BACKGROUND: Cushing\'s disease (CD) is among the most common etiologies of hypercortisolism. Magnetic resonance imaging (MRI) is often utilized in the diagnosis of CD, however, up to 64% of adrenocorticotropic hormone (ACTH)-producing pituitary microadenomas are undetectable on MRI. We report 15 cases of MRI negative CD who underwent surgical resection utilizing a purely endoscopic endonasal approach.
METHODS: Endoscopic endonasal transsphenoidal surgery (EETS) was performed on 134 CD cases by a single surgeon. Fifteen cases met inclusion criteria: no conclusive MRI studies and no previous surgical treatment. Data collected included signs/symptoms, pre- and post-operative hormone levels, and complications resulting from surgical or medical management. Data regarding tumor diameter, location, and tumor residue/recurrence was obtained from both pre- and post-operative MRI. Immunohistochemistry was performed to assess for tumor hormone secretion.
RESULTS: Aside from a statistically significant difference (P = 0.001) in histopathological results between patients with negative and positive MRI, there were no statistically significant difference between these two groups in any other demographic or clinical data point. Inferior petrosal sinus sampling (IPSS) with desmopressin (DDAVP®) administration was performed on the 15 patients with inconclusive MRIs to identify the origin of ACTH hypersecretion via a central/peripheral (C/P) ratio. IPSS in seven, five and three patients showed right, left, and central side lateralization, respectively. With a mean follow-up of 5.5 years, among MRI-negative patients, 14 (93%) and 12 patients (80%) achieved early and long-term remission, respectively. In the MRI-positive cohort, over a mean follow-up of 4.8 years, 113 patients (94.9%) and 102 patients (85.7%) achieved initial and long-term remission, respectively.
CONCLUSIONS: Surgical management of MRI-negative/inconclusive Cushing\'s disease is challenging scenario requiring a multidisciplinary approach. An experienced neurosurgeon, in collaboration with a dedicated endocrinologist, should identify the most likely location of the adenoma utilizing IPSS findings, followed by careful surgical exploration of the pituitary to identify the adenoma.

BACKGROUND: This study aimed to investigate the number of cores needed in a systematic biopsy (SB) in men with clinical suspicion of prostate cancer (PCa) but negative prebiopsy multiparametric magnetic resonance imaging and to test prostate-specific antigen (PSA) density as an indicator for reduced SB.
METHODS: Two hundred and seventy-four patients were analyzed, extracted from an institutional database. Detection rates of any PCa and clinically significant (CS) PCa for different reduced biopsy protocols were compared by using Fisher\'s exact test.
RESULTS: In total, 12-core SB revealed PCa in 103 (37.6%) men. Detection rates of reduced biopsy protocols were 74 (27%, 6-core) and 82 (29.9%, 8-core). Regarding CSPCa, 12-core SB revealed a detection rate of 26 (9.5%). Reduced biopsy protocols detected less CSPCa: 15 (5.5%) and 18 (6.6%), respectively. All differences were statistically significant, p < 0.05. PSA density ≥0.15 did not help to filter out men in whom a reduced biopsy may be sufficient.
CONCLUSIONS: Twelve-core SB still has the highest detection rate of any PCa and CSPCa compared to reduced biopsy protocols. If the investigator and patient agree - based on individual risk calculation - to perform a biopsy, this SB should contain at least 12 cores regardless of PSA density.

UNASSIGNED: Prostatic multi-parametric magnetic resonance imaging (mpMRI) has markedly improved the assessment of men with suspected prostate cancer (PCa). Nevertheless, as mpMRI exhibits a high negative predictive value, a negative MRI may represent a diagnostic dilemma. The aim of this study was to evaluate the incidence of positive transperineal saturation biopsy in men who have negative mpMRI and to analyse the factors associated with positive biopsy in this scenario.
UNASSIGNED: A retrospective study of men with normal mpMRI and suspicion of PCa who underwent saturation biopsy (≥20 cores) was carried out. A total of 580 patients underwent transperineal MRI/transrectal ultrasound fusion targeted biopsies or saturation prostate biopsies from January 2017 to September 2020. Of them, 73 had a pre-biopsy negative mpMRI (with Prostate Imaging - Reporting and Data System, PI-RADS, ≤2) and were included in this study. Demographics, clinical characteristics, data regarding biopsy results and potential predictive factors of positive saturation biopsy were collected. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for MRI-invisible PCa.
UNASSIGNED: The detection rate of PCa with saturation biopsy in patients with negative MRI was 34/73 (46.58%). Out of 34 MRI-invisible prostate cancers detected, 12 (35.29%) were clinically significant PCa (csPCa) forms. Regarding factors of positive biopsy, in univariate analysis, the use of 5-alpha reductase inhibitors and free:total prostate-specific antigen (PSA) ratio were associated with the result of the saturation biopsy. In multivariate analysis, only an unfavourable free:total PSA ratio remained a risk factor (OR 11.03, CI95% 1.93-63.15, p=0.01). Furthermore, multivariate logistic analysis demonstrated that prostate volume >50mL significantly predicts the absence of csPCa on saturation biopsy (OR 0.11, 95% CI 0.01-0.94, p=0.04).
UNASSIGNED: A free:total PSA ratio <20% is a risk factor for MRI-invisible PCa. Saturation biopsy could be considered in patients with suspected PCa, despite having a negative MRI.

BACKGROUND: The interpretation of negative magnetic resonance imaging (MRI) screening results for clinically significant prostate cancer (csPCa) (International Society of Urological Pathology grade ≥group 2) is debatable and poses a clinical dilemma for urologists. No nomograms have been developed to predict csPCa in such populations. In this study, we aimed to develop and validate a model for predicting the probability of csPCa in men with negative MRI (PI-RADS score 1-2) results after transrectal ultrasound-guided systematic prostate biopsy.
METHODS: The development cohort consisted of 728 patients with negative MRI results who underwent subsequent prostate biopsy at our center between January 1, 2014 and December 31, 2017. The patients\' clinicopathologic data were recorded. The Lasso regression was used for data dimension reduction and feature selection, then multivariable binary logistic regression was used to build a predictive model with regression coefficients. The model was validated in an independent cohort of 334 consecutive patients from January 1, 2018 and June 30, 2020. The performance of the predictive model was assessed with respect to discrimination, calibration, and decision curve analysis.
RESULTS: The predictors incorporated in this model included age, history of previous negative prostate biopsy, prostate specific antigen density (PSAD), and lower urinary tract symptoms, with PSAD being the strongest predictor. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval, 0.816-0.933) and good calibration (unreliability test, p = .540). Decision curve analysis demonstrated that the model was clinically useful.
CONCLUSIONS: This study presents a good nomogram that can aid pre-biopsy risk stratification for the detection of csPCa, and that may help inform biopsy decisions in patients with negative MRI results.

To assess the utility of interictal magnetic and electric source imaging (MSI and ESI) using dipole clustering in magnetic resonance imaging (MRI)-negative patients with drug resistant epilepsy (DRE).
We localized spikes in low-density (LD-EEG) and high-density (HD-EEG) electroencephalography as well as magnetoencephalography (MEG) recordings using dipoles from 11 pediatric patients. We computed each dipole\'s level of clustering and used it to discriminate between clustered and scattered dipoles. For each dipole, we computed the distance from seizure onset zone (SOZ) and irritative zone (IZ) defined by intracranial EEG. Finally, we assessed whether dipoles proximity to resection was predictive of outcome.
LD-EEG had lower clusterness compared to HD-EEG and MEG (p < 0.05). For all modalities, clustered dipoles showed higher proximity to SOZ and IZ than scattered (p < 0.001). Resection percentage was higher in optimal vs. suboptimal outcome patients (p < 0.001); their proximity to resection was correlated to outcome (p < 0.001). No difference in resection percentage was seen for scattered dipoles between groups.
MSI and ESI dipole clustering helps to localize the SOZ and IZ and facilitate the prognostic assessment of MRI-negative patients with DRE.
Assessing the MSI and ESI clustering allows recognizing epileptogenic areas whose removal is associated with optimal outcome.

OBJECTIVE: Prostate biopsy should be discussed with the patient in cases of negative magnetic resonance imaging and low clinical suspicion of prostate cancer.Our primary objective was to describe the risk of clinically significant prostate cancer in a negative magnetic resonance imaging biopsy naïve population at baseline and during long-term followup. The secondary objective was to evaluate clinical factors and prostate specific antigen as predictors of clinically significant prostate cancer at baseline.
METHODS: All 503 consecutive patients who were biopsy naïve referred from 2007 to 2017 for biopsy with negative magnetic resonance imaging (PI-RADS™ 1-2) who had systematic 12-core biopsies at baseline were included. Clinical factors were digital rectal examination, prostate cancer family history and prostate specific antigen. In case of suspicious digital rectal examination or prostate specific antigen kinetics during followup, magnetic resonance imaging and biopsy were performed. Clinically significant prostate cancer was defined as either Gleason Grade 1 with cancer core length greater than 5 mm or 3 or more positive systematic 12-core biopsies in addition to Gleason Grade 2 or greater (clinically significant prostate cancer-1) or any Gleason Grade 2 or greater (clinically significant prostate cancer-2). Nonclinically significant prostate cancer was defined as either Gleason Grade 1 with cancer core length 5 mm or less and fewer than 3 positive systematic 12-core biopsies (nonclinically significant prostate cancer-1) or any Gleason Grade 1 (nonclinically significant prostate cancer-2). Definition of high risk clinically significant prostate cancer was Gleason Grade 3 or greater. Univariate and multivariate models were fitted to identify predictors of clinically significant prostate cancer risk.
RESULTS: At baseline, biopsy showed clinically significant prostate cancer-1 in 9% (45), clinically significant prostate cancer-2 in 6% (29) and nonclinically significant prostate cancer in 22% (111). At median followup of 4 years (IQR 1.6-7.1), 31% (95% CI 27-36) of 415 untreated patients had a second magnetic resonance imaging and 24% (95% CI 20-28) a second biopsy that showed clinically significant prostate cancer-1 in 5% (21/415, 95% CI 3-7), clinically significant prostate cancer-2 in 2% (7/415, 95% CI 1-3) and nonclinically significant prostate cancer in 8%. Overall incidence was 13% (66/503, 95% CI 7-21) for clinically significant prostate cancer-1, 7% (36/503, 95% CI 5-9%) for clinically significant prostate cancer-2 and 2% (12/503, 95% CI 1.1-3.7) for high risk prostate cancer. Predictors of clinically significant prostate cancer risk were prostate specific antigen density 0.15 ng/ml/ml or greater (OR 2.43, 1.19-4.21), clinical stage T2a or greater (OR 3.32, 1.69-6.53) and prostate cancer family history (OR 2.38, 1.10-6.16). Performing biopsy in patients with negative magnetic resonance imaging and prostate specific antigen density 0.15 ng/ml/ml or greater or abnormal digital rectal examination or prostate cancer family history would have decreased from 9% to 2.4% the risk of missing clinically significant prostate cancer-1 at baseline while avoiding biopsy in 56% of cases.
CONCLUSIONS: The risk of clinically significant prostate cancer in a negative magnetic resonance imaging biopsy naïve population was 6% to 9% at baseline and 7% to 13% at long-term followup depending on clinically significant prostate cancer definitions.

BACKGROUND: A significant proportion of patients presenting with suspected cauda equina syndrome (CES) do not have associated radiological evidence to support the diagnosis, often termed \'scan-negative\'. Due to the limited number of studies regarding the matter, there is no clear understanding for this presentation. As a result, no treatment protocol exists for the scan-negative group. The purpose of this review is to assess the potential contributing factors leading to the presentation of suspected CES with normal imaging.
METHODS: A systematic review was conducted on PubMed and Cochrane databases. Bibliographies of key articles and Google Scholar were searched for additional results. The search strategy provided 204 results. Of those, 8 had no identifiable causation for suspected CES and were included for systematic review.
RESULTS: 6 of 8 studies investigated for a difference in clinical presentation between cohorts that may indicate a normal scan. Studies were either inconclusive and contradictory. Two studies suggest a functional somatic disorder as reasoning for negative MRI, with positive provisional findings.
CONCLUSIONS: A psychogenic hypothesis is plausible and warrants further investigation. The need for additional studies is essential to scheming a potential treatment protocol for the scan-negative population, which currently does not exist.

OBJECTIVE: Magnetoencephalography (MEG) is considered to be a useful clinical tool to provide additional information for localising the epileptogenic zone or planning intracranial electrode implantation. This study aimed to evaluate the value of MEG in the presurgical localisation of the operculo-insular epileptogenic zone in patients with negative magnetic resonance imaging (MRI).
METHODS: Thirteen patients with operculo-insular epilepsy and negative MRI who were identified by presurgical evaluation and underwent resective surgery from January 2011 to June 2015 were included and analysed in the study.
RESULTS: In presurgical evaluation, the ictal symptoms looked reliable enough to characterise operculo-insular seizures in four patients. MEG spike sources were shown in the operculo-insular region in 11 of 13 (84.6%) patients, including cluster spike sources in 7 patients and scatter spike sources in 4 patients. After MEG examination, the original plan of intracranial electrode implantation was changed in five patients. In these patients, electrodes exploring the operculo-insular cortex were not part of the original plan. The pathological examination showed focal cortical dysplasia (FCD) in 12 patients and FCD with heterotopia in 1 patient. Nine (69.2%)patients were seizure-free in 2-6 years\' follow-up.
CONCLUSIONS: MEG played an additional and valuable role in the localisation of operculo-insular epilepsy for patients with a negative MRI finding.

This review considers accumulating evidence for a new role of MEG/MSI in increasing the diagnostic yield of supposedly negative MRIs, and suggests changes in the use of MEG/MSI in presurgical epilepsy evaluations. Specific alterations in practice protocols for both the MEG practitioner (i.e. physician magnetoencephalographer) and MEG user (i.e. referring physician) are proposed that should further enhance the overall value of MEG/MSI. Although advances in MEG analysis methods will likely become increasingly assisted by computers, interpretive competency and prudent clinical judgment remain irreplaceable.

Meningeal involvement of multiple myeloma is rare. A patient with multiple myeloma presented with bilateral abducens nerve palsies. In the MRI neither lytic skull lesions nor meningeal enhancement could be found. The diagnosis was based on CSF studies and cytology. A neurologic remission was achieved with intrathecal chemotherapy.