Comparison of MRI findings of hypothalamic-optic chiasmatic gliomas and craniopharyngiomas.

BACKGROUND: Differential diagnosis of hypothalamic-optic chiasmatic gliomas (HOCGs) and craniopharyngiomas on magnetic resonance imaging (MRI) can be quite challenging. PURPOSE: To compare the MRI features of HOCGs and cranipharyngiomas. MATERIAL AND METHODS: Patients diagnosed with HOCG or craniopharyngioma in histopathological evaluation between 2012 and 2022 and who underwent preoperative contrast-enhanced brain MRI were included. Various MRI features were retrospectively evaluated for each lesion: T2-weighted imaging and fluid attenuation inversion recovery hyperintensity, calcification, cystic change, T1-weighted (T1W) imaging hyperintensity of the cystic component, hemorrhage, involvement of sellar, suprasellar or other adjacent structures, lobulated appearance, presence of hydrocephalus, and contrast enhancement pattern. Apparent diffusion coefficient (ADC) values were also evaluated and compared. RESULTS: Among 38 patients included, 13 (34%) had HOCG and 25 (66%) had craniopharyngioma. Craniopharyngiomas had a significantly higher rate of cystic changes, calcification, and T1W imaging hyperintensity of the cystic component than HOCGs (P <0.05). Of HOCGs, 92% had chiasm involvement, 23% had optic nerve involvement, and 31% had brain stem involvement. On the other hand, chiasm involvement was observed in 8% of craniopharyngiomas, but none had optic nerve and/or brain stem involvement (P <0.05). While 62% (8/13) of HOCGs had diffuse homogeneous enhancement, 80% (20/25) of craniopharyngiomas had a diffuse heterogeneous enhancement pattern. Mean ADC values were significantly higher in craniopharyngiomas compared to HOCGs (2.1 vs. 1.6 ×10-3mm2/s, P <0.05). CONCLUSION: Although some neuroimaging findings may overlap, features such as presence of cyst and calcification, brain stem and optic pathway involvement, different enhancement patterns, and ADC values may be helpful in the differential diagnosis of HOCGs and craniopharyngiomas.

The association between calreticulin and glucagon-like peptide-1 expressions with prognostic factors in high-grade gliomas.

OBJECTIVE: The aim of this study is to present the expressions of Calreticulin (CALR) and Glucagon-like peptide-1 (GLP-1) in high-grade gliomas and to further show the relation between the levels of these molecules and Ki-67 index, presence of Isocitrate dehydrogenase (IDH)-1 mutation, and tumor grade. PATIENTS AND METHODS: A total of 43 patients who underwent surgical resection due to high-grade gliomas (HGG) (grades III and IV) were included. The control group comprised 27 people who showed no gross pathology in the brain during the autopsy procedures. Adequately sized tumor samples were removed from each patient during surgery, and cerebral tissues were removed from the control subjects during the autopsy procedures. Each sample was stored at -80°C as rapidly as possible until the enzyme assay. RESULTS: Patients with high-grade gliomas showed significantly higher levels of CALR and significantly lower levels of GLP-1 when compared to control subjects (P = 0.001). CALR levels were significantly higher, GLP-1 levels were significantly lower in grade IV gliomas than those in grade III gliomas (P = 0.001). Gliomas with negative IDH-1 mutations had significantly higher CALR expressions and gliomas with positive IDH-1 mutations showed significantly higher GLP-1 expressions (P = 0.01). A positive correlation between Ki-67 and CALR and a negative correlation between Ki-67 and GLP-1 expressions were observed in grade IV gliomas (P = 0.001). CONCLUSIONS: Our results showed that higher CALR and lower GLP-1 expressions are found in HGGs compared to normal cerebral tissues.

Surgical management of pseudotumor cerebri syndrome: A single center experience with endoscopic optic nerve decompression and CSF diversion procedures.

OBJECTIVES: Pseudotumor cerebri syndrome (PTC) is a chronic disorder, which is initially treated by conservative measures, yet surgery is inevitable in case of progressive worsening of vision or headache despite medical treatment. The surgical management is controversial including CSF diversion procedures and optic decompression. The purpose of this study was to evaluate the efficacy of different surgeries in PTC and to present surgical outcomes in a single center. METHODS: This retrospective study included the patients with PTC who were operated by endoscopic optic nerve decompression (EOND), ventriculoperitoneal (VP) and lumboperitoneal (LP) shunting. Surgical outcomes, i.e. visual acuity, visual field, papilledema and headache were compared according to type of surgery. Surgical complications were noted. RESULTS: Seventeen of 36 patients were treated with shunting, 14 with EOND and 5 patients with both EOND and shunting. No statistical significance was observed between CSF diversion procedures and EOND concerning clinical outcomes. The improvement rate of papilledema was higher with VPS (p = 0574) while more patients benefitted from LPS regarding visual field and acuity (p = 0471 and p = 0718, respectively). The best treatment response for headache was in shunt implemented patients (VPS and LPS) with a rate of 88.2% followed by EOND (78.6%) and both surgeries (60%)(p = 0.294). Gender and BMI were significant predictors of improved papilledema (p = 0.034). CONCLUSIONS: Our study demonstrated comparable results between shunting and EOND, regarding the efficacy on surgical outcomes. EOND is quite effective for headache besides its advantage on treatment-refractory visual loss. Shunting may offer sustained relief of symptoms when compared with EOND.

Tissue Expressions of Regulatory Enzymes of the Krebs Cycle in Low- and High-grade Gliomas.

AIM: To compare tissue levels of the regulatory enzymes related to the Krebs cycle between low, and high-grade supratentorial gliomas. MATERIAL AND METHODS: Forty patients who underwent surgery for supratentorial gliomas (19 with low-grade and 21 with high-grade gliomas) were evaluated. The regulatory enzymes directly involved in the Krebs cycle, namely pyruvate dehydrogenase, citrate synthase, ?-ketoglutarate dehydrogenase, and isocitrate dehydrogenase, and two enzymes that indirectly regulate the Krebs cycle, namely glutamate dehydrogenase and glutaminase, were quantitatively studied in tumor tissues using ELISA. The results were compared between the two groups. RESULTS: The levels of all enzymes were higher in the high-grade glioma group but only pyruvate dehydrogenase, citrate synthase, and isocitrate dehydrogenase levels showed statistical significance. Moreover, all enzymes showed higher tissue levels in grade- II compared to grade-I gliomas, but only two enzymes, glutamate dehydrogenase and glutaminase, reached significantly higher levels. In the high-grade glioma group, all enzymes again showed higher tissue levels in grade-IV gliomas than in grade-III gliomas, but none showed statistical significance. CONCLUSION: Regulatory enzymes of the Krebs cycle are increased in high-grade gliomas compared to low-grade gliomas. Glutaminolysis enzymes, namely glutamate dehydrogenase and glutaminase, which are required for resupplying the Krebs cycle, are also increased in order to meet the high energy demand in high-grade gliomas.

The efficacy of preoperative diffusion tensor tractography on surgical planning and outcomes in patients with intramedullary spinal tumor.

PURPOSE: The aim of this study was to investigate the efficacy of diffusion tensor tractography (DTT) of spinal cord on surgical planning and postoperative neurological outcomes in patients with spinal intramedullary tumors. METHODS: The study was conducted retrospectively from the radiological and clinical data of our hospital database. Patients with intramedullary spinal cord tumors who underwent diffusion tensor imaging for spinal cord lesions were selected between 2019 and 2022. Demographic characteristics and intraoperative neurophysiological monitoring data were evaluated. The McCormick scale was used to grade the pre- and postoperative neurological status of the patients. The tumoral lesions were categorized into 3 types according to the fiber course on DTT. RESULTS: Eleven patients were found to have radiological findings that were compatible with intramedullary tumor; eight (72.7%) of them ultimately underwent surgery following being approved as surgical candidates in the spinal diffusion tensor imaging studies. Six cases had Type 1, one case had Type 2, and 4 cases had Type 3 tumors according to the fiber course. All Type 1 tumors were classified as resectable and all of them were gross totally resected. Type 2 lesion that was rated as resectable by DTI was subtotally resected. Type 3 lesions were followed without surgery except the one with tumoral progression and neurological deficit. The postoperative neurological outcomes were compatible with intraoperative neurophysiological monitoring results. CONCLUSION: Diffusion tensor imaging and tractography may be beneficial regarding the selection of patients suitable for surgery and in the subsequent surgical planning.

Multilevel Cervical Epidural Hematoma After C5-6 Anterior Cervical Discectomy and Fusion: The Cry of a Neurosurgeon.

Anterior cervical discectomy and fusion (ACDF) is a safe and effective surgical treatment for cervical degenerative disk diseases. Almost every neurosurgeon is familiar with this approach. Anterior multilevel epidural hematoma (EDH) after a single ACDF is a very rare complication documented in the literature. There is no common consensus on the choice of optimal surgical treatment. Here, we report the case of a patient who showed multilevel EDH after ACDF at the C5-6 level to highlight that this complication should be kept in mind even after an uneventful surgery.

Endoscopic Endonasal Optic Nerve Decompression in Idiopathic Intracranial Hypertension: When to Implement Optic Nerve Sheath Fenestration.

BACKGROUND AND OBJECTIVE: Idiopathic intracranial hypertension (IIH) is a syndrome characterized with increased intracranial pressure and normal cerebrospinal fluid (CSF) composition. Treatment is mainly conservative, whereas CSF diversion surgery is the most frequently used surgical intervention. Endoscopic endonasal optic nerve decompression (EOND) is a newer surgical treatment of this patient group. This study presents a single clinic's case series with comparative results of unilateral an bilateral EOND with or without optic nerve fenestration. METHODS: Sixteen patients with IIH syndrome who underwent 18 EOND procedures by a single neurosurgeon were evaluated with MRI and digitally subtracted angiography preoperatively. Both preoperative and postoperative visual acuity and perimetry and fundoscopy examinations were routinely performed. All patients underwent sphenoidotomy using the endoscopic binostril approach; however, unilateral or bilateral optic nerve decompression and accompanying optic sheath fenestration was determined on a case-by-case basis, after which all patients were also evaluated for the outcome of headaches. RESULTS: Most of the patients were female, and the mean age was 30.28 ± 9.78 years. CSF pressure was increased in all patients (406.43 ± 112.91 mm of H 2 O), and the follow-up period was 61.72 ± 21.67 months. In patients with unilateral EOND, visual fields improved in 83%, visual acuity in 70%, headache in 75%, and papilledema in 27% of cases. In patients with bilateral EOND, perimetry improved in 86%, visual acuity in 43%, headache in 50%, and papilledema in 57% of cases. CONCLUSION: EOND is an effective surgical option in the treatment of IIH. Bilateral decompression is preferable in patients with bilateral visual involvement, and optic nerve fenestration may prove to be helpful in patients with IIH whose primary complaint is headache.

Tissue and plasma free amino acid detection by LC-MS/MS method in high grade glioma patients.

PURPOSE: The changes in serum amino acid profiles are evaluated in different types of cancers and screening tests were developed for estimating the risk of cancer by rapid analysis of plasma free amino acid (PFAA) levels. There is scarce evidence about the metabolomics analysis of PFAA in malignant gliomas. The aim of the present study was to identify the most promising diagnostic amino acid biomarkers that could be objectively measured for high-grade glioma and to compare their level with the tissue counterpart. METHODS: In this prospective study, we collected serum samples from 22 patients with the pathological diagnosis of high-grade diffuse glioma according to WHO 2016 classification and 22 healthy subjects, and brain tissue from 22 controls. Plasma and tissue amino acid concentrations were analyzed applying liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. RESULTS: Serum alanine, alpha-aminobutyric acid (AABA), lysine (Lys) and cysteine concentrations were significantly higher in high-grade glioma patients despite low levels of alanine and Lys in the tumor tissue. Aspartic acid, histidine and taurine were significantly decreased in both serum and tumors of glioma patients. A positive correlation was detected between tumor volumes and serum levels of latter three amino acids. CONCLUSION: This study demonstrated potential amino acids which may have diagnostic value for high-grade glioma patients by utilizing LC-MS/MS method. Our results are preliminary to compare serum and tissue levels of amino acids in patients with malignant gliomas. The data presented here may provide feature ideas about the metabolic pathways in the pathogenesis of gliomas.

Surgical Outcome of Young and Adult Patients with Temporal Lobe Epilepsy Related to Hippocampal Sclerosis in Modern Era.

AIM: To evaluate the preoperative, operative, and postoperative outcomes of young and adult patients who underwent surgery for temporal lobe epilepsy related to hippocampal sclerosis (TLE-HS). MATERIAL AND METHODS: This retrospective study assessed prospectively registered data collected from 2010 to 2020. Clinical, electrophysiological, pathological, and postoperative outcomes were evaluated and compared. Post-surgical seizure outcome was classified into continuous seizure freeness without aura and relapse. RESULTS: In total, 16 young and 48 adult patients with TLE-HS were included in the analysis. The clinical, electrophysiological, pathological, and postoperative outcomes were similar between the young and adult groups. However, the seizure outcome did not significantly differ between the two groups (p=0.38). A significant proportion of patients in both groups were satisfied with the surgical outcomes. CONCLUSION: Surgery is extremely effective against TLE-HS in young patients, as in adults. Furthermore, the clinical, radiological, and pathological outcomes are similar between young and adult patients with TLE-HS.

What Happens to Serum Levels of Visinin-Like Protein-1, Caveolin-1 and Neuron-Specific Enolase after Supratentorial Glioma Resection: A Pilot Study.

AIM: To observe changes in the serum levels of visinin-like protein-1 (VILIP-1), caveolin-1 (Cav-1) and neuron-specific enolase (NSE) after glioma resection. MATERIAL AND METHODS: Consecutive 14 glioma patients with different histologic grade and 14 age and gender-matched healthy subjects were included in this pilot study. From the patients serum samples were taken in preoperative and on day 2 and 10 of postoperative periods. Healthy subjects provided serum sample once. The serum changes of three proteins were evaluated by ELISA. The results were compared between preoperative and postoperative periods and between patients and controls. RESULTS: Preoperative serum levels of VILIP-1 (p = 0.008) and Cav-1 (p = 0.012) were significantly higher in the patients. Mean serum levels of VILIP-1 (p = 0.002) and Cav-1 (p = 0.013) again were significantly higher than those of the controls. None of the periods NSE did not show significant changes compared to controls. There was a steady decline regarding all three molecules from preoperative to postoperative day 10. However, statistical comparisons did not reveal any significant difference with respect the decline in any molecule. Significant positive correlation was detected between preoperative serum levels of VILIP-1 and CAV-1 (p = 0.00001) in the patients and the controls (p = 0.0000). CONCLUSION: This pilot study suggested that Cav-1 and particularly VILIP-1 may be used as a valuable serum biomarker for follow-up and for early detection of recurrence in high-grade gliomas. Future studies including larger cohort of patients with homogeneous group of glioma is required.

Do we need postoperative antibiotics in supratentorial clean neurosurgery? A prospective, randomized, single-blind, and placebo-controlled study.

BACKGROUND: To assess the efficacy of postoperative antibiotics on postoperative infection in clean supratentorial craniotomies. METHODS: This study is a prospective, randomized, single-blind, and placebo-controlled clinical trial that included consecutive patients who underwent clean supratentorial craniotomy between November 2017 and September 2020 and evaluated the effectiveness of postoperative antibiotic prophylaxis on postoperative infection. RESULTS: A total of 80 patients were included and the whole group was divided into two groups. Group A included patients who received antibiotic prophylaxis and group B who did not receive antibiotic prophylaxis after surgery. Each group included the same number of patients (40 patients in each). Two patients showed postoperative infection, and both were in group B. No significant difference was found regarding postoperative infection between the two groups (p = 0.15). The rate of postoperative infection was found to be 2.5% in the whole group (2 cases out of 80) and it was 5% in group B (2 cases out of 40). DISCUSSION: Our results showed that antibiotic prophylaxis after a clean supratentorial craniotomy has no effect on the prevention of postoperative infection and we do not suggest using antibiotic prophylaxis after clean supratentorial neurosurgery.

Trigeminal neuralgia as a complication after anterior temporal lobectomy: A case report.

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy. Anterior temporal lobectomy (ATL) leading to high rate of seizure freedom is a safe and well-established procedure in TLEs. Cranial nerve deficits, especially for oculomotor, trochlear and facial nerve were reported as a complication after ATL. Nonetheless, trigeminal neuralgia due to ATL is a very rare complication documented in the literature. The surgeons performing ATL procedures must be aware of the risk of trigeminal nerve injury, avoid excessive electrocautery use in the medial part of middle fossa and provide clean surgery in there to prevent this rare complication.

Seizure Outcome in Adult Patients with Supratentorial Cavernomas.

Background Cavernomas are usually found in the supratentorial area, and epileptic seizures are one of the presenting symptoms. Objective This study aims to provide the seizure outcome in adult patients who underwent surgical excision of single supratentorial cavernomas. Materials and Methods A total of 23 patients with single supratentorial cavernomas were operated between May 2011 and January 2019. Pre- and postoperative seizure semiology, clinical, and radiological findings were collected from medical records. At the last follow-up, each patient was seen during regular visits and clinical variables were noted. Results The mean age was 37.08 ± 10.5 years, and 11 (57.8%) and 12 (52.2%) were females and males, respectively. Headache (43.5%) and seizure (43.5%) were the most common presenting symptoms. Cavernomas were located on the right side in 13 and on the left side in 10 patients. The most common locations were the frontal (43.5%) and temporal (43.5%) lobes. The mean follow-up in this series was 41.4 ± 30.8 months. Our results showed that surgery was effective in seizure outcome, as almost 70% of patients who had seizure before surgery was seizure free after surgery, and the difference between those who had seizure pre- and postoperative periods was statistically significant ( p = 0.0001). Conclusion Surgery is safe and effective for supratentorial cavernomas. The excision of cavernoma together with the surrounding hemosiderin should be performed to obtain a satisfactory seizure outcome.

Circulating Levels of Thrombospondin-1 and Thrombospondin-2 in Patients with Common Brain Tumors.

AIM: To measure serum levels of thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2) in patients with common brain tumors, namely high-grade glioma (HGG), low-grade glioma (LGG), and meningioma. MATERIAL AND METHODS: For this prospective study, a total of 56 patients were operated on for supratentorial gliomas and meningiomas, and 18 healthy subjects were evaluated. Serum levels of angiostatic molecules were measured with enzyme-linked immunosorbent assay. The results of patients were compared with those of healthy subjects. RESULTS: High serum levels of TSP-1 were seen in HGG, followed by LGG, meningioma groups, and controls. The only significant difference was found between HGGs and controls (p=0.004). There was a trend to decrease from HGG to controls. High serum levels of TSP-2 were seen in controls, followed by meningioma, LGG, and HGG. None of the patient groups showed significant differences compared with controls. Among the patient groups, TSP-2 was significantly higher in the meningioma group than the HGG group (p=0.01). No correlation was found with any of the molecules and the clinical parameters, including the presence of peritumoral edema or seizure, the anterior-posterior diameter of the tumor, and, more importantly, the grade of glioma. CONCLUSION: Our results indicate that TSP-2 might be more important than TSP-1 in preventing angiogenesis and a major angiostatic factor in glioma cells.

Health-related Quality of Life Assessment in Patients with Malignant Gliomas.

BACKGROUND: High-grade gliomas have limited time of survival despite aggressive treatment. Patients experience a decline in their physical and mental capacities, affecting their quality of life (QoL), and require proper therapeutic strategies. OBJECTIVE: To assess the QoL of malignant glioma patients before and after the treatment in a longitudinal study of six months. METHODS AND MATERIAL: Forty-nine patients who were pathologically diagnosed with glioblastoma and anaplastic glioma according to WHO 2016 were included in this prospective study. The assessment of quality of life was done using the European Organization for Research and Treatment of Cancer (EORTC) quality of life (QoL) questionnaire core-30 prior to surgery, 1 and 5 months after the operation. RESULTS: The decline in Karnofsky scores of the patients was statistically significant. Among the symptom scales, fatigue was more prominent after surgery while pain was noticeable during chemotherapy which was correlated with increased age. The mean overall QoL scores showed a clinically significant decline during the postoperative period. The functional scores demonstrated a significant decline in between all periods. Sex was significantly correlated with preoperative emotional and physical functioning. The patients with right-sided lesions had higher mean scores for social and cognitive functioning. CONCLUSIONS: Low KPS, older age, and female gender may affect cancer symptoms and physical and social activities in malignant glioma patients. Cognitive functions as well as social and occupational roles gradually decline during the first six months of treatments. Overall QoL of high-grade glioma patients deteriorates especially after radiotherapy and during the first months of chemotherapy.

Circulating Levels of Thrombospondin-1 and Thrombospondin-2 in Patients with Temporal Lobe Epilepsy Before and After Surgery.

AIM: To measure the serum levels of strong angiostatic and synaptogenetic molecules thrombospondin-1 (TSP-1) and thrombospondin-2 (TSP-2) in patients with temporal lobe epilepsy (TLE) before and after surgery. MATERIAL AND METHODS: In this prospective study, 20 patients operated for TLE and 20 healthy subjects were included. Serum levels of TSP-1 and TSP-2 were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Our findings showed that both groups had higher serum levels of both molecules "before" surgery than 10 days ?after? SURGERY: However, a significant difference was noted between ?before? and "after" surgery regarding TSP-1 (p=0.00001). Although a marked decrease was found "after" surgery with respect to TSP-2, the difference did not reach statistical significance (p=0.22). In patients with TLE, serum levels of both molecules ?before? surgery were found to be significantly higher than in healthy controls (TSP-1, p=0.00001; TSP-2, p=0.007). CONCLUSION: Serum levels of TSP-1 and TSP-2 are determined to be higher in patients with TLE than in healthy subjects, and the resection of epileptogenic tissues decreases the serum levels of these molecules. Future studies should involve a higher number of patients with serial serum levels of TSP-1 and TSP-2 at the long-term follow-up to correlate with seizure outcome.

Assessing the connectional anatomy of superior and lateral surgical approaches for medial temporal lobe epilepsy.

The most common approaches in the treatment of epilepsy, the trans-sylvian selective amygdalohippocampectomy (SAH) and the anterior temporal lobe resection (ATLR) reach the medial temporal lobe through different surgical routes. Our aim was to delineate the white matter (WM) fiber tracts at risk in relation to trans-sylvian SAH and ATLR by defining each fascicle en route to medial temporal lobe during each approach. ATLR and trans-sylvian SAH were performedand related WM tracts en route to medial temporal region were presented in relation to the relevant approaches and surrounding neurovascular structures. The WM tracts most likely to be disrupted during trans-sylvian SAH along the roof of the temporal horn were the UF - and less commonly IFOF - at the layer of the external capsule, anterior commissure, anterior bend of optic radiations, and sublenticular internal capsule. Amygdaloid projections to the claustrum, putamen and globus pallidus, the tail of caudate and the peduncle of the lentiform nucleus were also in close proximity to the resection cavity. Fiber tracts most likely to be impaired during ATLR included the UF, ILF, IFOF, anterior commissure, optic radiations, and, less likely, the vertical ventral segment of the arcuate fascicle. Both ATLR and trans-sylvian SAH carry the risk of injury to WM pathways, which may result in unpredictable functional loss. A detailed 3-D knowledge of the related connectional anatomy will help subside neurocognitive, neuroophtalmologic, neurolinguistic complications of epilepsy surgery, providing an opportunity to tailor the surgery according to patient's unique connectional and functional anatomy.

Ultrastructural investigation of synaptic alterations in the rat hippocampus after irradiation and hyperthermia.

This study aimed to investigate ultrastructural synaptic alterations in rat hippocampus after in utero exposure to irradiation (IR) and postnatal exposure to hyperthermia (HT). There were four groups in each of the time points (3rd and 6th months). IR group: Pregnant rats were exposed to radiation on the 17th gestational day. HT group: Hyperthermia was applied to the rat pups on the 10th day after their birth. IR+HT group: Both IR and HT were applied at the same time periods. Control group: No IR or HT was applied. Rat pups were sacrificed after 3 and 6 months. Thin sections from the dentate gyrus (DG) and the CA3 of hippocampus were evaluated for synapse numbers by electron microscopy. Synapses were counted, and statistical analysis was performed. Abnormalities in myelin sheath, mossy terminals and neuropil were observed in the CA3 and DG of all groups. The synapses in the CA3 region were significantly increased in the IR-3rd month, IR-6th month, and IR+HT-3rd month groups vs control group. Synapses were significantly increased in the DG of HT-3rd month group. A trend for an increase in synapse numbers was seen in the CA3 and DG. Increased number of synapses in the rat hippocampus may be due to mossy fiber sprouting, possibly caused by in utero irradiation and/or postnatal hyperthermia.