Comparison between MRI-negative and positive results and the predictors for a poor prognosis in patients with idiopathic acute transverse myelitis.

BACKGROUND: Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported. OBJECTIVES: The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis. METHODS: We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models. RESULTS: Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result. CONCLUSIONS: Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.

Alterations of apparent diffusion coefficient from ultra high b-values in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy.

OBJECTIVE: Subcortical nuclei such as the thalamus and striatum have been shown to be related to seizure modulation and termination, especially in drug-resistant epilepsy. Enhance diffusion-weighted imaging (eDWI) technique and tri-component model have been used in previous studies to calculate apparent diffusion coefficient from ultra high b-values (ADCuh). This study aimed to explore the alterations of ADCuh in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy. METHODS: Twenty-nine patients with MRI-negative drug-resistant epilepsy and 18 healthy controls underwent eDWI scan with 15 b-values (0-5000 s/mm2). The eDWI parameters including standard ADC (ADCst), pure water diffusion (D), and ADCuh were calculated from the 15 b-values. Regions-of-interest (ROIs) analyses were conducted in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus. ADCst, D, and ADCuh values were compared between the MRI-negative drug-resistant epilepsy patients and controls using multivariate generalized linear models. Inter-rater reliability was assessed using the intra-class correlation coefficient (ICC) and Bland-Altman (BA) analysis. False discovery rate (FDR) method was applied for multiple comparisons correction. RESULTS: ADCuh values in the bilateral thalamus, caudate nucleus, putamen, and globus pallidus in MRI-negative drug-resistant epilepsy were significantly higher than those in the healthy control subjects (all p < 0.05, FDR corrected). SIGNIFICANCE: The alterations of the ADCuh values in the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy might reflect abnormal membrane water permeability in MRI-negative drug-resistant epilepsy. ADCuh might be a sensitive measurement for evaluating subcortical nuclei-related brain damage in epilepsy patients. PLAIN LANGUAGE SUMMARY: This study aimed to explore the alterations of apparent diffusion coefficient calculated from ultra high b-values (ADCuh) in the subcortical nuclei such as the bilateral thalamus and striatum in MRI-negative drug-resistant epilepsy. The bilateral thalamus and striatum showed higher ADCuh in epilepsy patients than healthy controls. These findings may add new evidences of subcortical nuclei abnormalities related to water and ion hemostasis in epilepsy patients, which might help to elucidate the underlying epileptic neuropathophysiological mechanisms and facilitate the exploration of therapeutic targets.

The value of ictal scalp EEG in focal epilepsies surgery: a retrospective analysis.

OBJECTIVE: To describe the association between preoperative ictal scalp electroencephalogram (EEG) results and surgical outcomes in patients with focal epilepsies. METHODS: The data of consecutive patients with focal epilepsies who received surgical treatments at our center from January 2012 to December 2021 were retrospectively analyzed. RESULTS: Our data showed that 44.2% (322/729) of patients had ictal EEG recorded on video EEG monitoring during preoperative evaluation, of which 60.6% (195/322) had a concordant ictal EEG results. No significant difference of surgery outcomes between patients with and without ictal EEG was discovered. Among MRI-negative patients, those with concordant ictal EEG had a significantly better outcome than those without ictal EEG (75.7% vs. 43.8%, p = 0.024). Further logistic regression analysis showed that concordant ictal EEG was an independent predictor for a favorable outcome (OR = 4.430, 95%CI 1.175-16.694, p = 0.028). Among MRI-positive patients, those with extra-temporal lesions and discordant ictal EEG results had a worse outcome compared to those without an ictal EEG result (44.7% vs. 68.8%, p = 0.005). Further logistic regression analysis showed that discordant ictal EEG was an independent predictor of worse outcome (OR = 0.387, 95%CI 0.186-0.807, p = 0.011) in these patients. Furthermore, our data indicated that the number of seizures was not associated with the concordance rates of the ictal EEG, nor the surgical outcomes. CONCLUSIONS: The value of ictal scalp EEG for epilepsy surgery varies widely among patients. A concordant ictal EEG predicts a good surgical outcome in MRI-negative patients, whereas a discordant ictal EEG predicts a poor postoperative outcome in lesional extratemporal lobe epilepsy.

Insomnia in patients with MRI-negative epilepsy: The associated factors and 3D-pCASL cerebral blood flow perfusion changes.

OBJECTIVE: This study aimed to identify the factors associated with insomnia in MRI-negative epilepsy and uncover the underlying pathological mechanism driving insomnia within the context of epilepsy. METHODS: We conducted a retrospective study of patients with MRI-negative epilepsy recruited consecutively from December 2021 to December 2022. All subjects completed the Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). Additionally, some subjects underwent the three-dimensional pseudo continuous arterial spin labeling(3D-pCASL) imaging examination. Bilateral frontal lobe, temporal lobe, hippocampus, thalamus, amygdala, caudate nucleus and lenticular nucleus were selected as regions of interest(ROI) and cerebral blood flow(CBF) values were measured in these regions. Subjects were classified into insomnia (ISI ≥ 10) or non-insomnia (ISI < 10) groups, and univariate and stepwise logistic regression analyses were employed to identify the factors associated with insomnia. Furthermore, CBF values in each ROI were compared between the two groups to identify the brain regions potentially related to the underlying pathological mechanism of insomnia in epilepsy. RESULTS: A total of 73 patients with MRI-negative epilepsy were recruited in this study(men, 49.3 %). Among them, 14 patients(19.2 %) had insomnia. Univariate regression revealed that nocturnal seizures, number of anti-seizure medication(ASM), anxiety, use of valproic acid(VPA), depression, and excessive daytime sleepiness(EDS) may be associated with insomnia in MRI-negative epilepsy (all p＜0.05). Stepwise regression demonstrated that nocturnal seizures, anxiety, and EDS were independently associated with insomnia in MRI-negative epilepsy (OR[95 %CI]P: 14.64[2.02-106.27]0.008,49.35[3.06-796.61]0.006, 13.28[1.25-140.66]0.032, respectively). Furthermore, CBF values in the left amygdala were significantly lower in patients with MRI- negative epilepsy who had insomnia. CONCLUSION: The prevalence of insomnia in MRI-negative epilepsy is 19.2%. Nocturnal seizures, anxiety, and EDS were independently associated with insomnia in MRI-negative epilepsy. The noteworthy decrease in CBF values in the left amygdala might be connected to the underlying pathological mechanism of insomnia in epilepsy.

Genetic testing, another important tool in presurgical evaluation of focal epilepsies in childhood.

Epilepsy surgery may be a curative therapy for patients with drug-resistant epilepsies when focal lesions or foci are identified. Genetic testing is not yet routinely included in many presurgical evaluation programs although recent evidence support that finding a germline genetic mutation could help to better delineate the patient candidacy to surgery and provide valuable information on the expected surgery outcome. In this study, we report nine patients presenting drug-resistant focal epilepsy enrolled in presurgical evaluation. We show how the identification of genetic pathogenic variant in epilepsy known genes led to the interruption of the presurgical work-up and ruled out surgery in 7 of them. We observed that the co-existence of some recurrent clinical characteristics as early seizures' onset, frequent precipitating factors including fever, and developmental delay or intellectual disability may be useful markers for germline genetic pathogenic variants. In this group, genetic assessment should be mandatory during presurgical work up, mainly in patients with negative magnetic resonance imaging (MRI) or doubtful structural lesions. The integration of next generation targeted sequencing into the presurgical evaluation can improve the selection of candidates for resective surgery and fosters a personalized medicine approach with a better outcome. PLAINE LANGUAGE ABSTRACT: Genetic testing is not yet systematically included in the pre-surgical assessment of patients with drug-resistant focal epilepsies. In this study, through the description of nine patients, we underline how the integration of genomics into the presurgical work up can help in evaluating the patient candidacy to surgery and provide valuable information on expected surgery outcome.

Predictors of seizure outcomes in stereo-electroencephalography-guided radio-frequency thermocoagulation for MRI-negative epilepsy.

Background: One-third of intractable epilepsy patients have no visually identifiable focus for neurosurgery based on imaging tests [magnetic resonance imaging (MRI)-negative cases]. Stereo-electroencephalography-guided radio-frequency thermocoagulation (SEEG-guided RF-TC) is utilized in the clinical treatment of epilepsy to lower the incidence of complications post-open surgery. Objective: This study aimed to identify prognostic factors and long-term seizure outcomes in SEEG-guided RF-TC for patients with MRI-negative epilepsy. Design: This was a single-center retrospective cohort study. Methods: We included 30 patients who had undergone SEEG-guided RF-TC at Sanbo Brain Hospital, Capital Medical University, from April 2015 to December 2019. The probability of remaining seizure-free and the plotted survival curves were analyzed. Prognostic factors were analyzed using log-rank tests in univariate analysis and the Cox regression model in multivariate analysis. Results: With a mean time of 31.07 ± 2.64 months (median 30.00, interquartile range: 18.00-40.00 months), 11 out of 30 patients (36.7%) were classified as International League Against Epilepsy class 1 in the last follow-up. The mean time of remaining seizure-free was 21.33 ± 4.55 months [95% confidence interval (CI) 12.41-30.25], and the median time was 3.00 ± 0.54 months (95% CI 1.94-4.06). Despite falling in the initial year, the probability of remaining seizure-free gradually stabilizes in the subsequent years. The patients were more likely to obtain seizure freedom when the epileptogenic zone was located in the insular lobe or with one focus on the limbic system (p = 0.034, hazard ratio 5.019, 95% CI 1.125-22.387). Conclusion: Our findings may be applied to guide individualized surgical interventions and help clinicians make better decisions.

Morphometric magnetic resonance imaging (MRI) postprocessing in MRI-negative patients with first unprovoked seizure.

OBJECTIVE: The aim of the study was to evaluate the benefits of morphometric magnetic resonance imaging (MRI) postprocessing in patients presenting with a first seizure and negative MRI results and to investigate these findings in the context of the clinical and electroencephalographic data, seizure recurrence rates, and epilepsy diagnosis in these patients. METHODS: We retrospectively reviewed 97 MRI scans of patients with first unprovoked epileptic seizure and no evidence of epileptogenic lesion on clinical routine MRI. Morphometric Analysis Program (MAP; v2018), automated postprocessing software, was used to identify subtle, potentially epileptogenic lesions in the three-dimensional T1-weighted MRI data. The resulting probability maps were examined together with the conventional MRI images by a reviewer who remained blinded to the patients' clinical and electroencephalographical data. Clinical data were prospectively collected between February 2018 and May 2023. RESULTS: Among the apparently MRI-negative patients, a total of 18 of 97 (18.6%) showed cortical changes suggestive of focal cortical dysplasia. Within the population with positive MAP findings (MAP+), seizure recurrence rates were 61.1% and 66.7% at 1 and 2 years after the first unprovoked seizure, respectively. Conversely, patients with negative MAP findings (MAP-) had lower seizure recurrence rates of 27.8% and 34.2% at 1 and 2 years after the first unprovoked seizure, respectively. Patients with MAP+ findings were significantly more likely to be diagnosed with epilepsy than those patients with MAP- findings (χ2 [1, n = 97] = 14.820, p < .001, odds ratio = 21.371, 95% CI = 2.710-168.531) during a mean follow-up time of 22.51 months (SD = 16.7 months, range = 1-61 months). SIGNIFICANCE: MRI postprocessing can be a valuable tool for detecting subtle epileptogenic lesions in patients with a first seizure and negative MRI results. Patients with first seizure and MAP+ findings had high seizure recurrence rates, meeting the criteria for beginning epilepsy.

Multimodal non-invasive evaluation in MRI-negative epilepsy patients.

Presurgical evaluation is still challenging for MRI-negative epilepsy patients. As non-invasive modalities are the easiest acceptable and economic methods in determining the epileptogenic zone, we analyzed the localization value of common non-invasive methods in MRI-negative epilepsy patients. In this study, we included epilepsy patients undergoing presurgical evaluation with presurgical negative MRI. MRI post-processing was performed using a Morphometric Analysis Program (MAP) on T1-weighted volumetric MRI. The relationship between MAP, magnetoencephalography (MEG), scalp electroencephalogram (EEG), and seizure outcomes was analyzed to figure out the localization value of different non-invasive methods. Eighty-six patients were included in this study. Complete resection of the MAP-positive regions or the MEG-positive regions was positively associated with seizure freedom (p = 0.028 and 0.007, respectively). When an area is co-localized by MAP and MEG, the resection of the area was significantly associated with seizure freedom (p = 0.006). However, neither the EEG lateralization nor the EEG localization showed statistical association with the surgical outcome (p = 0.683 and 0.505, respectively). In conclusion, scalp EEG had a limited role in presurgical localization and predicting seizure outcome, combining MAP and MEG results can significantly improve the localization of epileptogenic lesions and have a positive association with seizure-free outcome. PLAIN LANGUAGE SUMMARY: Due to the lack of obvious structure abnormalities on neuroimaging examinations, the identification of epilepsy lesions in MRI-negative epilepsy patients can be difficult. In this study, we intended to use non-invasive examinations to explore the potential epileptic lesions in MRI-negative epilepsy patients and to determine the results accuracy by comparing the neuroimaging results with the epilepsy surgery outcomes. A total of 86 epilepsy patients without obvious structure lesions on MRI were included, and we found that the combinations of different non-invasive examinations and neuroimaging post-processing methods are significantly associated with the seizure freedom results of epilepsy surgery.

[18F]SynVesT-1 and [18F]FDG quantitative PET imaging in the presurgical evaluation of MRI-negative children with focal cortical dysplasia type II.

PURPOSE: MRI-negative children with focal cortical dysplasia type II (FCD II) are one of the most challenging cases in surgical epilepsy management. We aimed to utilize quantitative positron emission tomography (QPET) analysis to complement [18F]SynVesT-1 and [18F]FDG PET imaging and facilitate the localization of epileptogenic foci in pediatric MRI-negative FCD II patients. METHODS: We prospectively enrolled 17 MRI-negative children with FCD II who underwent [18F]SynVesT-1 and [18F]FDG PET before surgical resection. The QPET scans were analyzed using statistical parametric mapping (SPM) with respect to healthy controls. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of [18F]SynVesT-1 PET, [18F]FDG PET, [18F]SynVesT-1 QPET, and [18F]FDG QPET in the localization of epileptogenic foci were assessed. Additionally, we developed a multivariate prediction model based on dual trace PET/QPET assessment. RESULTS: The AUC values of [18F]FDG PET and [18F]SynVesT-1 PET were 0.861 (sensitivity = 94.1%, specificity = 78.2%, PPV = 38.1%, NPV = 98.9%) and 0.908 (sensitivity = 82.4%, specificity = 99.2%, PPV = 93.3%, NPV = 97.5%), respectively. [18F]FDG QPET showed lower sensitivity (76.5%) and NPV (96.6%) but higher specificity (95.0%) and PPV (68.4%) than visual assessment, while [18F]SynVesT-1 QPET exhibited higher sensitivity (94.1%) and NPV (99.1%) but lower specificity (97.5%) and PPV (84.2%). The multivariate prediction model had the highest AUC value (AUC = 0.996, sensitivity = 100.0%, specificity = 96.6%, PPV = 81.0%, NPV = 100%). CONCLUSIONS: The multivariate prediction model based on [18F]SynVesT-1 and [18F]FDG PET/QPET assessments holds promise in noninvasively identifying epileptogenic regions in MRI-negative children with FCD II. Furthermore, the combination of visual assessment and QPET may improve the sensitivity and specificity of diagnostic tests in localizing epileptogenic foci and achieving a preferable surgical outcome in MRI-negative FCD II.

The clinical, imaging, pathological and genetic landscape of bottom-of-sulcus dysplasia.

Bottom-of-sulcus dysplasia (BOSD) is increasingly recognized as a cause of drug-resistant, surgically-remediable, focal epilepsy, often in seemingly MRI-negative patients. We describe the clinical manifestations, morphological features, localization patterns and genetics of BOSD, with the aims of improving management and understanding pathogenesis. We studied 85 patients with BOSD diagnosed between 2005-2022. Presenting seizure and EEG characteristics, clinical course, genetic findings and treatment response were obtained from medical records. MRI (3 T) and 18F-FDG-PET scans were reviewed systematically for BOSD morphology and metabolism. Histopathological analysis and tissue genetic testing were performed in 64 operated patients. BOSD locations were transposed to common imaging space to study anatomical location, functional network localization and relationship to normal MTOR gene expression. All patients presented with stereotyped focal seizures with rapidly escalating frequency, prompting hospitalization in 48%. Despite 42% patients having seizure remissions, usually with sodium channel blocking medications, most eventually became drug-resistant and underwent surgery (86% seizure-free). Prior developmental delay was uncommon but intellectual, language and executive dysfunction were present in 24%, 48% and 29% when assessed preoperatively, low intellect being associated with greater epilepsy duration. BOSDs were missed on initial MRI in 68%, being ultimately recognized following repeat MRI, 18F-FDG-PET or image postprocessing. MRI features were grey-white junction blurring (100%), cortical thickening (91%), transmantle band (62%), increased cortical T1 signal (46%) and increased subcortical FLAIR signal (26%). BOSD hypometabolism was present on 18F-FDG-PET in 99%. Additional areas of cortical malformation or grey matter heterotopia were present in eight patients. BOSDs predominated in frontal and pericentral cortex and related functional networks, mostly sparing temporal and occipital cortex, and limbic and visual networks. Genetic testing yielded pathogenic mTOR pathway variants in 63% patients, including somatic MTOR variants in 47% operated patients and germline DEPDC5 or NPRL3 variants in 73% patients with familial focal epilepsy. BOSDs tended to occur in regions where the healthy brain normally shows lower MTOR expression, suggesting these regions may be more vulnerable to upregulation of MTOR activity. Consistent with the existing literature, these results highlight (i) clinical features raising suspicion of BOSD; (ii) the role of somatic and germline mTOR pathway variants in patients with sporadic and familial focal epilepsy associated with BOSD; and (iii) the role of 18F-FDG-PET alongside high-field MRI in detecting subtle BOSD. The anatomical and functional distribution of BOSDs likely explain their seizure, EEG and cognitive manifestations and may relate to relative MTOR expression.

Yield of non-invasive imaging in MRI-negative focal epilepsy.

OBJECTIVE: The absence of MRI-lesion reduces considerably the probability of having an excellent outcome (International League Against Epilepsies [ILAE] class I-II) after epilepsy surgery. Surgical success in magnetic-resonance imaging (MRI)-negative cases relies therefore mainly on non-invasive techniques such as positron-emission tomography (PET), subtraction ictal/inter-ictal single-photon-emission-computed-tomography co-registered to MRI (SISCOM), electric source imaging (ESI) and morphometric MRI analysis (MAP). We were interested in identifying the optimal imaging technique or combination to achieve post-operative class I-II in patients with MRI-negative focal epilepsy. METHODS: We identified 168 epileptic patients without MRI lesion. Thirty-three (19.6%) were diagnosed with unifocal epilepsy, underwent surgical resection and follow-up ⩾ 2 years. Sensitivity, specificity, predictive values, and diagnostic odds ratio (OR) were calculated for each technique individually and in combination (after co-registration). RESULTS: 23/33 (70%) were free of disabling seizures (75.0% with temporal and 61.5% extratemporal lobe epilepsy). None of the individual modalities presented an OR > 1.5, except ESI if only patients with interictal epileptiform discharges (IEDs) were considered (OR 3.2). On a dual combination, SISCOM with ESI presented the highest outcome (OR = 6). MAP contributed to detecting indistinguishable focal cortical dysplasia in particular in extratemporal epilepsies with a sensitivity of 75%. Concordance of PET, ESI on interictal epileptic discharges, and SISCOM was associated with the highest chance for post-operative seizure control (OR = 11). CONCLUSION: If MRI is negative, the chances to benefit from epilepsy surgery are almost as high as in lesional epilepsy, provided that multiple established non-invasive imaging tools are rigorously applied and co-registered together.

Multimodal imaging-based diagnostic approach for MRI-negative posterior cortex epilepsy.

Background: Posterior cortex epilepsy (PCE) primarily comprises seizures originating from the occipital, parietal, and/or posterior edge of the temporal lobe. Electroclinical dissociation and subtle imaging representation render the diagnosis of PCE challenging. Improved methods for accurately identifying patients with PCE are necessary. Objectives: To develop a novel voxel-based image postprocessing method for better visual identification of the neuroimaging abnormalities associated with PCE. Design: Multicenter, retrospective study. Methods: Clinical and imaging features of 165 patients with PCE were retrospectively reviewed and collected from five epilepsy centers. A total of 37 patients (32.4% female, 20.2 ± 8.9 years old) with magnetic resonance imaging (MRI)-negative PCE were finally included for analysis. Image postprocessing features were calculated over a neighborhood for each voxel in the multimodality data. The postprocessed maps comprised structural deformation, hyperintense signal, and hypometabolism. Five raters from three different centers were blinded to the clinical diagnosis and determined the neuroimaging abnormalities in the postprocessed maps. Results: The average accuracy of correct identification was 55.7% (range from 43.2 to 62.2%) and correct lateralization was 74.1% (range from 64.9 to 81.1%). The Cronbach's alpha was 0.766 for the correct identification and 0.683 for the correct lateralization with similar results of the interclass correlation coefficient, thus indicating reliable agreement between the raters. Conclusion: The image postprocessing method developed in this study can potentially improve the visual detection of MRI-negative PCE. The technique could lead to an increase in the number of patients with PCE who could benefit from the surgery.

Skull-base temporal encephalocele: Hidden cause of temporal lobe epilepsy.

In the present study patients with previously diagnosed MRI-negative temporal lobe epilepsy (TLE) on long-term video electroencephalography (VEEG) monitoring were re-evaluated with high resolution 3T MRI brain to look out for a skull base temporal lobe encephalocoele (TE). A total of 234 VEEGs were analyzed. TLE had been diagnosed in 104 patients based on semiology, ictal, interictal EEG data, and brain positron emission tomography (PET) studies. Of these, 99 patients had temporal lobe abnormality (78 had mesial temporal sclerosis, 8 had tumor, 3 had focal cortical dysplasia, and 10 had mixed pathology). Out of the five 1.5T MRI-negative TLE patients, two patients were diagnosed with TE on subsequent 3T MRI brain scans and one patient underwent electrocorticography-guided tailored resection for complete removal of epileptogenic tissue; with Engels class I seizure freedom at one year follow-up. We propose that TE should be carefully searched for, as a cause of refractory TLE, using high-resolution MRI sequences.

Cushing's Disease Associated With Partially Empty Sella Turcica Syndrome: A Case Report.

The association between empty sella turcica (EST) syndrome and Cushing's disease has been rarely reported. It is plausible to hypothesize that EST syndrome in association with Cushing's disease can be attributed to intracranial hypertension. In this case report, we present a 47-year-old male patient who presented with weight loss, fatigue, easy bruising, acanthosis nigricans, and skin creases hyperpigmentation. Investigations revealed hypokalemia and confirmed the diagnosis of Cushing's disease. Magnetic resonance imaging (MRI) brain showed a partial EST syndrome and a new pituitary nodule as compared with previous brain imaging. Transsphenoidal surgery was pursued and was complicated by cerebrospinal fluid leakage. This case reflects the rare association of EST syndrome and Cushing's disease, suggesting the increased risk of postoperative complications in this setting and the diagnostic challenge that EST syndrome imposes. We review the literature for a possible mechanism of this association.

The utility of PET for detecting corticotropinomas in Cushing disease: a scoping review.

While magnetic resonance imaging (MRI) is the current standard imaging method for diagnosing and localizing corticotropinomas in Cushing disease, it can fail to detect adenomas in up to 40% of cases. Recently, positron emission tomography (PET) has shown promise as a diagnostic tool to detect pituitary adenomas in Cushing disease. We perform a scoping review to characterize the uses of PET in diagnosing Cushing disease, with a focus on describing the types of PET investigated and defining PET-positive disease. A scoping review was conducted following the PRISMA-ScR guidelines. Thirty-one studies fulfilled our inclusion criteria, consisting of 10 prospective studies, 8 retrospective studies, 11 case reports, and 2 illustrative cases with a total of 262 patients identified. The most commonly utilized PET modalities in prospective/retrospective studies were FDG PET (n = 5), MET PET (n = 5), 68 Ga-DOTATATE PET (n = 2), 13N-ammonia PET (n = 2), and 68 Ga-DOTA-CRH PET (n = 2). MRI positivity ranged from 13 to 100%, while PET positivity ranged from 36 to 100%. In MRI-negative disease, PET positivity ranged from 0 to 100%. Five studies reported the sensitivity and specificity of PET, which ranged from 36 to 100% and 50 to 100%, respectively. PET shows promise in detecting corticotropinomas in Cushing disease, including MRI-negative disease. MET PET has been highly investigated and has demonstrated excellent sensitivity and specificity. However, preliminary studies with FET PET and 68 Ga-DOTA-CRH PET show promise for achieving high sensitivity and specificity and warrant further investigation.

Management protocol and surgical techniques for MRI-Negative Cushing's disease: a series of 6 cases.

Up to 40% of Cushing's disease (CD) patients show no evidence of an adenoma on dynamic contrast-enhanced MRI. Inferior petrosal sinus sampling (IPSS) remains the gold standard for diagnosis in these patients. Remission rates in MRI-Negative CD are far less at 50%-71%, compared with patients in whom an adenoma is identified on MRI. Endoscopic endonasal transsphenoidal surgery is the surgical approach of choice in these cases. Various adjuncts can be used to localize an adenoma. In this video, the authors highlight their additional usage of pituitary perfusion MRI for identification of the adenoma. They present their stepwise management algorithm and surgical techniques for sellar and suprasellar exploration in 6 cases of MRI-Negative CD operated on by the senior author (A.S.). The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2318.

Endoscopic endonasal approach for MRI-Negative Cushing's microadenoma.

A 54-year-old male with a history of diabetes mellitus type 2 for 12 years and hypertension was seen in the clinic due to poorly controlled diabetes. Inferior petrosal sinus sampling (IPSS) confirmed Cushing's disease with primary adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma on the right. However, 3T and subsequent 7T MRI showed no visible tumor. An endoscopic transsphenoidal approach was selected to explore the pituitary gland and resect the presumed microadenoma. Tumor was identified in the lateral recess along the right medial cavernous sinus wall and gross-total resection (GTR) was performed. The normal pituitary gland was preserved, and the patient went into remission. The video can be found here: https://stream.cadmore.media/r10.3171/2023.4.FOCVID2324.

The clinical application of neuro-robot in the resection of epileptic foci: a novel method assisting epilepsy surgery.

During surgery for foci-related epilepsy, neurosurgeons face significant difficulties in identifying and resecting MRI-negative or deep-seated epileptic foci. Here, we present a neuro-robotic navigation system that is specifically designed for resection of MRI negative epileptic foci. We recruited 52 epileptic patients, and randomly assigned them to treatment group with either neuro-robotic navigation or conventional neuronavigation system. For each patient, in the neuro-robotic navigation group, we integrated multimodality imaging including MRI and PET-CT into the robotic workstation and marked the boundary of foci from the fused image. During surgery, this boundary was delineated by the robotic laser device with high accuracy, guiding resection for the surgeon. For deeply seated foci, we exploited the neuro-robotic navigation system to localize the deepest point with biopsy needle insertion and methylene dye application to locate the boundary of the foci. Our results show that, compared with the conventional neuronavigation, the neuro-robotic navigation system performs equally well in MRI positive epilepsy patients (ENGEL I ratio: 71.4% vs 100%, p = 0.255) systems and show better performance in patients with MRI-negative focal cortical dysplasia (ENGEL I ratio: 88.2% vs 50%, p = 0.0439). At present, there are no documented neurosurgery robots with similar function and application in the field of epilepsy. Our research highlights the added value of using neuro-robotic navigation systems in resection surgery for epilepsy, particularly in cases that involve MRI-negative or deep-seated epileptic foci.

Seizure features and outcomes in 50 children with GATOR1 variants: A retrospective study, more favorable for epilepsy surgery.

OBJECTIVES: To summarize the clinical features of epilepsy related to DEPDC5, NPRL2, and NPRL3 genes encoding the GATOR1 complex in children and to evaluate the factors affecting the prognosis of these epilepsies. METHODS: In this retrospective study, we reviewed the clinical and genetic characteristics of children with epilepsy related to GATOR1 variants who were admitted to the Peking University First Hospital between January 2016 and December 2021. Potential prognostic factors were assessed by comparing children with and without ongoing seizures. RESULTS: Fifty probands, including 31 boys and 19 girls were recruited. The median age at onset of epilepsy was 4 months, and 64% of patients had early-onset epilepsy (≤1 year). The most frequent epileptic seizure type was focal seizure (86%). Among the 50 patients, only six were with de novo variants. According to the novel classification framework for GATOR1 variants, 36 patients were with pathogenic variants and 14 with likely pathogenic variants. DEPDC5 variants were found in 37 patients, NPRL3 in 9, and NPRL2 in 4. The phenotype was similar among the probands, with variants in DEPDC5, NRPL2, or NPRL3. 76% (38/50) of epilepsy related to GATOR1 variants was neuroimaging positive, including brain MRI positive in 31 patients, and MRI combined F-18-fluorodeoxyglucose positron emission tomography positive in the other seven patients. Twenty-seven patients underwent epilepsy surgery. In total, after initial antiseizure medications alone, 92% (46/50) of patients were drug-resistant epilepsies, only 8% (4/50) of the probands became seizure-free but seizure-free (≥6 m) occurred in 92.6% (25/27) of patients with drug-resistant epilepsy after epilepsy surgery at the last follow-up. Patients undergoing epilepsy surgery had better epilepsy prognosis. SIGNIFICANCE: Epilepsy related to GATOR1 variants had high possibility to be drug-resistant epilepsy and to have positive neuroimaging finding. Epilepsy surgery is the only favorable factor for better seizure prognosis in this kind epilepsy.

Radiomics features from 3D-MPRAGE imaging can differentiate temporal-plus epilepsy from temporal lobe epilepsy.

OBJECTIVE: This study aimed to differentiate temporal-plus epilepsy (TPE) from temporal lobe epilepsy (TLE) using extraction of radiomics features from three-dimensional magnetization-prepared rapid acquisition gradient echo (3D-MPRAGE) imaging data. METHODS: Data from patients with TLE or TPE who underwent epilepsy surgery between January 2019 and January 2021 were retrospectively analyzed. Thirty-three regions of interest in the affected hemisphere of each patient were defined on 3D-MPRAGE images. A total of 3531 image features were extracted from each patient. Four feature selection methods and 10 machine learning algorithms were used to build 40 differentiation models. Model performance was evaluated using receiver operating characteristic analysis. RESULTS: Eighty-two patients were included for analysis, 47 with TLE and 35 with TPE. The model combining logistic regression and the relief selection method had the best performance (area under the receiver operating characteristic curve, .779; accuracy, .875; sensitivity, .800; specificity, .929; positive predictive value, .889; negative predictive value, .867). SIGNIFICANCE: Radiomics analysis can differentiate TPE from TLE. The logistic regression classifier trained with radiomics features extracted from 3D-MPRAGE images had the highest accuracy and best performance.