Chapter 184 Neurologic Problems of the Spine in Achondroplasia

Benjamin S. Carson, Mari Groves, Reza Yassari

Achondroplasia is characterized by disproportionately short stature with rhizomelic shortening of the extremities, macrocephaly, midface hypoplasia, and frontal bossing.^1,² This skeletal dysplasia results from defective formation of endochondral bone.³^–⁵ Morbidity in achondroplasia results largely from bony compression of the neuraxis⁶^–¹² and respiratory failure.^13,¹⁴ 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.¹⁵ Thoracolumbar stenosis can be accelerated in infants who develop progressive thoracolumbar kyphosis if bracing is not undertaken before vertebral wedging develops.¹⁶ Less common problems in infancy include symptomatic airway obstruction¹⁷ and severe cervicomedullary compression secondary to foramen magnum stenosis.¹⁸^–²⁰ The latter can be sometimes accompanied by swallowing difficulties and central apnea.²¹

Most individuals with achondroplasia have normal intelligence. Motor milestones are delayed,²² 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.²³ 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.¹⁴ 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.²⁴ 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,²⁵ 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.²⁶ Moreover, cardiovascular cases of death are increased in the adult group (25-54 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 ^27,²⁸; however, the true frequency may be slightly higher.²⁹ New mutations account for about 80% of children born with achondroplasia.²⁸ As in many autosomal dominant disorders, a positive correlation exists between advanced paternal age and occurrence of new mutations.³⁰ 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.³¹ 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 brain stem compression.³²

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.^33,³⁴ The protein is a tyrosine kinase receptor expressed in developing bones. The G380R mutation has been found in most patients.^35,³⁶ 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.³⁷ This impaired formation of bone from cartilage is seen in the growth of the diaphyses of long bones.³ 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.³⁸ The cranial base (chondrocranium) derives from endochondral ossification. In achondroplasia, the base is stunted, shorter, and narrower that normal.³⁹ 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 brain stem upward and the foramen magnum anteriorly, resulting in posterior tilting to the brain stem and further impingement of the neuraxis posteriorly²⁴ (Fig. 184-1).

FIGURE 184-1 Normal findings (left) compared with findings in the cervicomedullary junction in patients with achondroplasia (right). The horizontal orientation of the posterior rim of the foramen magnum in achondroplasia causes kinking of the cervicomedullary junction. The area of bone removed during the cervicomedullary decompression is depicted in green (right).

(Bagley CA, et al. Cervicomedullary decompression for foramen magnum stenosis in achondroplasia. J Neurosurg. 2006 Mar;104(3 Suppl):166-172.)

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.^40,⁴¹ 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.⁴² Abbreviated and thickened pedicles of the vertebral arches result from premature fusion of synchondroses between the laminae and the vertebral bodies³; the laminae are also thickened. Intervertebral discs tend to bulge prominently,⁴² 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,⁴³ 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.⁴⁴ Consequently, a generalized constriction of spinal neural elements occurs (Fig. 184-2).

FIGURE 184-2 Thoracolumbar spine in a pediatric patient with achondroplasia, showing the abnormal bone anatomy that leads to neural compression.

(Sciubba et al. Spinal stenosis surgery in pediatric patients with achondroplasia. J Neurosurg. 2007 May;106(5 Suppl):372-378.)

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.^14,^17,⁴⁵ To aid the efforts, we present our recommendations for evaluation of achondroplastic patients for cervicomedullary compression and spinal stenosis. Achondroplastic patients referred to our institution are usually 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 brain stem 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.

Cervicomedullary Compression

Clinical Pathology and Presentation

Cervicomedullary compression warrants early and aggressive treatment. Results of studies suggest such compression is progressive and potentially fatal because it increases the risk of sudden death by central respiratory failure.^46,⁴⁷ This condition has gained increasing attention as a cause of respiratory and neurologic impairment in children with achondroplasia.⁴⁸^–⁵⁰ In our prospective evaluation of achondroplastic infants, we found radiographic evidence of craniocervical stenosis in 58% of the studied patients, and a diagnosis of cervicomedullary compression was made in 35%.⁴⁹ These figures are for a selected population and are certainly higher that the proportion in the general population. Nonetheless, they are a strong argument for the careful evaluation and treatment of achondroplastic children. A retrospective study found excess mortality in sudden death resulting from brain stem compression, which was identified as the cause of half of the excess deaths.²⁶ The same study also found a 7.5% risk of sudden death in the first year of life.

Chronic medullary and upper cervical cord compression may exist as a neurologically asymptomatic lesion, exhibiting neither signs of root compression in the arms nor symptoms of cranial nerve impairment.⁵¹ Nonetheless, microcystic histopathologic changes, cervical syringomyelia, and necrosis and gliosis have been reported in autopsies of achondroplastic children who died unexpectedly.^19,^20,⁴⁷ Presumably, lesions of this type interrupt neural respiratory pathways from the nucleus tractus solitarius to the phrenic nerve nucleus—arresting the muscles of respiration and resulting in sudden death in some cases. We consider infants with a history of sleep apnea or other severe respiratory or neurologic abnormalities to be at increased risk for respiratory complications resulting from occult cervicomedullary compression.⁴⁹ Some authors have recommended performing sleep and imaging studies on all children with achondroplasia.⁴⁵ A composite profile of the patient with cervicomedullary compression includes upper or lower extremity paresis, apnea and cyanosis, hyperreflexia or hypertonia, and delay in motor milestones beyond achondroplastic standards. These patients can present a striking contrast to the usual floppy, hypotonic achondroplastic infants.⁵² More recently, a study indicated that although normal imaging studies may be found in achondroplastic children on magnetic resonance imaging (MRI) in a neutral neck position, flexion can lead to increased intracranial pressure (ICP) due to venous outflow obstruction and complete cerebrospinal fluid (CSF) outflow block.⁵³ The imaging findings have to be correlated with the clinical status of the patient, and the decision for treatment is ultimately guided by the patient’s neurologic status and the surgeon’s experience.

Evaluation

Once the high-risk patient with respiratory or neurologic symptoms or signs has been identified, we advise comprehensive testing. Parents should be carefully interviewed about the health and medical history of the child, with emphasis on respiratory symptoms, and a general physical examination, including chest measurements, should be performed. Respiratory evaluation should include the evaluation of blood pH, a chest radiograph, and overnight polysomnography. Electrocardiograms and echocardiograms should be performed to see whether there is cardiac evidence of chronic oxygen deprivation during sleep. A neurologic examination for signs of brain stem compression, such as hyperreflexia, hypertonia, paresis, asymmetry of movement or strength, or abnormal plantar response, is essential. Brain stem auditory evoked potential and upper extremity somatosensory evoked potential evaluation should be considered as an adjunct, especially in patients with normal results on neurologic examination.⁵⁴ Imaging studies of the craniocervical junction are necessary, particularly MRI in the sagittal plane. We also strongly recommend MRI flow studies of the CSF at the foramen magnum, using the technique of synchronizing the succession of images with the heartbeat. Some of these procedures have been described elsewhere.⁴⁹

Indication for Surgery

The underlying principle for surgery must be to identify patients who are at risk for neurologic damage or sudden death. We recommend that patients with cervicomedullary compression be identified and treated prophylactically, before abrupt and irreversible changes occur. For the purpose of diagnosis, we define clinically significant cervicomedullary compression to be (1) neurologic evidence of upper cervical myelopathy; (2) evidence of stenosis on imaging studies, including the absence of flow above and below the foramen magnum; and (3) an otherwise unexplained respiratory or developmental abnormality. It is possible to see a patient with brain stem compression and obstructive apnea who nonetheless meets these criteria. Having discovered these indications, the treatment team should also ask whether the patient’s status is stable or deteriorating before undertaking operative decompression and should evaluate the probability for catastrophic deterioration if decompression is not performed (Fig. 184-3).

FIGURE 184-3 Preoperative T1-weighted (left) and T2-weighted (right) MRI demonstrating the typical findings in the craniocervical junction in patients with achondroplasia. The horizontal orientation of the posterior rim of the foramen magnum causes kinking of the cervicomedullary junction. Note the lack of CSF space at the level of the foramen magnum caused by the bone compression.

(Bagley CA, et al. Cervicomedullary decompression for foramen magnum stenosis in achondroplasia. J Neurosurg. 2006 Mar;104(3 Suppl):166-172.)

Operative Management

Craniocervical surgical decompression for cervicomedullary compression in children with achondroplasia ⁵⁵ has been used at several centers with generally good results.^12,^21,⁵⁶ Decompression of the cervicomedullary junction has shown to bring about dramatic, sustained improvement in neurologic and respiratory compromise.^49,⁵² The procedure has not received as wide acceptance as it might, however, because its successful performance relies on careful management of the anatomic difficulties presented by achondroplastic patients. Clinical evaluation is frequently difficult for many reasons, some of which are unrelated to neurologic compromise. Long-term follow-up data that would allow a definitive assessment of craniocervical decompression have also been lacking. As with any surgical procedure, detailed prior consultation must be conducted with the parents to inform them of the potential risks and expected benefits for their achondroplastic child.

A large operating room is used to accommodate all the equipment and personnel necessary for decompression of the craniocervical junction. Before coming to the operating room, patients are sedated and antibiotics are administered. Patients also receive steroids preoperatively to protect the spinal cord and brain stem from local trauma. Patients are positioned prone on the operating table with the head and neck carefully supported in slight flexion by use of a padded pediatric horseshoe headrest. Upper extremities somatosensory evoked potential responses are assessed routinely during positioning, as well as during the decompression procedure.

For decompression, a midline suboccipital incision is made, and the ligaments and musculature are dissected subperiosteally to expose the occiput and the spinous process and laminae of C1 and C2. The arch of C1 is then removed with a high-speed drill and small curettes. The surgeon frequently sees a thick, fibrous band or pannus about the level of C1 that should be left in place during the initial bone drilling to create a protective layer for the underlying dura and spinal cord. Removal of the arch of C2 is sometimes necessary; more caudal areas of compression necessitate even further caudad decompression. The posterior rim of the foramen magnum is thinned gradually with a high-speed drill and removed with small, straight, and angled curettes. Invariably, the bone of the foramen magnum is thickened and oriented more horizontally than usual, severely indenting the underlying dura. The most delicate part of the dissection occurs as the drill approaches the posterior rim of the foramen magnum. Once bone decompression is complete, the fibrous pannus or band is removed as well, often revealing the transverse dural channel that offers dramatic evidence of the extent of the dural restriction; consequently, adequate attention must be paid to the soft tissue aspects of the decompression. We used to perform duraplasty routinely with the placement of a dural patch. However, more recently, this step of the procedure has been only required if there is any persistent dural constriction after the fibrous band has been removed. After a duraplasty is performed, adequate cord pulsation and CSF flow are confirmed. A dural patch can be performed using pericranium, paraspinal fascia, or cadaveric dura. A watertight seal is essential. We do not recommend the placement of a wound drain so as not to potentiate the development of a CSF fistula; however, if the dura is opened, it is wise to place a ventriculostomy, because many patients with achondroplasia have increased ICP and will experience CSF leak and possible pseudomeningocele if the duraplasty is challenged early.

Somatosensory evoked potentials are evaluated throughout the procedure and before the patient is undraped, in case a decision is made to reexplore the wound. Once movement is confirmed in all four extremities, the patient is sent to the pediatric intensive care unit. Extubation is often performed immediately postoperatively; however, in some cases, facial and laryngeal edema make this procedure inadvisable for 12 to 24 hours. After surgery, primary attention is directed toward monitoring ICP as a part of postoperative nursing care if a ventriculostomy was placed.

The surgeon should bear in mind several important pitfalls when undertaking cervicomedullary decompression in achondroplastic patients. First, the patient’s head must not be overflexed during positioning, because such a position often reduces the subarachnoid space at the cervicomedullary junction. Second, the surgeon should avoid placing any instruments beneath the posterior arch of C1 or beneath the rim of the foramen magnum (such a Kerrison rongeur), even if the patient is pretreated with steroids. There is already a tremendous amount of constriction and pressure over the cervicomedullary junction, and even the brief introduction of an instrument in that area can be disastrous. The spinal cord and brain stem of these patients are small; hence, the decompression should be correspondingly small. The surgeon must have in mind an accurate conception of the size of the underlying neural elements to perform an appropriate decompression. A careful preoperative examination and study of the MRI are essential. The decompression must be extended not only along the dorsal surface of the cervicomedullary junction but also sufficiently along the lateral dimensions of the medulla to decompress the stenosis adequately at the level of the foramen magnum.

Frequently, engorged veins exist beneath the ligamentum flavum, located dorsally and laterally, and sometimes insinuate through the ligamentum flavum. These veins can create enormous bleeding and must be controlled rapidly if they are compromised. The possibility of an air embolism exists, and the surgeon should ensure that the patient is not in any degree of reverse Trendelenburg position. Finally, once the bone decompression is complete, the underlying dura, which in many cases is severely constricted, must be carefully checked. The dura is often fused with the ligamentum, and this soft tissue band constricts the underlying neural tissue, even without the presence of the overlying bone. In this case, the band needs to be divided (and a duraplasty should be performed), and then a patch is placed. Attention should be paid during duraplasty to a significantly engorged annular sinus commonly present beneath the foramen magnum. In the case of bleeding from the sinus, appropriate measures are necessary for meticulous hemostasis.

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