It is important for the prognosis of the patient to determine and treat the patients with hydrocephaly as early as we can. However, it is sometimes very difficult to decide whether surgical treatment or follow up is needed for ventriculomegaly. Every new study will provide benefits for the treatment of this disease, which occurs at a rate of nearly 100.000 new patients every year in the world.
CCT is still the most important tool for the diagnosis of hydrocephaly. Increase in ventricule size, subependymal passage (periventricular low dansity), ballooning of the frontal horns of the lateral ventricles (mickey mouse ventricle), compression-obliteration of basal cisternae, flocculation of contours, and thining of the parenchym are the findings of imaging3. Furthermore, Evan's indexes, 3rd ventricular indexes, sella media indexes, and ventricular scores, which were defined by Mataro et al., could be measured depending on the CCT findings1. The most important treatment protocol is ventriculoperitoneal shunting. However, there may be some hesitations about the indications and the timing of shunts.
No biochemical markers for intracranial pressure have been put forth in recent years. NGF, which is a member of the neurotropin family and a molecule of polypeptide structure and described in 1951, has an important role in nerve cell development and regeneration. Its effects are produced via membrane receptors called TrkA and p75. Although several studies have shown that neurotropic factors have effects over controlling the cellular calcium hemostasis, regulating the cerebral blood flow, improving the results of cerebral ischemia, upregulating the enzymes in the antioxidation metabolism, and supression of free oxygen radicals, the mechanism in neuroprotection remains unclear. Increase in the NGF level following brain injury is the principle for neuronal healing2. NGF levels in CSF and blood have been found to be increased in cerebral pathologies like hypoxia, ischemia, injury, senile atrophy, hydrocephaly, seizures, neuro-immunological diseases and increased intracranial pressure2,4-7.
Recently, the relation between the changes in the blood and CSF NGF levels and several pathologic situations and symptoms have been investigated. However, we could not find any studies in literature on the correlation between the CCT findings and NGF levels in hydrocephaly.
When the literature was searched, it was found that NGF levels in the CSF were higher in children with hydrocephaly. Moreover, it was reported that NGF did not remain unchanged in the component of CSF, and that it played an important role in the pathogenesis of hydrocephaly5.
It has been reported that CSF NGF levels of the patients whose ventricle size and symptoms had not changed following venticuloperitoneal shunting (arrest hydrocephaly) were higher than in patients whose ventricle size and symptoms had (high pressure hydrocephaly) decreased2. Shunt application leads to an increase in NGF production in hydrocephaly patients. NGF levels in the CSF of patients who have undergone shunt application, transiently increases after 2-3 days. An increase in NGF after brain injury is crucial for neuronal healing. Despite the significant role of neurons in NGF synthesis under normal conditions, in brain injury, glial cells can produce NGF8. The increase in the postoperative CSF NGF in the first 2-3 days after the shunt application in hydrocephaly patients depends on the increased glial cells after the brain injury. Arrest hydrocephaly occurs due to the primary cortical atrophy. As many neurons in the cerebral cortex become injured and reactive astrogliosis takes place, the increase in NGF in these patients becomes more prominent and the decrease of NGF concentration occurs slowly7. The prognosis of the patients with arrest hydrocephaly after shunt operation is poor2. In our study, the mean NGF levels on the 30th postoperative day is lower by approximately 14% of the peroperative NGF levels.
In the study of Mataro et al. the effects of shunt operation on the cognitive functions in young patients with hydrocephaly were investigated. In addition, the Evan's indexes, 3. ventricle indexes, sella media indexes and ventricular indexes in the preoperative and postoperative CCT findings were measured and the correlation between them were evaluated1. It was found that ventricular sizes were decreased dramatically, and that large ventricles may be related with bad performance in verbal and visual tests. A study can be performed that would investigate the relation between the ventricular indexes and motor and cognitive functions after the shunt operation. In most of our patients, the CCT indexes decreased after the shunt operation. On the postoperative 3rd day, Evan's indexes decreased in 18 of 27 patients; the index increased in 6 of 27 patients, and in 3 patients, it remained unchanged. The third venticle index decreased, did not change, and increased in 21, 3, and 3 patients, respectively. The Sella media index decreased in 18 of 27 patients, it increased in 8 of 27 patients, and it remained unchanged in 1 patient. The ventricular score decreased in 21 patients, and increased in 6 patients. As a result, in the tomographic evaluation, a prominent decrease in the 3rd ventricular index and ventricular score can be expected. It was seen that the increase in Evan's index was parallel to the increase in ventricule score. Increased and unchanged indexes may be caused by shunt dysfunction or ventricular wall weakening due to excessive CSF or non-collapsing ventricles after the shunt operation.
Many researchers have investigated the changes in ventricular size after surgical treatment of patients with hydrocephaly. There will not be prominent changes in ventricular size in the early postoperative period in patients undergoing endoscopic third ventriculostomy, which is performed for the treatment of hydrocephaly with good results9,10. Similarly, it has been found that there will not be a correlation between the decrease of ventricular size and clinical improvements in normal pressure hydrocephaly patients who have undergone the operation in the same fashion11.
Several studies have shown that clinical symptoms are not trustworthy for predicting the intracranial pressure12,13. NGF levels were found to be increased in both blood and CSF during increased intracranial pressure. For this reason, in patients with hydrocephaly, shunt insufficiency, and craniosynostosis, tomography will not provide information about the intracranial pressure by looking at the ventricle sizes. Blood and CSF NGF levels, which can be used for the follow-up treatment of patients, can be helpful in this matter.
Infants who have had a moderate level of ventriculomegaly, will not develop hydrocephaly, because the majority stabilize spontaneously and regress. Beside these, there is a significant tendency towards cognitive and psychomotor underdevelopment, parallel to the ventricle size14,15. These children can be followed up by measurement of the NGF levels.
In our study, NGF levels and also ventricle sizes decrease in the postoperative 30th day. These parameters are meaningful in the follow up of hydrocephalus independently, because no significant correlation has been found between the CSF NGF levels and CCT indexes according to the Spearman correlation analyses. We can't say ventricule size indicates NGF level with these statistical results. As in previous studies, NGF levels on the postoperative 3rd day were significatnly higher than the levels in the preoperative period. The levels on the 30th postoperative day had not been investigated in previous studies. It was found that the decrease in NGF levels were statistically significant when compared with the level on the 3rd postoperative day, but insignificant when compared with the level in the preoperative period.
In the evaluation by tomography, it can be expected that Evan's indexes, 3rd ventricule indexes and ventricular indexes can decrease progressively. It was seen that the difference between the levels of sella media indexes on the 3rd postoperative day and that of the preoperative period were not significant, but the difference between the postoperative 3rd and 30th day was significant. Although the ventricular index was the mostly correlated index with other indexes, each of the 3rd ventricular indexes was only correlated with one index.
As a result, CCT has an important role in making a decision on the treatment and follow-up of infants with hydrocephaly. Indexes defined in tomography are also helpful. As NGF, which has important role in neuron development and regeneration, is increased in the preoperative period in patients with hydrocephaly and shows changes in the postoperative period, it can be used in neuron healing directly or used for deciding on the surgical decision, and be helpful in the follow-up. There was no significant correlation between CSF NGF levels and CCT indexes using the Spearman correlation, but it was found that each has some significant relations within each other. Measured NGF levels after shunt surgery can be helpful in the follow up of hydrocephalus. When it is not possible to decide on surgery with the CCT findings, measurement of the CSF NGF level can provide an idea. Especially if there is a risk of cognitive and psychomotor development in patients with moderate ventriculomegaly, patients can be followed up by measurement of NGF levels. Future studies on NGF, which produces effects on several systems in the organism, will be very helpful for the diagnosis and treatment of several diseases.