Rethinking the role of endoscopic third ventriculostomy in the treatment of hydrocephalus in achondroplasia

INTRODUCTION

Ventriculoperitoneal (VP) shunting has historically been used to treat hydrocephalus in achondroplasia since it was believed to be of the communicating type. Studies have revealed that the anatomical configuration is that of the “triventricular” variety, nevertheless. Endoscopic third ventriculostomy (ETV), albeit being controversial, is used as a mode of cerebrospinal fluid (CSF) diversion in children with achondroplasia and has proven to be successful.^[1,2]

In the current study, we present the outcome of one such child who had achondroplasia with hydrocephalus. The child was successfully treated by ETV. We also review the relevant literature supporting this opinion.

ILLUSTRATIVE CASE

An 8-month-old child was referred by a pediatrician with complaints of progressive increase in head size noted to be significant over the past 4-month duration. The child had short, stout extremities, macrocephaly. Parents complained of irritability and episodes of vomiting and had recently developed obstructive sleep apnea. He did not have the anterior fontanelle that was full but not tense. The head circumference had changed trend from the time of birth (tracing done both on regular and achondroplasia head circumference growth charts) and was greater than 2 standard deviations of the normal trend. The fundus examination revealed early papilledema. The child had achieved all normal developmental milestones.

Imaging revealed dilated lateral and third ventricles with a normal fourth ventricle. He had stenosis of the foramen magnum associated with the hydrocephalus. He underwent ETV at 8 months of age, following which he had significant clinical improvement. He became active, and his sleep apnea was cured. He was followed up at 2 years of age when the trend of growth of his head circumference had plateaued. He had achieved all the age-appropriate milestones. His follow-up imaging showed reduced size of the ventricles and patent third ventriculostomy [Figure 1].

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Figure 1:

(a) Preoperative imaging showing dilated ventricles with stenosis at the foramen magnum and dilated cerebrospinal fluid spaces. (b-e) Intraoperative images showing the floor of third ventricle with ventriculostomy opening. (f) Postoperative imaging at 2 year of age showing patent ventriculostomy (arrow showing flow void) and decompressed ventricles.

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DISCUSSION

Achondroplasia is the most prevalent skeletal dysplasia, occurring in approximately 1 in 25,000–30,000 live births. Although it is an autosomal dominant disorder, about 80% of cases are sporadic. It is an abnormality of chondrocyte formation that is caused by gain-of-function mutations in fibroblast growth factor receptor 3, resulting in a decreased rate of endochondral ossification and unimpeded periosteal bone formation, leading to the characteristic conspicuous abnormalities of the axial skeleton.^[2-5]

The skull base is relatively small, with a narrowed foramen magnum and shortened clivus and skull base foramina. Numerous spinal defects, such as small and narrow vertebral bodies with shortened pedicles, ligamentous hypertrophy, thoracolumbar kyphosis, and lumbar hyperlordosis, are commonly seen.^[3,5-7] The resulting compressive forces, bony abnormalities, and defective enchondral ossification along the neuraxis can result in conditions such as hydrocephalus, cervicomedullary compression, syringomyelia, spinal canal stenosis, instability, and entrapment neuropathies.^[4,6,8]

Hydrocephalus is noted in about 15–50% of cases.^[1,3,7,9] The reason is due to a combination of a narrow skull base, which leads to compression of the basal cisterns and pressure gradients across the jugular foramen and dural venous sinus. The other contributing factors are foramen magnum stenosis with fourth ventricle outflow obstruction, posterior indentation of the cord at the level of the foramen magnum, and jugular vein at the thoracic inlet. The cumulative effects of all these factors eventually result in dural venous sinus hypertension, leading to decreased CSF absorption, ventriculomegaly, and ultimately resulting in hydrocephalus.^{[2-4,7,10,11]} Some instances include noncommunicating hydrocephalus brought on by stenosis of the sylvian aqueduct or restriction of the fourth ventricle’s CSF outflow.^[2,12]

This chronic raised intracranial pressure (ICP) in due course leads to the development of venous collaterals as well as venous circulation through the emissary veins that eventually stabilizes CSF buildup. This eliminates the need for intervention in most cases.^[1-3]

Hence, it is crucial to distinguish between clinically significant hydrocephalus from compensated hydrocephalus. All achondroplastic children should have their head growth monitored using serial head circumference measurements plotted on achondroplasia-specific head circumference charts. Since sutural development is delayed in achondroplasia, measurements of the head circumference and fontanelle should be taken until the child is at least 5–6 years old.^[5,13]

Hydrocephalus in such children presents insidiously. Hence, all patients with enlarging head circumference and signs or symptoms of elevated intracranial pressure should be evaluated using magnetic resonance imaging (MRI) with CSF flow studies. Various parameters, such as ventricular size, aqueductal stenosis, CSF outflow obstruction, foramen magnum stenosis, and transependymal CSF flow, should be specifically looked for. Cranial ultrasonography is considered to be an adequate screening test in a child with an open fontanelle, where MRI is not feasible or available.^[3,14]

Achondroplastic patients generally have an enlarged head as well as ventriculomegaly, which later has a spontaneous arrest. Intervention is thus considered only in symptomatic patients.^[2,3] Generally, an Evans ratio of at least 0.30 has been used to diagnose hydrocephalus in individuals of average stature. However, Kashanian et al. and Reina et al. in their respective studies have opined that a ratio of at least 0.50 may have a higher likelihood of being indicative of progressive, symptomatic hydrocephalus requiring surgical intervention.^[14,15] A judicial and detailed selection process should thus be used to determine which patient requires intervention, especially considering the high rate of complications and revision procedures in this patient population.

Conventionally, ventriculo-peritoneal shunting has been the treatment of choice in these patients. Nonetheless, shunts are associated with a high rate of shunt malfunction and require multiple revisions in this patient population.^[2,3,6,9] King et al. reported that 4.3% of children with achondroplasia under their care required shunting. They have reportedly performed 40 shunt revisions in 11 patients with achondroplasia.^[6] Kim et al.^[1] reported 7 out of 9 patients with VP Shunts undergoing a total of 47 revisions. The probable cause of this repetitive shunt failure is proximal malfunction. The reduction in ventricular size and collapse brought on by the enlarged brain are caused by the relative cerebral venous engorgement that develops as a result of the dural venous sinus hypertension. This compromises the patency of the ventricular catheter, resulting in shunt malfunction.^[6,9]

Etus et al. had initially suggested the possibility of ETV as a feasible modality in 2 patients with achondroplasia. Swift et al. in their initial article reported three cases of hydrocephalus with raised ICP features in children with achondroplasia treated with Foramen magnum decompression. He reported improved symptoms and decreased ventricular size following ETV in all three patients.^[7] In his recent article, Kim and colleagues reported long-term results of 12 patients with achondroplasia (of which 3 were the ones reported in the first series) who underwent ETV. All 12 patients demonstrated good clinical outcomes with objective reduction of ventricular size.^[1] King et al. in 1 patient with chondroplasia who presented with intractable headache due to hydrocephalus; the headache subsided following surgery.^[6] Shoda et al. reported a case of an 18-month-old boy with Achondroplasia and developmental delay.^[2] Post ETV, on 10 months follow-up, the patient’s developmental quotient score improved to 100.^[2]

Further analysis makes it evident that achondroplasia has a dual component of both communicative and obstructive hydrocephalus. The presence of a preexisting dilated aqueduct (communicating component) along with a relatively smaller skull base (due to the aberrant enchondral ossification) brings upon this dual pathology. The venous congestion brought on by dural venous sinus hypertension causes cerebellar engorgement. This imbalance between the vault and parenchyma causes compression of the cisterna magna and tonsillar herniation, which prevents CSF outflow from the fourth ventricle, contributing to the obstructive component of this dual pathology of hydrocephalus.^[9,16]

The minimum age during surgery in all prior papers was 11 months.^[17] In addition, the success rates of ETV in treating aqueduct stenosis in children older than 6 months are comparable to those of VP shunting, providing the advantage of avoiding shunt-related complications. Morphology of the third ventricle is another important aspect that predicts the outcome of this procedure. The MRI findings that can predict ETV success in the general population are progressive ventricular enlargement, bowing of the floor of the third ventricle inferiorly into the interpeduncular cistern, displacement of the lamina terminalis anteriorly into the lamina terminalis cistern, and distention of the proximal sylvian aqueduct.^[1,16] These findings, when found in achondroplastic individuals, add merit to the decision of ETV. Thus, making ETV a safer management strategy in children with Achondroplasia.

Etus et al.^[17] and Kim et al.^[1] in their studies have reported having difficulties while performing an ETV due to anatomical variations of the third ventricle. The third ventricle’s floor can be vertical, which makes perforation extremely challenging and risky since it increases the possibility of inadvertent damage to the surrounding neurovascular structures, such as the pituitary or the Hypothalamus. Hence, meticulous preoperative planning is warranted.^[1]

CONCLUSION

The timing of surgical intervention in achondroplasia patients with hydrocephalus is uncertain. Current recommendations advise surgery for symptomatic or progressive cases, but determining symptoms in young children is difficult, and the age at which the initial neuroimaging study is acquired determines the progression. As there is an element of uncertainty whether the hydrocephalus is due to obstructive or communicating or dual ETV is suggested as a first modality. This also gives an opportunity to avoid complications and poor outcomes of VP shunts. However, more research is needed to confirm this through clinical trials.