It has been proposed that the presence of hydrocephalus in children with myelomeningocele (MMC) can be an indication of a decreased intelligence quotient (IQ). Others have argued that it is not the mere presence of hydrocephalus but the superimposition of CSF infections, multiple shunt procedures, and other CNS complications that lead to the decreased IQ observed in these patients. In this paper, we review different studies to better discern the IQ in patients with MMC and if it changes after infections and shunt procedures. We also have a glance at other factors that might play a role in IQ development in these patients and the differences observed in brain imaging of individuals with MMC.
Keywords; Myelomeningocele, spina bifida, hydrocephalus, intelligence quotient, venticuloperitoneal shunt
Myelomeningocele (MMC) is the most serious form of spina bifida with a prevalence of about 1 per 1,000 births globally [6, 23]. The pathogenesis of MMC has been proposed to be multi-factorial, although its association with maternal folate deficiency is well known [6, 24, 33]. While compatible with life, children with MMC tend to have a lower quality of life compared to normal individuals mostly due to the central nervous system impairment associated with this disorder. Spinal cord defect in children born with MMC can present as either sensory or motor deficits with extreme cases causing an impairment of mobility .
Cranial abnormalities can also present in individuals with MMC. This might be attributed to the similar embryological structure, the neural tube, from which both the brain and the spinal cord develop during embryogenesis. Some well-known abnormalities associated with the brain in individuals with MMC include hydrocephalus, corpus callosum dysgenesis and Chiari II malformation, which itself is a cause of hydrocephalus [6, 18, 19, 24, 28, 37]. These abnormalities have been linked to a variety of learning disabilities as well as decreased executive functioning in these individuals [18, 21, 24]. The presence of hydrocephalus has been proposed to be a significant predictor of intellectual capacity in MMC patients and most studies on IQ and executive functioning in these individuals have been focused on hydrocephalus with or without ventricular shunting [3, 9, 17, 26, 30]. Complications secondary to ventricular shunting have also been postulated to worsen intellectual function .
Intelligence Quotient and Myelomeningocele
Intellectual capacity is an important factor by which an individual’s survival quality may be evaluated. Therefore, it is of great importance we know how the intelligence quotient (IQ) of children with MMC is being affected by the subsequent death of neuron in-utero [19, 30]. Several studies have been performed to see how IQ is affected in children with MMC [3, 9, 10, 11, 17, 19, 21, 24, 27]. Many of these studies demonstrate how hydrocephalus in children with MMC can be a negative predictor of intellectual capacity, which in tandem, is detrimental to the quality of life in these patients . In one of the earlier studies performed by Mapstone et al., a significant difference in intellectual function was observed when comparing the IQ of MMC children with and without hydrocephalus . Children with hydrocephalus were noted to have a low-normal IQ whereas those without were in the normal range. Similar conclusions were drawn from an identical study performed by Soare and Raimondi, where they observed 173 children with 133 having developed hydrocephalus and the remaining 40 presented swelling-free . Their results showed about 63% of children with hydrocephalus had an IQ greater than 80, which in this study was considered normal. However, 87% of children without hydrocephalus had similar results albeit with a smaller sample size. When compared with their siblings, children with hydrocephalus scored notably lower on a test for accessing perceptual-motor function.
Soare and Raimondi also observed that individuals with a higher level of spinal cord lesion tended to have a lower IQ when compared to their counterparts with a lower level lesion . This was again almost identical to that observed by Mapstone et al. in that they did see an inverse relationship between IQ and lesion levels, but deemed the results statistically insignificant . However, results from Nejat et al., contradicted the above findings with their study showing no significant correlation between the level of the lesion and IQ . Could this be attributed to a much smaller sample size of 50 children in this study compared to the former with 173 or were Mapstone et al. right when they considered the relationship to be insignificant? More studies would be needed to provide a definite answer to this hypothesis.
Several other studies have demonstrated the relationship between decreased cognitive function and hydrocephalus in individuals with MMC [9, 10, 17, 30]. One major inclusion from the study by Hampton et al was that although children with spina bifida do perform poorer in tasks involving spatial and executive function, their performance in vocabulary related task was relatively higher . This might not mean much as children without MMC used as control also performed much better in verbal related tasks compared to spatial tasks and might just suggest a general trend.
It is worthy of note that although executive functioning, learning and memory-related tasks might be impaired in patients with MMC, emotion recognition is also deemed to be negatively affected and some studies have argued that performance in visual tasks involving object based visual processing might be intact in these patients [31, 34]. Arnold Chiari-II malformation, which is mostly present in children with spina bifida, has been proposed to negatively affect both performance IQ, verbal IQ and visual related tasks in patients with MMC .
Is hydrocephalus alone, when present in individuals with MMC, the sole predictor of IQ? Probably not. A study by McLone showed that children with complicated hydrocephalus (i.e., hydrocephalus along with other CNS insults such as ventriculitis, meningitis, and an increase in revision of shunts) tended to have significantly lower IQ when compared to previously recorded intellectual functioning scores . However, children with hydrocephalus (+/- shunt) but without complications had scores similar to their previous record. Other studies have had similar results associating more frequent shunt revisions and complications with poorer functional outcomes [13, 20]. McLone also observed a slight correlation between lesion location and infection rate such that children with a higher lesion had a higher incidence of infection and therefore a lower IQ .
A lower socioeconomic status (SES) has been generally assumed to occur simultaneously with a lower IQ [11, 32]. It is therefore of no surprise to inquire about the IQ of children with MMC born into a low SES family. A study was performed by Swartwout et al. to discern the relationship between MMC children, IQ, and SES . Although this article does not compare the IQ difference between children with and without MMC with lower SES as the common variable, the results of their study demonstrated that a lower socioeconomic status in children with MMC is associated with a lower “verbal” IQ, which in turn tends to lead to a lower IQ. .
Cortical organization and imaging of the brain in MMC
IQ is a measure of cortical function and visualizing the differences in cortical organization and overall brain topography in patients with MMC can assist in further understanding this disorder. It has been postulated that the cerebral cortex in individuals with MMC has an atypical organization leading to a derangement in motor and cognitive function . Although heritability does play a prominent role in IQ development, research have shown that people with higher IQ tend to have a prolonged period of cortical thickening during childhood . But how does an atypical arrangement of the cerebral cortex lead to a perturbed cognitive function and what physical characteristics are seen in the cerebral cortex of these individuals and how do these relate to IQ? To investigate this conundrum, Treble et al. performed a study to show how cortical thickness relates to IQ and fine motor function in MMC . Their perspective was that since a significant amount of neuro-cognitive disorders have an association with atypical brain volume, how does the unusual organization of the cortex in individuals with MMC relate with the thickness of the cortex? The relationship between the thickness of the cerebral cortex and IQ in individuals with MMC was studied as well as whether an upper or lower limit to cortical thickness and gyrification exists for ideal motor and cognitive function in these individuals . High resolution magnetic resonance images (MRI) of the brain were taken 64 patients with MMC and compared with 24 normally developing controls with each individual undergoing IQ and fine motor dexterity tests and results match for their respective age groups. Temple et al. observed that there was a negative correlation between IQ and increased cerebral thickness in individuals with MMC, and stipulated that the more the increase in cerebral thickness, the lower the IQ observed, resulting in poorer fine motor and cognitive function. On the other end of the spectrum, there was a positive correlation between a reduced thickness of the cerebral cortex and IQ. They concluded that the more the deviation of the cortical thickness from the norm, the lower the IQ .
Another imaging study showed a remarkable decrease in white matter and a corresponding increase in cerebrospinal fluid (CSF) of the brain in children with MMC . Their result suggested a decreased myelination and disruption of white matter pathways secondary to hydrocephalus. This supports the consensus that hydrocephalus is associated with an increase in IQ deficit observed in patients with MMC plus hydrocephalus when compared to individuals with MMC but without hydrocephalus. The negative effect of hydrocephalus on development of the brain in both humans and animals, with impact such as neuronal disruption and cellular death, is well documented, hence it is of no surprise that IQ deficits are more pronounced in individuals with MMC + hydrocephalus . Another supporting evidence of the detrimental effect of hydrocephalus on learning and executive functioning was a study by Lindquist et al which showed that there was no significant different in these cortical processes when comparing children with MMC plus hydrocephalus and children with hydrocephalus secondary to other causes with both having similarly low scores on tests for executive function compared to normal children .
Treatment of Hydrocephalus in MMC and how it affects IQ
Since the consensus appears to be that children with MMC tend to have a sub-average IQ, and the presence of hydrocephalus in patients with MMC carries a negative IQ prognosis, it is important for us to know how or if these children improve after treatment. The MMC lesion can be repaired via a variety of surgical techniques . Surgical treatment for MMC has been on the decline in the past two decades due to public awareness about folate supplementation before and during pregnancy . The argument about prenatal versus postnatal repair of the lesion is an ongoing debate in the literature, and most clinicians favor the former since it reduces the need for VP shunt placement [1, 7, 29]. Hydrocephalus tends to be one of the ever-present complications of MMC and although fetal surgical repair of the MMC lesion is a mainstay of treatment, the presence of hydrocephalus might require the placement of a ventriculoperitoneal (VP) shunt. Hammock et al. were one of the first to conduct studies on what course the intellectual performance and IQ take after surgery . All their patients, eight of them ranging from 30 months to 13 years and 5 months of age, had ventriculomegaly along with the MMC lesion but no apparent symptoms or signs of an increased intracranial pressure. The patients underwent psychological testing along with cranial CT preoperatively as well as continuous monitoring of their intraventricular pressure. Each of the patients underwent ventricular shunting and then underwent psychological testing postoperatively. Hammock et al. observed that over a period of 1 to 3 months, there was a reversal and stabilization in the downward trend on intellectual performance in these children with a noticeable improvement in performance IQ in 1 of the patients within 6 months. In a 9-month period, all the children but one had a significant improvement in their IQ scores . A much more standardized test was performed by Mapstone et al. where the patients were divided into three groups . Group I included children that never required shunting, group II were children with shunting but without any CNS complications (such as ventriculitis and anoxia) and group III were children requiring shunting but with CNS complications. Mapstone et al. observed that there after CSF shunting, the average IQ for children who never required shunting (Group 1) was much higher compared to the other two groups. Children in group II also had a higher IQ average compared to those in group III, but the difference was much larger compared to group I vs group II . They concluded that the downward trend in IQ seen in patients in group III can be attributed to the shunting complications or infections. Does this mean that if shunting complication or infections are minimized, these children will have a similar IQ to their counterparts in group II? This was exactly what was observed in another study by Arrington et al., who showed that repeat in shunt revisions can be associated with reduced cognition .
The result from most studies has shown that the IQ loss in children with MMC is an inborn error that occurs early during embryogenesis, thereby no amount of treatment or correction performed can correct the IQ deficit to normal [4, 20]. However, hydrocephalus if corrected early on, can prevent further worsening of the patients IQ functioning and return IQ to baseline for MMC patients .
The debate remains about the causes of the low IQ observed in many patients with MMC. Some have proposed that prenatal repair of the MMC lesion reduces the need for ventricular shunting after birth, and thereby decreases the risk of shunt complication and CNS infection, which normally have a negative prognosis on IQ if present. The general idea remains that patients with MMC, with or without complications, tend to have a lower IQ when compared to those without the lesion. Hydrocephalus appears to further increase the IQ deficit in patient with MMC and some studies have shown that if quickly corrected, IQ can return to baseline but not normal levels. More studies are needed to evaluate what other risk factors, apart from folate deficiency, and genetic factors might play a role in the development of MMC and how these factors might impact on the patients IQ. This is necessary to be able to fully understand, prevent and better care for children born with this disorder.
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Functional outcome in young adults with spina bifida and hydrocephalus.
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[Article in Portuguese]
Fobe JL1, Rizzo AM, Silva IM, Da Silva SP, Teixeira CE, De Souza AM, Fernandes A.
Myelomeningocele occurs in 0.4 for 1000 neonates and is associated with hydrocephalus in 85-90%, and reports on cognition are sparsely found in literature. Forty five children with treated hydrocephalus and myelomeningocele were studied in regard of IQ, and statistically correlated to functional motor level, age of the first shunt, number of revisions of shunt, infection of the shunt and circumference of the head. The medium age was of 7.5 years (3-15 years), 16 males and 29 females. Three (6.6%) had a IQ score > 110, 11 (24.4%) had a score between 100-110, 8 between 85-100 (17.7%), 16 (35.5%) between 85-100 (17.7%) and 7 (15.5%) between 50-70. IQ directly correlated with motor level, having better cognitive results the children with minor functional motor disabilities. Cognition was best in children operated until the seven day of life (t 0.0099), with progressive worse results in children operated after the first month of life, no significance was observed in children operated in the period 7 to 31 days (t 0.1013). Worse results were observed in the group of patients with infection of shunts (t 0.0146). Results were progressively worse with reoperations. The best results in relation of the circumference of the head were seen with children in the medium range (t 0.0115); intermediate results were seen in patients between the medium range and-1SD (t 0.00130) and medium range and +1SD. The worse results were seen in patients at the extremes of > 1SD (t 0.0269) and < ISD (t 0.0042). According to cognitive results the surgical treatment of hydrocephalus have to be done until the first month of life, avoiding reoperations and infections that have unfavorable impact in IQ.
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