele, did not modify the clinical course of the recovery from spastic paraparesis.

Our case is important, therefore, in that it demonstrates that spastic paraparesis occuring in a patient with mucopoly- saccharidosis may be due to compression of the cervical spinal cord, the result of ligamentous thickening rather than of cervical osteodystrophy. This possibility should always be excluded in such cases since surgical decompression is likely to be very effective.

Finally, not all gait disorders in muco- polysaccharidosis are due to neurological complications of the disease. In Case 2, the sister of Case 1, impairment of gait was due to bilateral epiphyseal dysplasia of the femoral heads.

Acknowledgement: The patient was under the care of Dr. A. Ridley and we thank him for allowing us to make this report.

SUMMARY Two sisters are described who were suffering from an unusual and clinically distinct

variant of mucopolysaccharidosis. One sister presented with a slowly progressing parapare- sis which was found to be caused by compression of the cervical spinal cord by ligamentous thickening, in association with stenosis of the bony spinal canal. There was rapid and almost complete recovery after decompressive laminectomy. The importance of this finding is discussed in relation to the occurrence of gait disorders in the mucopolysaccharidoses. It is suggested that these two sisters may tepresent a genetic compound of the Hunter and Scheie syndromes.

RBSUMG Compression de la moelle cervicale et mucopolysachcaridose

Les auteurs ont observt deux soeurs souffrant d’une forme inhabituelle et cliniquement distincte de mucopolysaccharidose. L’une des soeurs a prtsentt une parapartsie lentement progressive dont la cause s’est rtvelte Ctre une compression de la moelle cervicale par tpaississement ligamentaire associt a une sttnose du canal rachidien. I1 y eut rtcuptration rapide et presque complkte ap rb laminectomie dtcompressive. L’importance de cette observation est discutte en relation avec la frtquence des troubles de la dtmarche dans les mucopolysaccharidoses. II est suggtrt que ces deux soeurs pouvaient prksenter une com- binaison gtnttique des syndromes de Hunter et de Scheie.

ZUSAMMENFASSUNG Halsmarkkompression bei Mukopolysaccharidose

Es werden zwei Schwestern beschrieben, die eine ungewohnliche klinisch eindeutige Form der Mukopolysaccharidose hatten. Eine Schwester hatte eine langsam fortschreitende

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CASE REPORT

Paraparese bedingt durch die durch ligamentare Verdickungen und Stenose des knochernen Spinalkanals hervorgerufene Kompression des Halsmarks. Nach Dekompression durch Laminektomie trat eine schnelle und fast vollstandige Heilung ein. Dieser Befund wird im Zusammenhang mit Gangschwierigkeiten bei Mukopolysaccharidosen diskutiert. Es wird angenommen, da (3 diese beiden Schwestern eine genetische Mischform des Hunter- und Scheie-Syndroms aufweisen.

RESUMEN Compresidn de la mkdula cervical en mucopolisacaridosis

Se describen dos hermanas que padecian una variante clinicamente distinta de mucopoli- sacaridosis. Una hermana presentaba una paraparesia lentamente progtesiva que se ha116 que era causada por una compresibn de la mbdula cervical debida a un engrosarniento ligamentoso, junto con estenosis del canal 6seo raquideo. Hubo una recuperaci6n rhpida y casi completa despues de una laminectomia descompresiva. La importancia de este hallazgo se discute en relaci6n con la aparici6n de alteracih en la marcha en las mucopolisacaridosis. Se sugiere que estas dos hermanas pueden representar un componente genCtico de 10s sindromes de Hunter y Scheie.

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