IIH is a serious disorder with significant implications that may eventually cause permanent visual impairment along with additional characteristic clinical sequela as ultimately described above. The natural history and clinical course of pediatric IIH are not well established, and different predicting factors for the clinical course and prognosis have been investigated. Though the condition has been known for over 80 years, data regarding the quality of the management of pediatric IIH is missing, and there is no standardization of follow-up and treatment protocols30,31,32.
This multicenter study describes the clinical presentation, disease course, and prognosis of children diagnosed with IIH and investigates the correlation between the type of follow-up and the long-term disease course and outcome, manifested as unscheduled IIH-related hospital returns (ER visits and re-hospitalizations).
Our cohort is comparable to other cohorts of pediatric IIH patients regarding age, gender distribution, demographic features, clinical presentation, and disease course21,33. Similar to other studies, we noted a higher prevalence of boys and a lower rate of obesity in the prepubertal group, along with female and obesity predominance in the pubertal group6,11,15,19,34,35. Follow-up group A consisted of a higher rate of boys, possibly explained by the younger age of male patients in the cohort. Clinical features, including LP opening pressure, were similar among the gender groups. Accordingly, boys in our cohort seem to have a favorable outcome, though the difference is not significant. Nonetheless, this variance may result from the relatively small group size. However, in our study, age, gender, ethnic origin, puberty state, obesity, and CSF opening pressure at diagnosis did not influence the prognosis.
We did not find a correlation between pubertal state (as well as older age) and worse prognosis, as reported by Stiebel-Kalish et al.36. Different outcome measures may explain this difference. We used unscheduled admission as a marker of uncontrolled IIH, and in Stiebel-Kalish’s study, by the visual outcome. Similar to Sheldon et al. et al. findings, obesity was more prevalent in pubertal patients in our study33. However, neither age nor obesity were associated with poor prognosis in our study. It is possible that our groups were too small, and the type of follow-up was significantly more in determining the outcome than any other factor.
It is important to note that the clinical definition of “poor outcome” may not align with patient experience. A future study that incorporates a measure of patient-reported disability (analogous to PedMIDAS score in migraine populations) should be carried out.
Time to clinical resolution (i.e., resolution of headache and visual complaints) in our study was, on average, 2.22 ± 2.84 months. This is similar to the reported time to resolution by others.6,21,23 Papilledema resolution was documented after the mean of 7.8 ± 8.9 months in the multidisciplinary tertiary center follow-up group. This data was not available for most of the group B patients. Time to papilledema resolution in other studies varied between 4.2 and 5 months21. This difference may be explained by more frequent visits, treatment protocols, or different definitions of papilledema resolution.
Factors affecting CSF opening pressure in children have been investigated, with inconsistent findings through different studies. Higher CSF opening pressure was found in correlation with older age and obesity36,37,38,39,40. This study found that a higher weight percentile was weakly correlated with higher CSF opening pressure. However, consistent with other reports, no correlation was found between gender or age and CSF opening pressure10,19,21,37,39.
In agreement with our initial hypothesis, we found that children who were under the care of a multidisciplinary team in a tertiary center had significantly lower odds of returning to the hospital, a lower rate of resulting inpatient days, as well as longer time intervals between hospital returns, compared to children followed by individual specialists elsewhere. Furthermore, though not statistically significant, the rate of repeat LPs was lower in the group with multidisciplinary follow-up.
Although not specifically evident from the data collected within the frame of this work, it is most probable that non-concordance with follow-up (i.e. group B) reflects as well a general non-concordance manner, including adherence to medication plans. This in itself may carry with it adverse effect outcomes and eventually lead to “poor outcome “, which was associated in this work mainly with the lowest quality of follow-up.
Indeed, several publications have suggested that before, but to the best of our knowledge, this is the first study that confirms that assumption21,41,42. This finding is likely related to several advantages of tertiary center clinics, where pediatricians, neurologists, ophthalmologists, and other IIH-related specialists work in concert. This multidisciplinary approach improves the outcome of children with IIH compared to follow-ups by specialists in other settings. Moreover, greater availability of diagnostic tools, better collaboration between the different specialists taking care of the patient, no need for making separate appointments with different doctors, and immediate access to laboratory and imaging studies lead to faster management adjustments if needed.
Several other explanations for this identified difference between follow-up groups might be that group B contained more private practice providers who recommended ER visits because they were unable to accommodate them in the clinic. Alternatively, private practice providers may teach patients to go first to ER for issues. Unfortunately, we do not have data on unplanned clinic visits that may have been an alternative to a visit in the ED. There is a place for additional, comprehensive prospective future study.
IIH-related hospital returns in our study were usually derived from continuation or relapse of IIH symptoms as well as treatment-related adverse events. We assume that treatment failure is associated with poor outcomes and will likely lead to ER visits and hospitalizations due to the continuation or recurrence of symptoms. In addition to improved prognosis, appropriate care prevents other aspects of ER visits and hospitalization. They are associated with significant impairment of quality of life for the child and his family, risk of infection, and financial expenses to the health system43,44. Thus, minimizing these events is crucial and may be achieved using appropriate long-term management.
A recent study estimated the financial burden of pediatric hospitalization as 2,192 USD (mean individual medical cost) for the entire hospitalization period45. In Israel, the direct cost of a pediatric ER visit and inpatient hospitalization day are 280 and 1000 USD, respectively (charges defined by the Israeli national health system (NHS))46. Additional effects include loss of income and non-medical expenses, estimated at a median of 51 USD per day. The economic impact is more significant in lower socioeconomic populations than in others47. Based on this data, the multidisciplinary tertiary center follow-up in our study (follow-up group A) saved the NHS about 58440 USD (23 ER visits and 52 inpatient days), as well as considerable non-medical expenses, significantly among families in the low socioeconomic status. In follow-up groups A and B, the direct medical expenses due to ER visits and re-hospitalizations were 1000 and 1900 USD per inpatient day, respectively. Of note, this difference is likely to be even more significant since most hospitalization days in group A were due to a single patient.
IIH-related hospital returns in our study mainly occurred during the first year after diagnosis. Hence, follow-up evaluations should be more frequent during the first year of the disease course to prevent recurrent hospital returns, with longer intervals in the following years. However, some occurred several years later (up to 5.4 years after the diagnosis), emphasizing the importance of long-term follow-up.
The main strength of this study is its multi-center scope, detecting pediatric IIH cases from all three medical centers in Jerusalem and the surrounding area, and providing medical care for more than 400,000 children. As mentioned earlier, selection bias was minimized by covering all hospitalizations in the Jerusalem area.
One of the study’s significant limitations is its retrospective nature and the dependence of data collection on the quality of computerized documentation. Thus, we reluctantly used weight percentiles to define obesity rather than BMI because height is not routinely recorded in the pediatric emergency department. Age was used to determine puberty since the Tanner stage is not routinely documented. Furthermore, data on pediatric patients who did not have a follow-up in tertiary centers (follow-up group B) was limited. It was not possible to fully characterize their management and the course of their disease.
A gender imbalance characterizes our two compared research groups as described above. This may serve as s a potential confounder. A future large-scale study may eliminate this bias and shed light on the contribution of gender to follow-up adherence and treatment compliance.
Finally, we had only partial information about ophthalmological assessment, such as the visual field and optic nerve function. Hence, further prospective studies are desired and may add information on the ophthalmological natural course and management-related outcomes.
Based on the results of this work, we assigned a designated clinic coordinator, who is in charge of scheduling appointments for newly diagnosed patients with IIH prior to their hospital discharge and helping with any future challenges in attending clinic appointments. Moreover, the same pediatric neurologist and pediatric ophthalmologist follow the patients long-term, and the clinic visit is now executed jointly in the same room. A future study to assess the outcomes after the implantation of the described improvements is warranted.
In conclusion, this study provides new insight into the clinical course and management of pediatric IIH patients. Poor disease control may lead to unscheduled IIH-related hospital visits that may occur shortly after the initial diagnosis or even years later. Decreased rates of recurrent IIH-related hospital returns and hospitalization days and longer time to hospital returns were related to multidisciplinary follow-up in tertiary center clinics compared to follow-up in community clinics.
This retrospective study has generalizability (external validity) quality since it surveyed various parameters of a diverse, heterogeneous population of subjects (age, gender, ethnicity, etc.) comparably in both study groups. Based on these findings, this study provides insight into how hospital/medical systems can design care models to serve patients and avoid high healthcare costs associated with emergency room/inpatient visits. Long-term, coordinated follow-up by a multidisciplinary team in a tertiary center probably improves pediatric IIH patients’ life quality, decreases hospital-acquired infections, saves hospitalizations-induced expenses, and possibly prevents permanent visual impairment.
https://www.nature.com/articles/s41598-022-23960-w
