Multidomain Cognitive Impairment in Children With Pseudotumor Cerebri Syndrome

Original Contribution Section Editors: Clare Fraser, MD Susan Mollan, MD Multidomain Cognitive Impairment in Children With Pseudotumor Cerebri Syndrome Muhammad Mahajnah, MD, PhD, Ariel T. Suchi, MD, Hazar Zahakah, MD, Rajech Sharkia, PhD, Shaden R. Shuhaiber, PhD, Isaac Srugo, MD, Jacob Genizi, MD Background: Although prompt and suitable treatment of pseudotumor cerebri syndrome (PTCS) leads to an excellent prognosis and can prevent optic nerve atrophy, adults show long-lasting neurocognitive deficits even with prompt treatment. The purpose of our study was to evaluate cognitive outcomes in pediatric patients with PTCS. Methods: We performed a prospective study on children diagnosed with PTCS and a healthy control group. Children with pre-existing neurological conditions or psychiatric drug use were excluded. Both groups underwent a neurocognitive evaluation, using the NeuroTrax computerized battery of tests. The PTCS group were tested 3 months after the initial diagnosis. Results: We evaluated 82 children (49 females [60%], 6.5– 16 years old, mean age 13.3), including 26 diagnosed with idiopathic PTC and 56 controls. Global cognitive score (P , 0.001), verbal memory (P , 0.001), executive function (P , 0.001), attention (P, 0.003), and information processing speed (P , 0.004) were all significantly lower in the PTCS group. No differences were found between children currently being treated and those whose symptoms had resolved and treatment was stopped. Conclusions: Children with PTCS experience comprehensive cognitive decline that persists after the resolution of the symptoms and treatment. Journal of Neuro-Ophthalmology 2022;42:e93–e98 doi: 10.1097/WNO.0000000000001420 © 2022 by North American Neuro-Ophthalmology Society Child Neurology and Development Center (MM, ATS, HZ, SSR), Hillel-Yaffe Medical Center, Hadera, Israel; Child Neurology Unit (JG), Bnai-Zion Medical Center, Haifa, Israel; Pediatric Department (IS, JG), Bnai-Zion Medical Center, Haifa, Israel; The Ruth and Bruce Rappaport Faculty of Medicine (MM, IS, JG), Technion, Haifa, Israel; The Triangle Regional Research and Development Center (RS), Kfar Qara, Israel; and Beit Berl Academic College (RS), Israel. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). Authors M. Mahajnah and A. T. Suchi made an equal contribution. Address correspondence to Muhammad Mahajnah, MD, Child Neurology and Development Center, Hillel-Yaffe Medical Center, Hadera 38100, Israel; E-mail: [e-mail] Mahajnah et al: J Neuro-Ophthalmol 2022; 42: e93-e98 T he diagnosis criteria for PTC were originally established by Dandy for the adult population. In 2014, Friedman et al (1) published revised criteria for the diagnosis of pseudotumor cerebri syndrome (PTCS), including adjustment for children. The prognosis for patients with PTCS is excellent with prompt and suitable treatment. In particular, prompt treatment can avert blindness by preventing optic nerve atrophy secondary to continuous intracranial hypertension(2). Since the late 1980s, concerns have been raised about the effects of PTCS on cognitive performance in adults. Sørensen et al (3) described intellectual impairment, mostly on verbal tests. Kaplan et al (4) published a case study involving subjective complaints of concentration and memory deficits. A small retrospective study by Kharkar (5) reported impaired function in memory, learning, visual-spatial skills, and language. Yri et al (6), in a prospective case–control study, found cognitive impairment in 31 newly diagnosed patients with PTCS. The same pattern was demonstrated by Zur et al (7). Does PTCS have the same impact on cognitive functions in the pediatric group? To date, no studies have addressed this question. Differences have been found in epidemiology and in clinical symptoms between children and adults with PTCS (4). Regarding the former, children tend to have less headache, vomiting, and diplopia. Regarding the latter, PTCS among adults is most common in women with obesity, whereas Genizi et al (8) found no gender selection and a relatively low rate of obesity in young children (younger than 12 years). However, it remains unclear whether these differences imply that PTCS is a different disease in children compared with adults and whether it might therefore have different effects on children’s cognitive function. The purpose of this study was to evaluate cognitive outcomes in pediatric patients with PTCS. METHODS Subjects Children, diagnosed with PTCS at the departments of pediatric neurology in Hillel Yaffe Medical Center and Bnai e93 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Zion Medical Center, Israel, who presented between January 2015 and December 2019 were eligible for study enrollment. Inclusion criteria were younger than 18 years; cerebrospinal fluid (CSF) opening pressure .280 mmH2O; normal CSF count and chemistry; normal neurological examination (excluding old irrelevant findings); normal state of consciousness; and no evidence of spaceoccupying lesions, hydrocephalus, or sinus vein thrombosis in brain imaging (CT or MRI). Children with pre-existing neurological conditions or psychiatric drug use were excluded. The control group consisted of healthy volunteers recruited specially for our study. They had a normal neurological examination result and no learning disabilities. The study was approved by the local Helsinki Committee. All participants provided a consent form signed by their legal guardians. Testing Procedure All participants underwent a neurocognitive evaluation using the NeuroTrax computerized battery (7,9–11). The PTCS group were tested 3 months after the initial diagnosis to avoid deviation due to hospital admission and the initiation of drugs’ side effects. The NeuroTrax battery was used to test the following cognitive functions: nonverbal memory, executive function, attention, visual-spatial processing, and problem solving. Accuracy, response time, and means and standard deviations of response time were compared with norms for the appropriate age groups. Refer to Table 1 for the full list of NeuroTrax tests used. Each NeuroTrax outcome parameter was normalized and fitted to an average scale (mean: 100, SD: 15) to permit averaging performance across different types of outcome parameters. Normative data consisted of test data stored on the NeuroTrax central server for individuals classified as cognitively healthy in controlled clinical trials conducted at academic centers. Data Analysis Categorical variables are presented as frequencies and percentages, and continuous variables as mean and SDs. Analyses were first conducted to compare the 2 PTCS groups (26 children were found suitable based on the inclusion criteria for PTCS; 12 patients were currently being treated with acetazolamide and another 14 were previously treated; however, currently they were receiving the medication). Demographic and clinical variables were analyzed using the t test for continuous variables and the chi-squared test or Fisher exact test where appropriate for categorical variables. Performance data were analyzed by ANCOVA, adjusting for disease duration. Similar analyses were then performed to compare the PTCS group to the control group. Statistical analyses were performed using SPSS version 23 (IBM). Significance was set at P , 0.05, e94 and adjustment was made for multiple testing where appropriate. RESULTS Forty children aged 8–17 years were diagnosed with idiopathic PTCS at the 2 medical centers during the period January 2015–December2019. Of these, 26 children were found suitable based on the inclusion criteria. All patients with PTCS either were currently being treated (N = 12) or had been treated (N = 14) with acetazolamide (See Supplemental Digital Content, Table E1, http://links.lww. com/WNO/A524). We recruited 56 healthy children, with matched socioeconomic status, to serve as a control group (Table 1). Overall 82 children (49 females [60%], 7.4–16 years old, mean age 13.3) were evaluated. There was no statistically significant difference in demographic between the PTCS and control groups (Table 2). For the patients with PTCS, the mean time from the beginning of the symptoms until the diagnosis was made was 7.6 months (range 0.5–16.5 months). The only difference between the 12 children currently under treatment and the 14 posttreatment patients was that among the former significantly shorter time passed since the beginning of the symptoms (Table 3). Scores for tests comprising the cognitive profile, including global cognitive score (P , 0.001), verbal memory (P , 0.001), executive function (P , 0.001), attention (P, 0.003), and information processing speed (P , 0.004), were significantly lower in the PTCS group patients except for the visual-spatial component which was not significant after the Bonferroni multiple testing correction (Table 4). The PTCS group had statistically significant nonverbal memory total accuracy (unadjusted P , 0.002) compared with the control group. Executive functions were examined through the Stroop interference test. On the level 1 Stroop test, the PTCS group had a significantly higher mean response time (unadjusted P , 0.002) and tended to have lower composite scores (unadjusted P , 0.005). On the level 2 Stroop test, there were no statistically significant differences after multiple testing adjustments. Among the PTCS group, 61.5% had a significantly lower score in verbal memory. In contrast with executive functions and visual-spatial processing, only 26.9% of the PTCS group had a significantly lower score. There was no association between clinical characteristics and cognitive scores. There was no difference in cognitive profile scores, within the PTCS group between those under treatment and those who had completed treatment (Table 4). DISCUSSION Only a few studies have examined cognitive impairments in patients with PTCS, generally in a small group of adults. Mahajnah et al: J Neuro-Ophthalmol 2022; 42: e93-e98 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 1. Raw data cognitive tests by group PTC (N = 26) Orientation test Mean accuracy Go/no-go Accuracy Response time Response time SD Composite score Omission errors Commission errors Commission response time Problem solving Stroop interference 1 Accuracy Response time Response time SD Composite score Stroop interference 2 Accuracy Response time Response time SD Composite score Stroop interference 3 Accuracy Response time Response time SD Composite score Nonverbal memory Total accuracy Catch game Time to make 1st move 1st Move SD Average number of direction changes Total score Average error on missed trials Delayed nonverbal memory Accuracy Staged info processing Accuracy level 1.1 Response time Response time SD Composite score Accuracy level 1.2 Response time Response time SD Composite score Accuracy level 1.3 Response time Response time SD Composite score Accuracy level 2.1 Response time 96.3 ± 5.6 (100; 81–100) 85.9 ± 15.5 466.6 ± 104.9 138.6 ± 122.9 19.57 ± 5.69 1.39 ± 2.67 3.08 ± 3.45 407.2 ± 154.4 (93; 50–100) (447; 300.0–705.2) (106; 48.0–536.9) (20.3; 7.60–30.00) (0; 0–10) (2; 0–11) (356; 270.0–827.8) 50.0 ± 31.3 (44; 4–96) Control (N = 56) P* 96.9 ± 4.2 (100; 80–100) 0.98 83.2 ± 13.9 (87; 56.6–100.0) 500.4 ± 136.5 (460.6; 296.8–738.8) 207.7 ± 183.2 (111; 38.0–536.9) 18.37 ± 6.22 (19.4; 8.64–30.30) 1.28 ± 1.89 (0; 0–5) 4.25 ± 3.57 (3; 0–11) 481.6 ± 213.2 (405.4; 39–908) 68.9 ± 22.9 (76; 8–100) 0.12 0.51 0.45 0.53 0.70 0.06 0.17 0.02 93.1 ± 15.2 856.5 ± 505.9 342.8 ± 309.0 13.86 ± 6.48 (100; 30–100) (699; 336–2,710) (236.5; 63–1,201) (14.4; 2.6–26.8) 96.1 ± 9.0 583.6 ± 222.1 210.9 ± 180.8 18.29 ± 5.57 (100; 50–100) (518; 346–1,276) (139.5; 32–851) (19.0; 7.8–28.2) 0.44 0.002 0.04 0.005 93.5 ± 13.7 801.9 ± 536.2 384.6 ± 367.2 14.58 ± 5.85 (100; 40–100) (663; 332–2,932) (261.0; 64–1,418) (15.0; 2.7–26.0) 95.4 ± 6.2 602.5 ± 265.4 266.4 ± 220.9 18.05 ± 5.76 (100; 73–100) (504; 353–1,694) (187.5; 39–1,081) (18.2; 4.7–28.3) 0.68 0.02 0.24 0.01 64.0 ± 37.9 992.0 ± 678.4 542.0 ± 498.6 10.22 ± 7.82 (73; 0–100) (713; 398–2,584) (290; 26–1,558) (9.7; 0.7–25.1) 72.8 ± 33.5 856.5 ± 527.4 467.6 ± 391.8 12.26 ± 7.49 (87; 0–100) (694; 367–2,132) (318; 50–1,379) (11.7; 0.9–27.2) 0.53 0.39 0.90 0.23 65.6 ± 25.4 (70.5; 16–100) 83.2 ± 15.7 (88.0; 23.7–100.0) 0.002 596.3 ± 162.8 (546; 403–1,023) 182.9 ± 95.4 (146; 74–463) 0.16 ± 0.12 (0.15; 0.00–0.50) 546.0 ± 169.2 (502; 359–1,039) 217.5 ± 177.4 (143; 52–735) 0.19 ± 0.12 (0.20; 0.0–0.55) 0.08 0.73 0.17 703.7 ± 196.3 (760; 92–920) 0.35 ± 0.22 (0.30; 0.10–0.80) 748.6 ± 220.7 (760; 89–1,000) 0.30 ± 0.33 (0.20; 0.00–1.80) 0.28 0.12 67.0 ± 30.4 (75; 13–100) 93.6 ± 14.1 902.0 ± 215.2 252.0 ± 148.2 11.21 ± 3.58 93.6 ± 14.1 714.0 ± 173.8 (100; 50–100) (887; 559–1,339) (205; 55.0–586.7) (11.1; 4.74–17.90) (100; 40–100) (690; 451.0–1,054.8) 174.0 ± 117.4 (164; 42.0–518.5) 13.91 ± 3.86 (14.2; 7.27–22.20) 81.6 ± 17.5 (80; 39–100) 678.1 ± 138.7 (632; 480–947) 169.1 ± 89.6 (144; 59.0–335.3) 13.00 ± 4.01 (13.6; 5.65–20.80) 77.3 ± 23.9 (90; 30–100) 1,536.65 ± 236.85 (1,472.5; 1,206–2063.6) Mahajnah et al: J Neuro-Ophthalmol 2022; 42: e93-e98 83.0 ± 19.8 (88; 25–100) 92.6 ± 13.3 (100; 50–100) 806.0 ± 214.6 (764; 500–1,311) 255.4 ± 154.4 (211; 70.0–666.0) 12.46 ± 3.95 (12.7; 4.74–19.90) 93.3 ± 10.1 (100; 70–100) 697.2 ± 187.9 (660; 421.0–1,094.0) 208.4 ± 133.9 (180; 49.0–550.0) 14.57 ± 4.47 (14.4; 7.27–23.80) 81.7 ± 19.6 (90; 39–100) 624.2 ± 148.4 (587; 410–922) 162.1 ± 84.3 (136.5; 57.0–335.3) 14.31 ± 5.20 (15.0; 5.65–24.40) 82.8 ± 19.2 (90; 30–100) 1,177.26 ± 354.18 (1,094.0; 675–2069) 0.02 0.66 0.07 0.84 0.26 0.43 0.64 0.18 0.58 0.69 0.07 0.81 0.22 0.58 0.001 e95 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution (Continued ) PTC (N = 26) Response time SD Composite score Accuracy level 2.2 Response time Response time SD Composite score Accuracy level 2.3 Response time Response time SD Composite score Accuracy level 3.1 Response time Response time SD Composite score Accuracy level 3.2 Response time Response time SD Composite score Accuracy level 3.3 Response time Response time SD Composite score Visual-spatial processing 468.1 ± 247.6 5.31 ± 1.92 78.7 ± 24.0 1,126.0 ± 260.3 311.6 ± 123.8 7.75 ± 3.13 38.6 ± 25.7 895.4 ± 238.8 265.9 ± 132.3 5.47 ± 3.58 66.4 ± 21.9 1,624.2 ± 235.9 575.4 ± 239.8 4.22 ± 1.46 41.4 ± 21.9 1,402.9 ± 312.5 489.7 ± 232.6 3.70 ± 1.97 27.2 ± 16.9 1,125.4 ± 249.3 457.9 ± 201.1 3.55 ± 3.29 62.5 ± 23.9 (410; 103–1,219) (5.4; 1.84–8.30) (90; 33.6–100.0) (1,078; 739–1,540.3) (294; 134–515.1) (8.1; 2.57–12.70) (30; 10–100) (850; 534–1,221.2) (291; 40–426.6) (4.2; 2.23–13.80) (70; 20–100) (1,646; 1,233–2006.0) (548.5; 240–1,133) (4.1; 1.20–6.50) (40; 20–100) (1,467; 959–1870.7) (583; 86–743) (3.0; 2.00–8.10) (20; 18.5–70.0) (1,232.6; 464–1,275.1) (468.7; 83–651.5) (2.1; 2.13–15.10) (63; 19–100) Control (N = 56) P* 344.4 ± 168.9 (301; 122–829.3) 7.77 ± 2.83 (8.4; 1.84–13.30) 81.6 ± 22.5 (90; 33.6–100.0) 1,019.1 ± 289.6 (929; 645–1,540.3) 300.2 ± 129.5 (255; 114–515.1) 9.04 ± 3.62 (9.4; 2.57–15.50) 62.2 ± 30.2 (70; 10–100) 804.3 ± 210.2 (763.5; 428–1,232.0) 204.8 ± 96.1 (184; 61–363.5) 8.91 ± 4.38 (9.4; 1.60–16.40) 79.4 ± 20.0 (80; 20–100) 1,264.9 ± 341.3 (1,245; 680–1969.8) 418.1 ± 191.1 (361; 166–977.3) 6.93 ± 2.73 (7.3; 1.20–13.20) 62.4 ± 26.4 (70; 20–100) 1,131.3 ± 280.4 (1,091; 213–1,603) 397.4 ± 182.3 (321; 129–724) 6.16 ± 2.70 (6.6; 1.50–11.40) 38.0 ± 20.0 (30; 20–70) 994.0 ± 269.3 (1,176; 428–1,235) 312.2 ± 162.8 (403; 32–468.7) 4.80 ± 2.95 (4.3; 2.10–11.00) 68.7 ± 14.0 (69; 38–94) 0.02 0.001 0.87 0.08 0.66 0.10 0.004 0.14 0.06 0.004 0.008 0.001 0.005 0.001 0.002 0.001 0.08 0.001 0.001 0.003 0.002 0.50 0.33 Data are mean ± SD (median; range). *Unadjusted P values. Most have found some cognitive impairment in adults with PTCS. Our study is the first to examine cognitive functions in children and adolescents with PTCS. Our findings, for the most part, align with previous findings in adults, with deficits observed in at least some of the sample in all areas of cognitive function. The most dramatic deficits were found in verbal memory, where nearly two-thirds of the PTCS group scored below the SD (Table 4). These findings are in line with those of Arseni et al (12) and Kharkar et al (5) and also with the pivotal study of Sørensen et al (3), who reported verbal deficits in all their patients. On the other hand, Zur et al (7) reported that memory was the only domain unaffected among patients with PTCS. Nearly one-third of the PTCS group achieved a low score processing speed. Yri et al (6) reported the most severe deficits in adults with PTCS in the domains of reaction time and processing speed. The same was reported by Sørensen et al (4) and Zur et al (7). Kharkar et al (5), in a study of 10 patients with PTCS, reported that visual-spatial skills were impaired in 3 patients, executive skills in one patient, and language skills in one patient. Our study in children, likewise, found impairments in visual-spatial skills and executive function, as well as attention. TABLE 2. Demographic and clinical characteristics by group Gender Male Female Age at testing Education Elementary (1–8) High school (9–12) Left handed Computer usage Daily Every few days Weekly or less often e96 All PTC (N = 26) Control (N = 56) 8 (30.8) 18 (69.2) 13.3 ± 2.9 (7.4–17.9) 25 (44.6) 31 (55.4) 13.0 ± 3.8 (7.9–17.9) 12 (46.1) 14 (53.9) 2 (7.4) 39 (69.6) 17 (30.4) 2 (3.6) 13 (48.1) 11 (40.7) 3 (11.2) 37 (66.1) 10 (17.9) 9 (16.0) P 0.23 0.73 0.29 0.42 0.08 Mahajnah et al: J Neuro-Ophthalmol 2022; 42: e93-e98 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution TABLE 3. Demographic and clinical characteristics of the study group Posttreatment (N = 14) All (N = 26) Gender Male Female Age at testing Education Elementary (1–8) High school (9–12) BMI Age at diagnosis Time from diagnosis (months; median, range) CFS pressure Receiving Treatment (N = 12) P 0.79 8 (30.8) 18 (69.2) 13.3 ± 2.9 (7.4–17.9) 4 (28.6) 10 (71.4) 14.1 ± 2.6 (9.7–17.9) 4 (33.3) 8 (67.7) 12.2 ± 3.1 (7.4–16.4) 12 (46.1) 14 (53.9) 23.24 ± 5.93 (14.90–36.10) 12.1 ± 2.8 (6.5–16.0) 7.6 ± 5.8 (5.5; 0.5–16.0) 36.40 ± 9.75 (22–55) 6 (42.9) 8 (57.1) 23.87 ± 5.35 (15.60–33.79) 12.4 ± 2.5 (8.0–16.0) 11.5 ± 5.5 (12.8; 4.5–23.0) 38.75 ± 10.25 (25–55) 6 (50.0) 6 (50.0) 22.43 ± 6.78 (14.90–36.10) 11.8 ± 3.2 (6.5–16.0) 4.3 ± 3.8 (3.1; 0.5–16.0) 34.39 ± 9.21 (22–51) 0.11 0.72 What is the cause of cognitive impairment in PTCS? One possible culprit is the headaches typically suffered by patients with PTCS. Headaches might affect cognitive functioning in various ways. First, the headache itself might cause cognitive decline. Collins et al (13) showed that postconcussion headaches reduced neurocognitive functioning, with more severe headaches associated with worse neurocognitive status. Headache as a cause of cognitive decline has also been demonstrated in migraine. Huang et al (14) found that cognitive performance decreases during migraine, and cognitive dysfunction can be related to the duration and frequency of a migraine attack. Alternatively, the underlying mechanism may be patients’ emotional state. Hodges and Spielberger (15) and Hendler (16) both found that pain can precipitate clinical depression, and Jamison (17) found that patients with chronic pain tend to have difficulties with concentration and memory. Similarly, Keefe et al (18) found that depression can predict pain and pain behavior. Cognitive decline in patients with PTCS might also derive from either the disease itself or the drug treatment. PTCS could cause cognitive decline through gray or white matter dysfunction due to mechanical compression, as in normal pressure hydrocephalus (19), or through the release of cytotoxic substances (20). Previous studies on adults with 0.56 0.58 0.001 0.26 PTCS have tried to identify some answers to this question. Yri et al (6) first evaluated patients with PTCS within seven days of diagnosis, and then reevaluated them a second time after 3 months of treatment. Attention scores and visualspatial memory improved at follow-up, but the other cognitive parameters remained unchanged, and the improvement was largely explained by the test–retest effect. Zur et al (7) found no relationship between cognitive decline and either time from the beginning of the symptoms or acetazolamide treatment. They interpreted this finding as implying that PTCS itself may cause cognitive impairment and speculated that elevated intracranial pressure may cause diffuse effects in a broad array of brain areas. Our findings may support this conjecture. We evaluated patients with PTCS, some during the acute illness and some after total resolution, and no difference was found between those groups in measures of cognitive decline. The similar decline in cognitive function in children and adults with PTCS is somewhat surprising, given the differences between the 2 in both clinical presentation and incidence. First, as noted earlier, children with PTCS tend to suffer less from headache, vomiting, and diplopia. Second, the incidence in children differs from that in adults, with only the latter showing a link between gender (greater prevalence in women) and obesity (8). These differences TABLE 4. Cognitive profile of PTCS group PTCS (N = 26) Global cognitive score Verbal memory Executive function Visual-spatial Attention Information processing speed 87.9 79.3 88.9 91.6 90.9 89.9 ± ± ± ± ± ± 11.2 19.1 10.9 20.3 14.3 14.7 (70.9–107.0) (44.3–112.5) (62.6–103.7) (29.2–120.6) (61.2–110.6) (64.6–126.1) P* # Below SD 0.001 0.001 0.001 0.045 0.003 0.004 11 (42.3%) 16 (61.5%) 7 (26.9%) 7 (26.9%) 9 (34.5%) 7/22 (31.8%) *Unadjusted. Multiple test significance is P , 0.008. Mahajnah et al: J Neuro-Ophthalmol 2022; 42: e93-e98 e97 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution raise the question of whether PTCS has the same pathophysiological mechanism among children and adults. Our findings showing very similar cognitive dysfunction in children compared with adults provide support for the idea that PTCS is the same disease in children and adults, with slightly different expression. CONCLUSIONS Our study revealed that children with PTCS suffer comprehensive cognitive decline that persists after the resolution of symptoms. The findings resemble those found with adult patients. The exact mechanism underlying this decline is still not clear, and further research is needed. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. Mahajnah, A. T. Suchi, H. Zahakah, and J. Genizi; b. Acquisition of data: M. Mahajnah, A. T. Suchi, H. Zahakah, S. S. Rizik, and J. Genizi; c. Analysis and interpretation of data: M. Mahajnah, A. T. Suchi, H. Zahakah, R. Sharkia, I. Srugo, and J. Genizi. Category 2: a. Drafting the manuscript: M. Mahajnah, A. T. Suchi, H. Zahakah, R. Sharkia, and J. Genizi; b. Revising it for intellectual content: M. Mahajnah, A. T. Suchi, H. Zahakah, R. Sharkia, S. S. Rizik, I. Srugo, and J Genizi. Category 3: a. Final approval of the completed manuscript: M. Mahajnah, A. T. Suchi, H. Zahakah, Rajech Sharkia, S. S. Rizik, I. Srugo, and J. Genizi. 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