Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Neurologic Problems of the Spine in Achondroplasia
Achondroplasia (“without cartilage formation”) is the most common form of dwarfism in humans and is characterized by disproportionately short stature with rhizomelic shortening of the extremities, macrocephaly, midface hypoplasia, and frontal bossing. , This skeletal dysplasia results from defective formation of endochondral bone, and affects approximately 1 in 25,000 births worldwide. Morbidity in achondroplasia results largely from bony compression of the neuraxis and respiratory failure. , This chapter focuses on the main indications for neurosurgical interventions for problems attributed to the spine in achondroplasia, namely, cervicomedullary compression and spinal stenosis.
Thoracolumbar stenosis resulting in spinal compression is the commonest complication of achondroplasia, becoming symptomatic in most patients in their 20s or later. It is, in most cases, the result of congenitally short pedicles and decreased interpedicular distances. Thoracolumbar stenosis can be accelerated in infants who develop progressive thoracolumbar kyphosis if bracing is not undertaken before vertebral wedging develops. Less common problems in infancy include symptomatic airway obstruction and severe cervicomedullary compression secondary to foramen magnum stenosis. The latter can be sometimes accompanied by swallowing difficulties and central apnea.
Most individuals with achondroplasia have normal intelligence. Motor milestones are delayed, partly because of generalized hypotonia and partly because of the mechanical disadvantage imposed by short limbs. Psychological problems arising from short stature include lack of acceptance by peers and a tendency of adults, including parents and teachers, to treat children with achondroplasia appropriately for their height rather than their age. Involvement with other families with children of short stature can improve self-esteem and can assist parents in guiding their achondroplastic children through the difficulties of growing up in a culture that equates stature to status.
Respiratory complications include obstructive sleep apnea secondary to a small upper airway. Many people with achondroplasia snore. Many infants sleep with their necks in a hyperextended position, a position that functionally increases the size of the upper airway, relieving intermittent obstruction. However, the hyperextended neck position may exacerbate neurologic sequelae of a small foramen magnum and cervicomedullary compression. A small thoracic cage may result in restrictive pulmonary disease in infancy, and respiration can be compromised further by aspiration secondary to gastroesophageal reflux, swallowing dysfunction, or both, resulting in recurrent pneumonia.
Reproductive difficulties have not been conclusively documented, but evidence of reduced fertility, frequent fibroid cysts, and early menopause have been reported. Women with achondroplasia must deliver their infants by cesarean section because of cephalopelvic disproportion, and administration of spinal anesthesia is strongly discouraged due to the small size of the canal.
Although life expectancy was formerly thought to be normal for people with achondroplasia, age-specific mortality is increased at all ages, with the highest increase occurring in children. Moreover, cardiovascular cases of death are increased in the adult group (25 to 54 years of age). The increased mortality in childhood is likely related to severe cervicomedullary compression.
As a result of the disease, the patient with achondroplasia is more likely to seek treatment from a neurosurgical service for one of the potentially debilitating problems mentioned earlier and to face the prospect of surgical intervention. Often, presenting symptoms do not have strictly neurosurgical resolution. For that reason, a comprehensive treatment involving a multidisciplinary team of physicians is useful.
Causes and Pathophysiology
Clinical Genetics and Growth Plate Ultrastructures
Achondroplasia is an autosomal dominant disorder; most estimates of its frequency cluster between 1:25,000 and 1:35,000 live births , ; however, the true frequency may be slightly higher. New mutations account for about 80% of children born with achondroplasia. As in many autosomal dominant disorders, a positive correlation exists between advanced paternal age and occurrence of new mutations. Offspring of couples in which both partners are affected by achondroplasia have a 25% chance of inheriting both parental achondroplasia alleles, resulting in homozygous achondroplasia, which is universally fatal within the first year of life. The skeletal features of achondroplasia are highly exaggerated in the homozygous condition, resulting in significantly shorter limbs, a smaller chest size, and a smaller foramen magnum. Death is usually secondary to respiratory complications, sometimes in concordance with foramen magnum stenosis and brainstem compression.
Achondroplasia results from impaired formation of endochondral bone. A missense mutation, G380R, in the transmembrane domain of fibroblast growth factor receptor 3 has been traced to chromosome 4, at 4p16.3. , The protein is a tyrosine kinase receptor expressed in developing bones. The G380R mutation has been found in most patients. , Several groups used this discovery to develop polymerase chain reaction diagnostic tests. The histochemical features of the endochondral growth plates of achondroplastic bone have been interpreted in several ways. Some researchers suggested that mitotic abnormalities indicate cessation of normal cell function and arrest of cell division of the chondrocytes. This impaired formation of bone from cartilage is seen in the growth of the diaphyses of long bones. In addition, an enlargement of the epiphyses occurs. Cartilaginous synchondroses in the spine and skull seem to fuse prematurely, and hypertrophy of the spinal articular surface occurs. Cervicomedullary compression is typically a pediatric concern, while spinal stenosis is usually seen in adults.
Cervicomedullary Compression
Cervicomedullary compression stems primarily from a reduction in the diameter of the foramen magnum in the sagittal and coronal dimensions that is sometimes more than five standard deviations less than normal. The cranial base (chondrocranium) derives from endochondral ossification. In achondroplasia, the base is stunted, shorter, and narrower that normal. The basioccipital bone, which forms the anterior border of the foramen magnum, is narrow and angulated. The lateral and posterior parts, consisting of the exoccipitalis bone, are similarly deformed, resulting in the diamond, triangular, or teardrop shape of the achondroplastic foramen magnum. In addition, the articular surfaces of the occipital bone (between the lateral occipital and the basioccipital bones and between the lateral bones and the planum nuchale of the squama) are hypertrophic and can encroach on the neural elements within the foramen. The pathology of the achondroplastic skull is further complicated by the small size of the posterior fossa, resulting from stunting of the endochondrally derived planum nuchale, and the resultant horizontalization of the squamous portions of the occipital bones. This constricted arrangement of the skull base displaces the brainstem upward and the foramen magnum anteriorly, resulting in posterior tilting to the brainstem and further impingement of the neuraxis posteriorly ( Fig. 169.1 ).
Thoracolumbar Kyphosis
Kyphosis is prevalent in up to 94% of achondroplastic children under the age of 1 (PMID 9591973 ). It is hypothesized that this deformity is the result of a disproportionately large head and “lax ligaments with unusual vertical load on the anterior column of the spine.” (PMID 28005181 ). When patients get older, walking and skeletal maturation oftentimes exacerbates the kyphosis, and patients develop a compensatory hyperlordosis in the lumbar region, increase in pelvic tilt, and a fixed flexion deformity of the hip (PMID 5479457 ). Nevertheless, not all cases of kyphosis in children progress, and in fact the rate of progression to the point of causing significant cord or cauda equina compression is only 11% (PMID 3240259 ).
Spinal Stenosis
The anatomy of the achondroplastic spine is distinctive in several respects, all of which can contribute to compromise of the spinal cord or nerve roots. , The hypertrophy of epiphyseal articular processes in the long bones is mirrored at the caudal and cephalic surfaces of the vertebral bodies, resulting in a mushroom shape at each end and concomitant scalloping along the posterior surface that is appreciable in a contrast myelogram. Abbreviated and thickened pedicles of the vertebral arches result from premature fusion of synchondroses between the laminae and the vertebral bodies ; the laminae are also thickened. Intervertebral discs tend to bulge prominently, further aggravating neural encroachment by the enlarged vertebral body articular surfaces. The interpediculate distance decreases in the lumbar region of the spine, resulting in a canal that tapers caudally, the opposite of normal (the canal normally widens caudally). The overall picture is one of dramatic stenosis in every dimension of the spine, a stenosis sometimes aggravated by osteoarthritic changes and disc ruptures. Consequently, a generalized constriction of spinal neural elements occurs ( Fig. 169.2 ).
Evaluation and Diagnosis
Referral Criteria
Primary-care physicians have recognized the need for comprehensive prospective management of achondroplastic patients for sleep, respiratory, and central nervous system disorders. , , To aid the efforts, we present our recommendations for evaluation of achondroplastic patients for cervicomedullary compression and spinal stenosis. Achondroplastic patients should be evaluated according to a standardized protocol that involves a multidisciplinary team of neurosurgeons, neurologists, pulmonary and sleep specialists, geneticists, anesthesiologists, neuroradiologists, orthopedic surgeons, and otolaryngologists. Because these patients are at risk for brainstem compression, comprehensive testing is directed toward detection of central and obstructive apnea and cervicomedullary compression, all of which contribute to the risk of sudden death.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here