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Assessment of Neuropsychiatric Indicators in Children and Adolescents With Primary Brain Tumors and Other Brain Space-Occupying Lesions Before and After Surgery

Objectives Cognitive abilities might be impaired due to brain lesions in children and adolescents. This study aimed to investigate neuropsychiatric indicators in children and adolescents with primary brain tumors and other brain space-occupying lesions (SOLs) before and after the surgical procedure. Materials & Methods The current pre-post study was conducted on 81 patients with brain SOLs aged under 18 years hospitalized in the Neurosurgery Ward of Imam Reza university hospital, Tabriz, Iran, within 20 December 2016 to 20 December 2017. The patients with metastatic brain tumors were excluded. Before and after the surgical procedure, Digit Span forward and backward task (to assess working memory), Stroop Task and Trail Making Task A and B (to assess attention), and Rey-Osterrieth Complex Figure Test (ROCF) (to assess visuospatial memory) were carried out. Then, the scores of the tests were compared to standard values and postsurgical scores. Results The most prevalent type of brain SOLs was medulloblastoma, and the most prevalent region of involvement was the posterior fossa. The scores of all tests after the surgery were significantly improved, compared to those before the surgery (P<0.05). In the assessment of Digit Span forward and backward task scores, there was no significant difference between the scores of patients before the surgery and standard values (P>0.05). Regarding the scores of various stages of the ROCF, the scores of the immediate recall stage were significantly low (P<0.05). Regarding Trail Making Task A and B and Stroop Task before the surgery, only Trail Making Task A and B scores were significantly increased (P<0.05). The scores of Trail Making Task A were significantly higher in patients with medulloblastoma and anatomically in left temporal tumors, which indicated greater damage to the attention field (P<0.05). In addition, in cerebellar tumors, the scores of the immediate recall stage of the ROCF were significantly lower than in other brain tumors or SOLs (P<0.05). Conclusion The visuospatial memory and attention of preoperative assessments were significantly impaired, compared to those of the healthy population (P<0.05). Working memory, visuospatial memory, and attention showed improvement, compared to those before the surgery. Deficits in the attention domain were greater in medulloblastoma.


Introduction
Brain tumors are the most common spaceoccupying lesions (SOLs) and simultaneously are the second most prevalent malignancy in children after leukemia (1,2). Various brain tumors have wide differences in invasion and growth (3).
Tumors of pediatrics are different from adults in various aspects in terms of the region and type of tumors. More than 50% of pediatric tumors are infratentorial; however, in adults, pediatric tumors are mostly supratentorial and about 25-30% infratentorial. In addition, most adult tumors are astrocytoma; nevertheless, about 40% of brain tumors among children are undifferentiated tumors (4,5). The tumor complications have two general and regional aspects. General complications are mostly related to the increase in intracranial pressure, which is caused by tumor growth in a limited space. Regional complications indicate the brain regions which are near the tumors (5).
Due to the increase in life expectancy in patients, attentions are focused on various factors that affect brain tumors and improvement in the quality of life (4,6). Patients might suffer from psychiatric problems, cognitive impairments, and physical illness (7,8). Cognitive abilities are investigated through neuropsychological assessment and could be considered a baseline level compared to the conditions after an intervention. These abilities include attention, memory, executive functions, and visuospatial and linguistic capabilities (9). Brain tumors might reversely affect the neuropsychological functioning of the brain (10).
There are several methods for the assessment of neuropsychological ability, such as Trail Making Task A and B (11), Stroop Task (12), Rey-Osterrieth Iran J Child Neurol. Summer 2022 Vol. 16 No. 3 Complex Figure Test (ROCF) (13), and Digit Span forward and backward task (14).

Neuropsychological deficits have a negative
effect on the quality of life of patients with brain tumors. Obtaining accurate information about the neuropsychological functioning level of patients is essential for planning the future supportive and rehabilitation measures (10). It is very important for patients to regain their premorbid functioning abilities; however, even subthreshold degrees of neuropsychological disorders might prevent this aim (15). It has been revealed that cognitive functioning is associated with the prognosis and risk of relapse, in which the potential for relapse is more precisely predicted, compared to imaging techniques (10). The current study aimed to investigate neuropsychological functioning in patients with brain tumors or other SOLs of the brain, referring to a neurosurgery clinic before and after the surgery. Additionally, this study examined the relationship between neuropsychological deficits with the anatomical location and the type of tumor histopathology.

Materials &Methods
This study was performed to explore neuropsychological deficits in patients with primary brain tumors and other brain SOLs before and after the surgery at Imam Reza hospital in Tabriz, Iran. A total of 81 children and adolescents entered the study by considering inclusion and exclusion criteria. The inclusion criteria were age under 18 years, diagnosis of primary brain tumors or other brain SOLs in the Neurosurgery Clinic of Imam Reza university hospital candidate for brain surgery, diagnosis time less than 6 months, the willingness of the patient, parents, or caregivers to participate in the study, passing at least 1 month to enter the assessment after the surgery, and lack of major complications after the surgery based on physician's diagnosis. The exclusion criteria were metastatic brain tumors, use of anticonvulsant and corticosteroid medications, concomitant physical disease, psychiatric treatments, and intelligence quotient (IQ) below 75 prior to the surgery.

Procedure
The present study was approved by the Regional One month after the surgery, the IQ tests and neuropsychological tests were repeated, and the results were compared to those before the surgery.
Neuroimaging reports were studied through medical files to determine the sites of tumors. After the surgery, the precise location of brain SOLs was recorded based on the surgeon's report. In addition, the type of histopathology of the brain SOLs was determined based on the pathologist's report. The existence of any possible relationship between neuropsychological deficits with the anatomical site and the type of histopathology was examined. of this test, the subject is requested to draw from 1 to 12 and A to L such that a periodic pathway would form between the numbers and letters, and again the time is recorded. In Canada, a study was performed to obtain the normal scores of this test in the healthy population in 2004; therefore, the average scores were obtained for every age group (17).

Rey-Osterrieth Complex Figure Test: It is a
neuropsychological assessment in which the subject is asked to copy from a shape with a series of complex lines at first. In the next steps, the subject will be asked to use his/her memory to recover it and draw the shape again (18). This test is used to measure visuospatial memory with three stages, namely copying, immediate recall (re-drawing the shape after 3 minutes), and delayed recall (re-drawing the same shape after 30 minutes). Each stage is scored based on the shape drawn. Moreover, the time of the copying stage is recorded. Palmo et al. (2013) conducted the ROCF on 179 healthy individuals in different age groups.
The goal was to normalize the scores related to this test (19). Task (20).

Digit Span Forward and Backward
Stroop Task: It is used to measure the ability of the subject to inhibit the dominant response. The dominant response inhibition is a process that inhibits the generation of immediate responses that are irrelevant to the task. In the first stage, the subject is asked to quickly read the words "red, green, blue, and yellow" printed in black. The second stage is divergence conditions, whereby, for example, the word "red" is written in green, and the subject is requested to name the word color and not read the word itself (e.g., the correct response is green). At every stage, the number of errors and duration of response are recorded. The of mean scores was carried out through the t-test.
The One-sample runs test was used to investigate the relationship between the neuropsychological indicators with the pathology and anatomical location of tumors. The data were analyzed by SPSS software (version 23). In this study, a p-value less than 0.05 was considered statistically significant.

Results
In this study, 81 eligible children and adolescents hospitalized due to primary brain tumors or brain SOLs at Imam Reza hospital in Tabriz in 2017 were enrolled in the study. The mean age value of the patients was 11.67±3.95 years (range: 6-18 years) ( Figure 1). There was no significant difference between the age groups of children and adolescents and the number of patients with brain lesions (P>0.05).
The One-sample runs test was used to compare the scores of the neuropsychological indicators in patients with brain SOLs before the surgery to standard criteria ( Neuroimaging reports were studied through medical files to determine the sites of tumors.
After the surgery, the precise sites of the tumors were recorded based on the surgeon's report. Table   2 shows the frequency of anatomical locations of brain SOLs in patients. The most prevalent involved region of brain SOLs was the posterior fossa.
Furthermore, the presence of any relationship between cognitive deficits and anatomical site of the brain SOLs was examined. No significant relationship was observed between forward and backward Digit Span tasks, Trail Making Task B, and ROCF copy score, copy time, and delayed recall with the anatomical site of brain SOLs (P>0.05). Trail Making Task A scores in patients with left temporal tumors were significantly higher than in other brain sites (P<0.05; Table 3). In addition, the score of ROCF immediate recall in patients with cerebellar tumors was significantly lower than in other brain tumors or sites (P<0.05).
This study also investigated the association    Table 2 shows the frequency of the histopathological type of brain SOLs in patients. The most common brain SOLs was medulloblastoma (37%).

In Conclusion
The severity and nature of neurocognitive

Acknowledgment
The present study was approved by the Regional