ObjectiveEpilepsy is considered as a network disorder of interacting brain regions. The propagation of local epileptic activity from the seizure onset zone (SOZ) along neuronal networks determines the semiology of seizures. However, in highly interconnected brain regions such as the insula, the association between the SOZ and semiology is blurred necessitating invasive stereoelectroencephalography (SEEG). Normative connectomes on MRI data enable to link different symptoms and lesion locations to a common functional network. The present study applied connectomics to disentangle epilepsy networks from insular SEEG recordings and to describe their relationship to seizure semiology.MethodsWe retrospectively extracted functional networks by normative connectome analysis from 118 insular contacts depicting epileptic discharges during SEEG in 20 epilepsy patients. The resulting epilepsy networks were correlated to the corresponding semiology by voxel-wise regression and multivariate analyses of variances.ResultsEpileptic foci were found in the posterior insula for somatosensory, other sensory and motor seizures, while cognitive and autonomic symptoms were related to the anterior insula. We identified insular connections to the superior temporal gyrus and heschl gyrus in sensory seizures and projections to the somatosensory cortex in somatosensory seizures. Insula-basal ganglia pathways were found in cognitive seizure manifestations, while insular connectivity to fronto-basal regions were strongest in patients with autonomic seizures.ConclusionThe semiology of seizures is mirrored in the functional connectivity of insular epileptic discharges. Combining SEEG and connectomics could provide additional information about seizure propagation within the epilepsy network and might enable new treatment options in the future like deep brain stimulation.

Objective:An intracavernous internal carotid artery constriction or occlusion (ICAc/o) has been considered an extremely rare finding in autoimmune hypophysitis (AiHy). This study aimed to analyse predictive factors for the occurrence of ICAc/o in AiHy. Design:Retrospective analysis of three of our own cases and 16 published cases. Methods:Among 15 surgically treated patients with AiHy, we identified three cases with ICAc/o via time-of-flight magnetic resonance angiography (TOF MRA) or computed tomography angiography (CTA). In addition, 16 published cases with AiHy and ICAc/o were identified via the literature search. Clinical features, treatment, and outcomes were evaluated. Results:TOF MRA revealed complete bilateral ICA occlusion (ICAo) in case 1 and incomplete bilateral ICA constriction (ICAc) in case 2. In the third case, left-sided ICAo was confirmed by CTA. None of our three patients with AiHy complicated by ICAc/o suffered brain infarction or neurological deficits. All three cases exhibited a parasellar T2 dark sign and strong dural enhancement. With our three cases included, seven of 19 published cases (36.8%) showed complete bilateral ICAo. Among these, four presented with ischaemic stroke. Eight of 19 patients (42.1%) presented with cranial nerve palsy. While all patients presented with hypopituitarism, only five had arginine vasopressin (AVP) deficiency. Interestingly, 11 patients had a recurrent course of hypophysitis. Conclusion:ICAc/o caused by AiHy appears to be more frequent than previously reported. Special attention should be paid to the carotid arteries in AiHy because of the potentially deleterious complication of ICAc/o. Cranial nerve palsy, a parasellar T2 dark sign, strong perisellar dural enhancement, and a recurrent course of hypophysitis can be considered warning signs of the occurrence of ICAc/o.

Context Macroprolactinomas not only cause hypogonadism, but also other pituitary dysfunctions, like deficiency of adrenocorticotrophic hormone (ACTH) and thyroid-stimulating hormone (TSH). While dopamine agonist treatment shows varying recovery rates of these insufficiencies, surgical outcomes are less studied, and a direct comparison between treatments is lacking. Objective To evaluate recovery of pituitary dysfunction in medically vs. surgically treated patients with macroprolactinoma. Design Retrospective multicenter study including 104 patients with macroprolactinoma (44 surgically vs. 60 medically treated) with at least two hormonal deficiencies before treatment. Results Before surgery, all patients presented with hypogonadotropic hypogonadism, 25 (57%) with ACTH-deficiency, and 32 (73%) with TSH-deficiency. 10 months post-surgery, prolactin normalized in 25 (57%) patients, while 19(43%), 15 (60%) and 10(31%) recovered from hypogonadism, ACTH-deficiency, and TSH-deficiency, respectively. Before medical therapy, hypogonadism was observed in all patients, ACTH-deficiency in 31 (52%), and TSH-deficiency in 50 (83%). After 12 months under dopamine agonists, prolactin levels normalized in 36 (60%) patients, 25(42%) recovered from hypogonadism, 17 (55%) from ACTH-deficiency, and 14(28%) from TSH-deficiency. No significant difference in recovery rates between surgical and medical treatment for hypogonadism (OR 1.633, p = 0.338), ACTH-deficiency (OR 0.462, p = 0.319), or TSH-deficiency (OR 0.584, p = 0.339) was observed. Large initial tumor size was a significant negative predictor of recovery for all hormone deficiencies (always p < 0.05), while prolactin normalization was a predictor of recovery of hypogonadism ( p < 0.001). Conclusion Both surgical and medical treatment allow for hormonal recovery in patients with macroprolactinoma, with no significant advantage for either approach. Initial tumor size and prolactin-normalization are predictors of recovery outcomes.

Disclosure: Q. Zhang: None. Y. Cai: None. A. Abreu: None. M. Buchfelder: None. B. Yao: None. F. Hanzu: None. Y. Liu: None. J. Thorsteinsdottir: None. Z. Ma: None. J. Flitsch: None. S. Zhang: None. H. Ye: None. J. Honegger: None. R.S. Carroll: None. Z. Zhang: None. U.B. Kaiser: None. M. Reincke: None. M. Theodoropoulou: None. Y. Zhao: None. L. Gustavo Perez-Rivas: None. Background: The recurrence rate of Cushing’s disease (CD) after surgery varies between 5-50%. About 30-60% of CD tumors carry somatic USP8 variants. Prior studies on small cohorts have reported opposite associations between USP8 variants and recurrence. Here, we analyzed USP8 genotype and recurrence risk in a large, international cohort of patients with postoperative remission and long follow-up. Methods: Retrospective analysis across seven neuroendocrine centers from China, Europe, and USA. All patients had USP8 genotype, demographic, clinical, biochemical, and follow-up data. Patients with prior pituitary intervention or bilateral adrenalectomy were excluded. We estimated the recurrence risk with Kaplan-Meier curve, log-rank test, and Cox regression. Results: Among 435 patients (82.8% female; median follow-up 5.61 years), USP8 variants were identified in 195 (44.8%) tumors. Variants were more prevalent in younger (p<0.001) and female (p<0.001) patients and were associated with a lower incidence of cavernous sinus invasion (p=0.021) and reduced post-operative cortisol levels (p=0.004). Of these, 371 initially reached post-op remission, but 71 recurred during follow-up. USP8 variants significantly increased recurrence risk in microadenomas (HR 2.36, p=0.025), while in macroadenomas, no significant association was observed (HR 0.58, p=0.126). Stratification by USP8 genotype and tumor size produced four subgroups. However, due to similar recurrence risks (HR 1.08, p=0.824) and comparable clinical characteristics between USP8 variant microadenomas and macroadenomas, these two variant subgroups were merged into a single category, resulting in three distinct categories: wild-type microadenomas, USP8 variant adenomas, and wild-type macroadenomas, with 5-year cumulative recurrence rates of 6.45%, 12.53%, and 31.16%, respectively. The log-rank test revealed significant differences in recurrence risk among these 3 categories (p<0.001). Further evaluation of postoperative 1-week nadir cortisol levels showed category-specific recurrence risks. For wildtype microadenomas, cortisol levels ≥ 2 µg/dL were associated with increased recurrence risk (HR 7.26, p=0.016). In USP8 variant adenomas, recurrence risk was elevated only at cortisol levels ≥ 5 µg/dL (HR 6.11, p<0.001). Postoperative cortisol levels were not significantly associated with recurrence in wildtype macroadenomas. We further identified additional, varied factors associated with recurrence risk across the three categories. Conclusions:USP8 genotype, combined with tumor size, is associated with different risk of recurrence in CD. This study highlights the heterogeneity of CD recurrence patterns and underscores the importance of considering both tumor size and somatic USP8 genotype to guide follow-up strategies. Presentation: Sunday, July 13, 2025

CONTEXT:Acromegaly is a rare disease caused by excessive growth hormone (GH) secretion, mostly induced by pituitary adenomas. The care of pregnant women with acromegaly is challenging, in part due to existing clinical data being limited and not entirely consistent with regard to potential risks for mother and child.OBJECTIVE:To retrospectively examine data on pregnancy and maternal as well as neonatal outcomes in patients with acromegaly.DESIGN & METHODS:Retrospective data analysis from 47 pregnancies of 31 women treated in centers of the German Acromegaly Registry.RESULTS:87.1% of the studied women underwent transsphenoidal surgery before pregnancy. In 51.1% a combination of dopamine agonists and somatostatin analogs were used before pregnancy. Three women did not receive any therapy for acromegaly. During pregnancy only 6.4% received either somatostatin analogs or dopamine agonists. In total, 70.2% of all documented pregnancies emerged spontaneously. Gestational diabetes was diagnosed in 10.6% and gravid hypertension in 6.4%. Overall, no preterm birth was detected. Indeed, 87% of acromegalic women experienced a delivery without complications.CONCLUSION:Pregnancies in women with acromegaly are possible and the course of pregnancy is in general safe for mother and child both with and without specific treatment for acromegaly. The prevalence of concomitant metabolic diseases such as gestational diabetes is comparable to the prevalence in healthy pregnant women. Nevertheless, larger studies with more data in pregnant patients with acromegaly are needed to provide safe and effective care for pregnant women with this condition.

Patients with acromegaly oftentimes exhibit a reduced physical and psychological health-related quality of life (HRQoL). Maladaptive coping styles are associated with poor HRQoL in a number of diseases and patients with pituitary adenomas in general exhibit less effective coping styles than healthy controls. This study aimed to assess coping strategies in acromegaly patients in order to explore leverage points for the improvement of HRQoL. In this cross-sectional study, we administered self-report surveys for coping strategies and HRQoL (Short Form SF-36, Freiburg questionnaire on coping with illness, FKV-LIS) in patients with acromegaly. These were set into relation with a variety of health variables. About half of the 106 patients (44.3

INTRODUCTION: Although first-line prolactinoma (PL) management typically involves dopamine agonists (DAs), the role of surgery as a primary therapeutic is being reconsidered given the undesirable side effects of long-term DAs. METHODS: Patients surgically treated for PL from January 2017 through December 2020 were identified. Preoperative characteristics and postoperative outcomes were assessed. Multivariate models adjusting for tumor characteristics and surgery complexity identified factors predictive of complications and long-term adverse outcomes. RESULTS: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PLs were macroadenomas. Most PLs were managed microscopically (69.9%) and fewer endoscopically (29.0%). Although 29.8% of patients experienced at least one early postoperative complication, most were minor (39.3%), with less being major complications (4.4%). The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. Based on available data on follow-up, disease remission on long-term follow-up imaging was achieved in 94.8% of cases, and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. Upon multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly prohibitive against long-term endocrinological cure. Knosp classification was highly predictive of residual tumor or PL recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). CONCLUSIONS: Our results evaluate a modern, multicenter, global series of patients treated for PL. This data serves as a benchmark to compare with DAs and demonstrates that surgery offers high rates of remission with low rates of complications and recurrence. It may be reasonable to consider surgery as an alternative to DAs.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

BACKGROUND:Most pituitary adenomas (PAs), also termed pituitary neuroendocrine tumors, are benign in nature and can be treated effectively by surgical resection, medical treatment, and in special cases by radiotherapy. However, invasive growth can be an important feature of a more aggressive behavior and adverse prognosis. The extension of PAs into the cavernous sinus can be categorized according to the Knosp criteria on magnetic resonance imaging (MRI). Comparative analyses of MRI features and intraoperative findings of invasive growth regarding different clinical factors are still scarce. MATERIALS AND METHODS:We performed a retrospective single-center analysis of 764 PAs that were surgically treated between October 2004 and April 2018. Invasive growth was assessed according to the surgical reports and preoperative MRI (Knosp criteria). Clinical data, such as patient age at diagnosis and gender, histopathological adenoma type, and extent of resection, were collected. RESULTS:Invasive features on MRI were seen in 24.4% (Knosp grades 3A-4, 186/764) of the cases. Intraoperatively, invasion was present in 42.4% (324/764). Complete resection was achieved in 80.0% of adenomas and subtotal resection, in 20.1%. By multivariate analysis, invasion according to intraoperative findings was associated with the sparsely granulated corticotroph (SGCA, P = .0026) and sparsely granulated somatotroph (SGSA, P = .0103) adenoma type as well as age (P = .0287). Radiographic invasion according to Knosp grades 3A-4 correlated with age (P = .0098), SGCAs (P = .0005), SGSAs (P = .0351), and gonadotroph adenomas (P = .0478). Both criteria of invasion correlated with subtotal resection (P = .0001, respectively). CONCLUSIONS:Both intraoperative and radiographic signs of invasive growth are high-risk lesions for incomplete extent of resection and occur more frequently in older patients. A particularly high prevalence of invasion can be found in the SGCA and SGSA types. Cavernous sinus invasion is also more common in gonadotroph adenomas. Usage of the Knosp classification is a valuable preoperative estimation tool.

To improve the understanding of adherence as one major factor of disease control in acromegaly patients, we systematically assessed patients’ motivations to adhere to advised follow-up schedules and recommended medication for acromegaly. Cross-sectional, postal questionnaire study on adult patients with acromegaly, operated upon a growth hormone producing pituitary adenoma more than 1 year ago in two tertiary treatment centers. We assessed demographic and clinical characteristics, disease status, adherence to acromegaly medication and/or aftercare, and the five dimensions defined by the World Health Organization influencing adherence. Wherever applicable, we included validated short scales. The answers of 63 patients (33 f, 30 m; mean age 56.1 y) were analyzed. Patients with problems in adherence to aftercare had a significantly lower subjective symptomload than those adherent to aftercare (p = 0.026) and a lower perceived need for treatment (p = 0.045). Patients with adherence problems to medication had a higher subjective symptomload than those without (p = 0.056). They also tended to have shorter consultations, were significantly more often dissatisfied with the duration of their medical consultations (42

Based on recent data, a total number of about 29 000 patients with adrenal insufficiency can be calculated for Germany, and about 1500 fatalities due to adrenal crises have to be expected within the next decade. Management of adrenal crises is still unsatisfactory. The objectives of this study were to establish consensus for diagnostic criteria, prevention strategies, and treatment recommendations for adrenal crises. The study was conducted from January 2022 to April 2023, using Delphi technique. Four rounds of questionnaires were sent to 45 experts, selected by a coordinating group on behalf of the adrenal section of the German Society of Endocrinology. The survey was implemented online using the REDCap web application. Responses were captured anonymously. During the Delphi process the expert panel developed diagnostic criteria to identify patients likely to have an adrenal crisis. Education about adrenal insufficiency among patients as well as non-endocrine medical personnel were regarded as highly important. It was suggested that recommendations for the management of adrenal insufficiency have to be simplified and made widely available. This study provides pragmatic strategies to identify and treat patients prone to adrenal crisis, thereby highlighting the need for an improved management of patients with adrenal insufficiency.

Abstract BACKGROUND In-vitro studies indicate that gliomas with a mutation of the isocitrate dehydrogenase (IDH) increase neuronal excitability of the peritumoral cortex contributing to epileptogenesis in these patients. However, in-vivo evidence is missing. This study evaluates the electric characteristics of the brain-tumor-interface (BTI) relative to the IDH mutation status. MATERIAL AND METHODS To investigate peritumoral cortical excitability (CE), we applied 5258 pulses of transcranial magnetic stimulation (TMS) at the BTI of IDH-mutant (IDH-mt) and IDH-wildtype (IDH-wt) glial tumors in 39 patients. CE was assessed by the resting motor threshold (RMT) and the synchronized electromyographic (EMG) activity (i.e., event-related spectral perturbation, ERSP) after TMS. ERSP values were related to the IDH status, tumor grading, antiepileptic drug intake (AED) and the spatial relationship to the tumor borders. RESULTS There was not significant group difference in RMT. TMS to the BTI triggered an EMG synchronization decreasing linearly with the distance to the functional hotspot. In contrast, IDH-mt gliomas demonstrated an increased cortical output of the peritumoral brain tissue compared to IDH-wt gliomas. This effect was not attributable to AED intake or other histological and molecular characteristics. Notably, cortical hyperexcitability was detectable well beyond the tumor border. CONCLUSION s: This study provides in-vivo evidence of cortical hyperexcitability at the BTI of IDH-mt gliomas which could contribute to the epileptogenesis in these patients.

Background Despite best clinical management, meningioma patients experience tumor recurrence. Efforts have been made to improve the prognostic stratification of meningiomas. Recently, a multi-faceted molecular classification suggested that the marker S100 is associated with a favorable outcome, making a further analysis in a larger cohort interesting. Materials and methods The immunohistochemical staining for S100 was analyzed in 1669 paraffin-embedded meningioma samples. The distribution and association with clinical data and progression-free survival via radiographic tumor recurrence were assessed. Results Of 1669 cases, 218 tumors showed strong S100 expression (13.1%). A significantly higher frequency of S100 positive meningiomas was observed in meningiomas of female patients, tumors with spinal and convexity/falx location, primary tumor surgery, NF2, higher extent of resection, lower WHO CNS grade, adjuvant radiotherapy and recurrence-free tumors during follow-up. Univariate analysis revealed a favorable progression-free survival for meningiomas with S100 expression ( p = 0.0059) but not in the multivariate analysis. Higher S100 frequency was independently associated with female gender ( p = 0.0003), NF2 ( p < 0.0001), tumor location ( p < 0.0001) and lower WHO CNS grade ( p = 0.0133). Conclusions The positive prognostic impact of S100 is mostly attributed to the confounding clinical factors gender, tumor location, NF2 status and WHO CNS grade.

Invasive video‐electroencephalography (iVEEG) is the gold standard for evaluation of refractory temporal lobe epilepsy before second stage resective surgery (SSRS). Traditionally, the presumed seizure onset zone (SOZ) has been covered with subdural electrodes (SDE), a very invasive procedure prone to complications. Temporal stereoelectroencephalography (SEEG) with conventional frame‐based stereotaxy is time‐consuming and impeded by the geometry of the frame. The introduction of robotic assistance promised a simplification of temporal SEEG implantation. However, the efficacy of temporal SEEG in iVEEG remains unclear. The aim of this study was therefore to describe the efficiency and efficacy of SEEG in iVEEG of temporal lobe epilepsy.

Background Diagnosing Cushing's syndrome (CS) is highly complex. As the diagnostic potential of urinary steroid metabolome analysis by gas chromatography-mass spectrometry (GC-MS) in combination with systems biology has not yet been fully exploited, we studied a large cohort of patients with CS.Methods We quantified daily urinary excretion rates of 36 steroid hormone metabolites. Applying cluster analysis, we investigated a control group and 168 patients: 44 with Cushing's disease (CD) (70% female), 18 with unilateral cortisol-producing adrenal adenoma (83% female), 13 with primary bilateral macronodular adrenal hyperplasia (PBMAH) (77% female), and 93 ruled-out CS (73% female).Findings Cluster-Analysis delineated five urinary steroid metabotypes in CS. Metabotypes 1, 2 and 3 revealing average levels of cortisol and adrenal androgen metabolites included patients with exclusion of CS or and healthy controls. Metabotype 4 reflecting moderately elevated cortisol metabolites but decreased DHEA metabolites characterized the patients with unilateral adrenal CS and PBMAH. Metabotype 5 showing strong increases both in cortisol and DHEA metabolites, as well as overloaded enzymes of cortisol inactivation, was characteristic of CD patients. 11-oxygenated androgens were elevated in all patients with CS. The biomarkers THS, F, THF/THE, and (An + Et)/(110-OH-An + 110-OH-Et) correctly classified 97% of patients with CS and 95% of those without CS. An inverse relationship between 11-deoxygenated and 11-oxygenated androgens was typical for the ACTH independent (adrenal) forms of CS with an accuracy of 95%.Interpretation GC-MS based urinary steroid metabotyping allows excellent identification of patients with endogenous CS and differentiation of its subtypes.

IMPORTANCE:Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available. OBJECTIVE:We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas. DESIGN:A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed. SETTING:Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values. RESULTS:Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%. CONCLUSIONS:This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context.

BACKGROUND: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single -institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers. METHODS: Patients surgically treated for pituitary ade-noma from January 2017 through December 2020 were included. RESULTS: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P [ 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P< 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P< 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients. CONCLUSIONS: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches.

OBJECTIVE:We aimed to investigate differences in episodic memory networks between patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis and healthy controls, especially with regards to the parietal memory network (PMN), as well as their relation to neuropsychological memory performance after mesial temporal resection. METHODS:28 healthy subjects as well as 21 patients with TLE (12 left, 9 right) were investigated using a spatial memory fMRI paradigm, which has been shown to activate the PMN. Regions of interest (ROI) were defined based on the results of the second-level analyses and activations within the predefined ROIs were compared across groups and correlated with postoperative verbal and nonverbal memory scores. RESULTS:Healthy subjects showed activations within regions belonging to the dorsal visual stream and the PMN as well as the bilateral parahippocampal place area, the bilateral frontal eye field, and the bilateral middle frontal gyrus. Comparison between groups revealed that TLE patients activated significantly less in the left middle occipital gyrus and the right precuneus. The activation pattern in left TLE patients showed further reductions, mainly in areas belonging to the dorsal visual stream and the PMN within the left hemisphere. Activations within the left superior parietal lobulus, bilateral inferior parietal lobulus, bilateral middle temporal gyrus, left precuneus, left frontal eye field, and left middle frontal gyrus correlated significantly with postoperative verbal memory scores, and activations within the left superior parietal lobulus, left inferior parietal lobulus, left middle temporal gyrus, and left precuneus correlated significantly with higher performance in postoperative nonverbal memory scores. SIGNIFICANCE:The PMN is involved in episodic memory encoding. Higher activations in areas belonging to the PMN and the dorsal visual stream, especially within the left hemisphere, before amygdalohippocampectomy may result in higher postoperative memory scores. PLAIN LANGUAGE SUMMARY:This study aims to investigate the effects of epilepsy due to hippocampal sclerosis, i.e. scarring in the temporal lobe, on memory networks in the brain. We discovered that especially patients with left-sided hippocampal sclerosis show reduced brain activations in visual areas and memory networks within the left hemisphere of the brain during orientation in space. Importantly, higher activations within these areas may result in better memory after epilepsy surgery.