MRI Abnormalities Research Articles

Cognitive and MRI Profiles in Primary and Secondary Progressive Multiple Sclerosis (P13-3.002)

<h3>Objective:</h3> We examined the neuropsychological profile of primary progressive (PP) and secondary progressive (SP) multiple sclerosis (MS) patients and investigated the relationship between cognitive functioning with structural and functional MRI abnormalities. <h3>Background:</h3> Studies comparing frequency and patterns of cognitive dysfunction between PPMS and SPMS have yielded conflicting results. <h3>Design/Methods:</h3> One-hundred eighty-three MS patients (60 PPMS and 123 SPMS) and 75 age- and sex-matched healthy controls underwent 3.0T MRI. MS patients were administered the Brief Repeatable Battery of Neuropsychological tests (BRB-N) and were classified as cognitively impaired if they scored below the 5^th percentile of the normative sample on at least two tests. Four cognitive domain z-scores were determined from normative data, and then averaged to obtain a measure of global cognition (z-BRB-N). Using hierarchical linear regression analysis, the contribution of lesion volumes, normalized brain volumes, white matter fractional anisotropy (FA) and mean diffusivity (MD) abnormalities, and resting state (RS) functional connectivity (FC) alterations to global cognition in PPMS and SPMS was investigated. <h3>Results:</h3> Patients with PPMS and SPMS had similar z-scores in all investigated cognitive domains. Compared to PPMS, SPMS showed decreased FA and increased MD in the fornix, and lower RS FC within the basal ganglia network. The frequency of cognitive impairment was 31.7% in PPMS and 41.3% in SPMS (p=0.19). In PPMS, poorer cognitive performance (e.g., lower z-BRB-N) was associated with decreased FA of the medial lemniscus (ΔR²=0.11; p=0.011) and lower normalized gray matter volume (ΔR²=0.29; p&lt;0.001). In SPMS, poorer cognitive performance was associated with decreased FA of the fornix (ΔR²=0.35; p&lt;0.001) and lower normalized white matter volume (ΔR²=0.05; p=0.034). <h3>Conclusions:</h3> PPMS and SPMS had similar neuropsychological profile. Cognitive dysfunction in PPMS and SPMS was related to distinct patterns of structural MRI abnormalities and involvement of different white matter tracts, while RS FC alterations did not contribute to explain their global cognitive functioning. <b>Disclosure:</b> Damiano Mistri has nothing to disclose. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOMEDIA. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Elisabetta Pagani has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Dramatic Improvement of MRI Abnormalities of HIV Dementia after Suppressive Antiretroviral Therapy (S25.002)

<h3>Objective:</h3> Not applicable. <h3>Background:</h3> A 59-year-old man diagnosed with HIV 26 years prior and a long history of antiretroviral therapy (ART) non-adherence presented with subacute cognitive decline. A neurologic workup including cerebrospinal fluid testing showed no evidence of opportunistic infections. He was admitted to an assisted care facility where he restarted ART. However, he remained viremic and was referred to the National Institutes of Health (NIH). On admission to the NIH, he had an HIV plasma viral load of 28,056 copies/mL and CD4 T-cell count of 5 cells/μL. He was started on a new ART regimen with increased central nervous system penetration (etravirine, dolutegravir, darunavir/cobicistat, tenofovir/emtricitabine). MRI revealed extensive leukoencephalopathy and volume loss, consistent with HIV encephalopathy. Comprehensive neuropsychological testing revealed significant deficits in all cognitive domains, including learning, memory, attention, executive function, and psychomotor speed. The patient was followed for two years, during which time he achieved and sustained viral suppression (&lt;40 copies/mL) and reached a CD4 T-cell count of 197 with ART. A repeat MRI showed profound improvement in the white matter signal abnormality. Repeat neuropsychological testing demonstrated notable improvements in several tests of attention, information processing, and psychomotor speed, but continued difficulty in most other cognitive domains. <h3>Design/Methods:</h3> Not applicable. <h3>Results:</h3> Not applicable. <h3>Conclusions:</h3> While current ART regimens are highly effective in reducing the incidence of HIV-associated neurologic complications, their role in reversing the MRI abnormalities seen in HIV encephalopathy remains unclear. In this case, we tracked HIV encephalopathy in the current era of effective ART with serial MRI evaluations. Our results provide a rare example of dramatic reduction of periventricular white matter hyperintensities and improved performance in a subset of cognitive domains. Providers encountering white matter abnormalities in patients with treated HIV should consider this legacy effect in evaluating whether disease is progressive, or as in this case, improved. <b>Disclosure:</b> Ms. Dietrich has nothing to disclose. Miss Laidlaw has nothing to disclose. Dr. Hammoud has nothing to disclose. Dr. Pau has nothing to disclose. Dr. Smith has nothing to disclose.

Immunotherapy Responsiveness and Risk of Relapse in Down Syndrome Regression Disorder (S34.003)

<h3>Objective:</h3> This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation in persons with Down Syndrome Regression Disorder (DSRD). <h3>Background:</h3> Down syndrome regression disorder (DSRD) is a clinical symptom cluster consisting of neuropsychiatric regression without an identifiable cause. Although presumably polyfactorial, a minority of individuals with this condition have been found to have inflammatory biomarkers and are immunotherapy responsive. This study evaluated the clinical effectiveness of IVIg and evaluated clinical characteristics associated with relapse after therapy discontinuation. <h3>Design/Methods:</h3> A prospective, multi-center, non-randomized, observational study was performed. Patients met criteria for DSRD and were treated with IVIg. All patients underwent a standardized wean off therapy after 9–12 months of treatment. Baseline, on therapy, and relapse scores of the Neuropsychiatric Inventory Total Score (NPITS), Clinical Global Impression-Severity (CGI-S), and the Bush-Francis Catatonia Rating Scale (BFCRS) were used to track clinical symptoms. <h3>Results:</h3> Eighty-two individuals were enrolled in this study. Patients had lower BFCRS (MD: −6.68; 95% CI: −8.23, −5.14), CGI-S (MD: −1.27; 95% CI: −1.73, −0.81), and NPITS scores (MD: −6.50; 95% CI: −7.53, −5.47) while they were on therapy compared to baseline. Approximately 46% of the patients (n = 38) experienced neurologic relapse with wean of IVIg. Patients with neurologic relapse were more likely to have any abnormal neurodiagnostic study (χ2 = 11.82, p = 0.001), abnormal MRI (χ2 = 7.78, p = 0.005), and abnormal LP (χ2 = 5.45, p = 0.02), and a personal history of autoimmunity (OR: 6.11, p&lt;0.001) compared to patients without relapse. <h3>Conclusions:</h3> IVIg was highly effective in the treatment of DSRD. Individuals with a history of personal autoimmunity or neurodiagnostic abnormalities were more likely to relapse following weaning of immunotherapy, indicating the potential for, a chronic autoimmune etiology in some cases of DSRD. <b>Disclosure:</b> Dr. Santoro has received personal compensation for serving as an employee of UCB. Dr. Santoro has received personal compensation for serving as an employee of Cycle Pharma. Dr. Spinazzi has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Zalkin Law Firm. The institution of Dr. Spinazzi has received research support from Konica Minolta. The institution of an immediate family member of Dr. Filipink has received research support from NIH . Dr. Filipink has received personal compensation in the range of $0-$499 for serving as a Author with Medlink. Dr. Hayati Rezvan has nothing to disclose. The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. The institution of Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Kammeyer has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Ogborn-Mihm Trial Lawyers. The institution of Dr. Kammeyer has received research support from Rocky Mountain Multiple Sclerosis Center. Dr. Patel has nothing to disclose. The institution of Dr. Sannar has received research support from Colorado Department of Public Health and Environment. The institution of Dr. Sannar has received research support from National Institute of Health. Dr. Dwyer has nothing to disclose. Dr. Banerjee has nothing to disclose. Dr. Khoshnood has nothing to disclose. Dr. Jafarpour has nothing to disclose. Ms. Boyd has nothing to disclose. Dr. Partridge has nothing to disclose. The institution of Dr. Gombolay has received research support from CDC. The institution of Dr. Gombolay has received research support from NIH. Dr. Christy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for SAGE Publishing. Dr. Christy has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for The Becker Law Firm . The institution of Dr. Christy has received research support from Biohaven. Dr. ORTEGA BERNARDO has nothing to disclose. Dr. Manning has nothing to disclose. Dr. Van Mater has nothing to disclose. Dr. Worley has nothing to disclose. Dr. Franklin has nothing to disclose. The institution of Dr. Stanley has received research support from NIH. The institution of Dr. Stanley has received research support from NIH. Dr. Brown has nothing to disclose. The institution of George Capone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ACImmune. The institution of George Capone has received research support from LuMind. Dr. Quinn has nothing to disclose. Dr. Rafii has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AC Immune. Dr. Rafii has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Keystone Bio. Dr. Rafii has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alzheon.

Nystagmus Response to Thiamine Replacement, a Predictor of Wernicke-Korsakoff (WE) Syndrome Outcome. A 21-patient Cohort Study (S12.002)

<h3>Objective:</h3> To identify an easily recognizable clinical marker of thiamine deficiency to procure timely diagnosis <h3>Background:</h3> Wernicke’s Encephalopathy (WE) treatment outcome depends on genetic factors, duration of insufficient thiamine, metabolic demand and comorbidities. Nystagmus is by far the most frequent ocular motor finding abnormality in thiamine deficiency. Its response to treatment predicts outcome. <h3>Design/Methods:</h3> This is a retrospective series of 21-patient cohort, 16 acute patients, studied as on-going acute vestibular syndrome/ataxia cohort (two telemedicine), and 5 outpatients. All underwent neurological and neurophthalmologic examination and nystagmus recordings, they had at least one abnormal ancillary test; low serum pre-treatment thiamine, or abnormal head MRI. <h3>Results:</h3> Nine patients had horizontal (h) nystagmus (two types: vestibular and gaze holding nystagmus); thiamine replacement led to rapid nystagmus resolution, and prevented encephalopathy in all (including one, who had also upbeat nystagmus/truncal ataxia (UBN/TA), one patient has chronic UBN/TA for one year with improving WE at a slower pace. Six patients had conversion from UBN to permanent downbeat nystagmus/truncal ataxia (DBN/TA), and slower WE recovery; one patient had improved UBN/TA. Three outpatients with permanent DBN/TA had a previous history and labs compatible with thiamine deficiency. One patient did not have nystagmus. None of the study-cohort patients developed Korsakoff’s syndrome (KS). <h3>Conclusions:</h3> In patients at WE risk, h-nystagmus was the earliest sign of thiamine deficiency in this cohort, had the fastest response to thiamine, which also prevented WE. Vertical nystagmus had longer WE recovery, and six patients had enduring DBN/TA. Interestingly, none of the 21 patients developed KS. This series highlight the key role of nystagmus analysis in thiamine deficiency. Adding nystagmus to Caine’s diagnostic criteria may enhance the early features of thiamine deficiency. <b>Disclosure:</b> Dr. Kattah has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Bonezzi, Switzer , Poilitto and Hupp Legal Firm.

Metabolic Stroke as a Clinical Manifestation of Zhu-Tokita-Takenouchi-Kim (ZTTK) Syndrome: A Case Series (P14-9.010)

<h3>Objective:</h3> To report two individuals with Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome who presented with a metabolic stroke, which has rarely been described as a clinical manifestation of this syndrome. <h3>Background:</h3> ZTTK syndrome is a rare condition caused by a loss-of-function mutation in the <i>SON</i> gene, which is located in chromosome region 21q22, and there are approximately 60 known cases.¹ The <i>SON</i> gene is involved in cellular and mitochondrial processes, but much is still unknown.^2,5,6 The commonly associated clinical manifestations of this condition are global developmental delay, dysmorphic facial features, musculoskeletal abnormalities, abnormal brain MRI, hypotonia, eye anomalies, seizures, and short stature.¹ Here we report two individuals who presented to our institution with a metabolic stroke, which has rarely been described previously other than a single reported case.³ As ZTTK syndrome remains a rare disease, reports which expand the clinical phenotype will help inform clinicians of previous findings, diagnoses, and management strategies. <h3>Design/Methods:</h3> Case series <h3>Results:</h3> Two female children, 11 and 12-year-old, presented very similarly to our institution with sudden left hemiparesis and right gaze preference. Both girls carried a diagnosis of ZTTK syndrome based on their clinical characteristics and genetic testing. Both girls were found to have a metabolic stroke on their MRI brain after extensive workup. The 12-year-old girl was treated with L-arginine, levocarnitine, and ubiquinone, which has been used to treat metabolic strokes in mitochondrial disorders. The 11-year-old girl did not receive any particular treatment for stroke. Both individuals returned to their previous functional baseline within two weeks. <h3>Conclusions:</h3> Metabolic stroke is a rare clinical manifestation of ZTTK syndrome. It is important to recognize metabolic stroke as an etiology of sudden hemiplegia in ZTTK syndrome as it carries clinical and therapeutic implications. Further studies are needed to determine the cause of metabolic stroke in this syndrome. <b>Disclosure:</b> Dr. Morales has nothing to disclose. Ms. El-said has nothing to disclose. Dr. Rossi has nothing to disclose. Dr. Longani has nothing to disclose.

Non-epileptic paroxysmal events at pediatric video-electroencephalography monitoring unit over a 15-year period

ObjectiveNon-epileptic paroxysmal events (NEPEs) are common in pediatric patients and may be misdiagnosed as epileptic seizures. We aimed to study the distribution of NEPEs across age groups and with different comorbidities, and to correlate the patients' presenting symptoms with their final diagnosis after video-EEG. MethodsWe retrospectively analyzed video-EEG recordings of children aged one month to 18 years who were admitted between March 2005 and March 2020. Patients who experienced any NEPE while under video-EEG monitorization were evaluated in this study. Subjects with concomitant epilepsy were also included. The patients were first divided into 14 groups according to the basic characteristics of symptoms they reported at admission. The events captured on video-EEG were then classified into six NEPE categories based on the nature of the events. These groups were compared according to video-EEG results. ResultsWe retrospectively evaluated 1338 records of 1173 patients. The final diagnosis was non-epileptic paroxysmal event in 226 (19.3%) of 1173 patients. The mean age of the patients was 105.4 ± 64.4 months at the time of the monitoring. The presenting symptoms were motor in 149/226 (65.9%) patients, with jerking being the most common (n = 40, 17.7%). Based on video-EEG, the most common NEPE was psychogenic non-epileptic seizures (PNES) (n = 66, 29.2%), and the most common PNES subtype was major motor movements (n = 19/66, 28.8%). Movement disorders (n = 46, 20.4%) were the second most common NEPE and the most common NEPE (n = 21/60, 35%) in children with developmental delay (n = 60). Other common NEPEs were physiological motor movements during sleep (n = 33, 14.6%), normal behavioral events (n = 31, 13.7%), and sleep disorders (n = 15, 6.6%). Almost half of the patients had a prior diagnosis of epilepsy (n = 105, 46.5%). Following the diagnosis of NEPE, antiseizure medication (ASM) was discontinued in 56 (24.8%) patients. ConclusionNon-epileptiform paroxysmal events can be difficult to distinguish from epileptic seizures in children, especially in patients with developmental delay, epilepsy, abnormal interictal EEG, or abnormal MRI findings. Correct diagnosis of NEPEs by video-EEG prevents unnecessary ASM exposure in children and guides appropriate management of NEPEs.

Teaching NeuroImages: MRI abnormalities in frontal lobe seizures due to nonketotic hyperglycemia

A 56-year-old woman presented with electroclinical focal seizures in the setting of hyperglycemia (808 mg/dL) and elevated HbA1c of 14.7%. She had varying seizure semiology, consisting of early forced head turn to the left, speech arrest, left facial twitching, and impaired awareness. Her seizures arose from the right frontotemporal area on EEG (figure 1). MRI showed hypointensities in the right prefrontal lobe that resolved after 6 months (figure 2).

Risk factors for drug-resistant epilepsy in adult patients

IntroductionDrug-resistant epilepsy occurs in about 30% of epilepsy patients. It has been suggested that etiology or seizure type would increase the risk of pharmacoresistance. This study aims to compare the characteristics of patients with drug-sensitive epilepsy with patients with drug-resistant epilepsy to identify risk factors. Patient and methodsA multicentric cohort study was conducted between 2019 and 2022. We included patients >18 years-old with epilepsy but excluded psychogenic non-epileptic seizures and less than 2 years of follow-up. ResultsWe included 128 patients, of whom 46 had drug-resistance epilepsy, and 82 responding to medication. Both groups showed similar characteristics. Febrile seizures (OR: 7.25), focal epilepsy (OR: 2.4), focal seizures with loss of consciousness (OR: 2.36), structural etiology (OR: 2.2) and abnormal MRI (OR: 4.6) were significant risk factors for drug-resistance epilepsy. ConclusionFollowing other studies, we observed that factors such as epilepsy type, seizure type, structural etiology, abnormal MRI, and febrile seizure increased the risk for drug-resistance epilepsy, in our population.

How can we differentiate supratentorial tumor recurrence from postradiation imaging changes in children treated for primary malignant brain tumors?

Distinguishing tumor recurrence from therapy-induced imaging changes (TIIC) on brain MRI in children treated for primary malignant brain tumors may be challenging. The authors aimed to assess the diagnostic ability of multimodal MRI in differentiating TIIC from tumor recurrence. The authors retrospectively included children with abnormal supratentorial brain MRI findings after treatment for primary malignant brain tumors (regardless of their localization) with complete resection and radiotherapy. A total of 18 patients with TIIC and 25 patients with tumor recurrence were compared, according to structural, apparent diffusion coefficient (ADC), and arterial spin labeling (ASL) imaging data accrued over time. TIIC were defined by a new MRI scan that was stable for at least 1 year or had regressed, or by histopathology findings in specimens obtained when the anomaly was surgically treated. The time interval between completion of radiotherapy and the appearance of abnormal brain MRI findings was significantly shorter in the TIIC group compared with the tumor recurrence group (median 6 vs 35 months; p < 0.001). TIIC appeared as foci of increased T2-weighted signal intensity, without nodule, associated with variable contrast enhancement. Tumor recurrence appeared as a well-defined nodule with intermediate signal intensity on T2-weighted images with nodular contrast enhancement. Relative ADC values were significantly higher in the TIIC group (median 1.43 vs 0.88; p < 0.001). Relative ASL-cerebral blood flow (CBF) values were significantly lower in the TIIC group (median 0.27 vs 0.43; p = 0.04). On follow-up MRI, TIIC could progress, regress, or remain stable. In most instances (72%), they decreased in size or remained stable at 4 years of follow-up. MRI features of TIIC include foci of increased signal intensity without a demonstrable nodule on T2-weighted images, high ADC values, and lower ASL-CBF values, whereas tumor recurrence appears as a well-defined nodule with low ADC values and higher ASL-CBF values.

MP40-12 INTENSIFIED PROSTATE CANCER SCREENING IN GERMLINE CARRIERS OF RARE PATHOGENIC VARIANTS: INTERIM RESULTS FROM THE INITIAL SCREENING ROUND OF THE PROGRESS STUDY

You have accessJournal of UrologyCME1 Apr 2023MP40-12 INTENSIFIED PROSTATE CANCER SCREENING IN GERMLINE CARRIERS OF RARE PATHOGENIC VARIANTS: INTERIM RESULTS FROM THE INITIAL SCREENING ROUND OF THE PROGRESS STUDY Keyan Salari, Alexandra Hunter, Andrew Amini, Aya Almashad, Shelley McCormick, and Linda Rodgers Keyan SalariKeyan Salari More articles by this author , Alexandra HunterAlexandra Hunter More articles by this author , Andrew AminiAndrew Amini More articles by this author , Aya AlmashadAya Almashad More articles by this author , Shelley McCormickShelley McCormick More articles by this author , and Linda RodgersLinda Rodgers More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003278.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Men with germline pathogenic variants in prostate cancer risk genes (e.g., BRCA2) may be at increased risk of developing aggressive prostate cancer and thus warrant special considerations regarding prostate cancer screening. The Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS) is evaluating an intensified screening program for men at high genetic risk for prostate cancer that incorporates prostate MRI-based screening for early detection of prostate cancer. METHODS: Men between 35-75 years old with a pathogenic/likely pathogenic germline variant in one of 19 prostate cancer risk genes and no prior diagnosis of prostate cancer were prospectively enrolled. Screening paradigm included annual DRE and PSA testing and a multiparametric MRI of the prostate every three years. PSA was considered elevated using an age-adjusted threshold of >1.5 ng/mL for 35-49 years of age, >2.0 ng/mL for 50-54 years of age, and >3.0 ng/ml for 55-70 years of age. Patients with an abnormal DRE, elevated age-adjusted PSA, or a positive MRI (PI-RADS ≥3) were recommended to undergo prostate biopsy. RESULTS: A total of 81 patients have been enrolled to date, 78 of whom have completed the first round of screening. Median age is 55 years (45-64), and median PSA is 0.84 ng/mL (0.57-1.76). Most patients harbored pathogenic variants in either BRCA2 (n=31 [39%]) or BRCA1 (n=29 [37%]). After the first round of screening, 2 (3%) patients had an abnormal DRE, 10 (13%) had an elevated age-adjusted PSA, and 12 (15%) had a positive MRI. All 12 patients with an abnormal MRI, and 1 patient with a normal MRI but elevated PSA, underwent prostate biopsy. MRI was the sole indication for biopsy in 6 of the 13 (46%) patients. Eight (10%) patients were diagnosed with prostate cancer (3 BRCA1, 3 BRCA2, 1 ATM, 1 TP53), half of which were grade group ≥2. MRI-based screening did not miss any of the cancers, whereas age-adjusted PSA would have missed 7 of the 8 cancers (included 3 of the 4 grade group ≥2 cancers). CONCLUSIONS: Our early findings suggest prostate cancer is prevalent among men with high-risk germline genetic variants. MRI-based screening may enhance early detection of prostate cancer beyond PSA-based strategies in this patient population. Source of Funding: Prostate Cancer Foundation, Urology Care Foundation © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e549 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Keyan Salari More articles by this author Alexandra Hunter More articles by this author Andrew Amini More articles by this author Aya Almashad More articles by this author Shelley McCormick More articles by this author Linda Rodgers More articles by this author Expand All Advertisement PDF downloadLoading ...

Prostate Biopsy Strategy Integrating Prostate Health Index and Multiparametric Magnetic Resonance Imaging Optimizes the Predictive Value of Clinically Significant Prostate Cancer in Prostate Imaging Reporting and Data System Gray-Zone Imaging

Purpose: The Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI) are used as complementary tools for more accurate diagnosis in men with suspected prostate cancer (PCa). This study investigated whether the combination of PHI and mpMRI better predict clinically significant PCa (csPCa), defined as a Gleason score of ≥7. Materials and Methods: Ninety-four men with clinical suspicion of csPCa were prospectively included. PHI was determined before the prostate biopsy. A uroradiologist reviewed mpMRI findings by using the Prostate Imaging Reporting and Data System version 2.1 (PI-RADS version 2.1). Fusion-targeted biopsy with systematic biopsy was performed in patients with any suspicious lesions on MRI (PI-RADS assessment category ≥3), whereas systematic biopsy was performed in patients without suspicious lesions. The diagnostic values of different biomarkers and PI-RADS were compared by the area under the receiver operating curve (area under the curve [AUC]) for detecting csPCa. Results: Forty-nine (52%) patients were diagnosed with csPCa. The csPCa group had higher median PHI and more abnormal MRI findings than did the non-csPCa group. The median total prostate-specific antigen (PSA) level was similar between the PI-RADS 3 and 4 lesion groups. The median PHI values increased and more patients were diagnosed as having csPCa with an increase in PI-RADS. The receiver operating characteristic curve indicated that PHI and MRI (AUC 0.85 and 0.82, respectively) predicted csPCa more accurately than did the total PSA, free PSA ratio, and PSA density. Adding PHI to mpMRI significantly increased the diagnostic accuracy for csPCa (P = 0.004). PHI remained the optimal biomarker in patients with “gray zone” PI-RADS 3 or PI-RADS 4 lesions. Conclusion: PHI can guide decision-making for prostate biopsy for patients with gray-zone mpMRI lesions. We proposed a biopsy strategy incorporating PHI and MRI which resulted in the avoidance of biopsies in 35% of the patients.

Frontoparietal 18F-FDG-PET hypo-metabolism in Lennox-Gastaut syndrome: Further evidence highlighting the key network

IntroductionLennox Gastaut syndrome (LGS) can be conceptualised as a “secondary network epilepsy”, in which the shared electroclinical manifestations reflect epileptic recruitment of a common brain network, despite a range of underlying aetiologies. We aimed to identify the key networks recruited by the epileptic process of LGS using interictal 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography (18F-FDG-PET). MethodsGroup analysis of cerebral 18F-FDG-PET, comparing 21 patients with LGS (mean age = 15 years) and 18 pseudo-controls (mean age = 19 years), studied at Austin Health Melbourne, between 2004 and 2015. To minimise the influence of individual patient lesions in the LGS group, we only studied brain hemispheres without structural MRI abnormalities. The pseudo-control group consisted of age- and sex-matched patients with unilateral temporal lobe epilepsy, using only the hemispheres contralateral to the side of epilepsy. Voxel-wise permutation testing compared 18F-FDG-PET uptake between groups. Associations were explored between areas of altered metabolism and clinical variables (age of seizure onset, proportion of life with epilepsy, and verbal/nonverbal ability). Penetrance maps were calculated to explore spatial consistency of altered metabolic patterns across individual patients with LGS. ResultsAlthough not always readily apparent on visual inspection of individual patient scans, group analysis revealed hypometabolism in a network of regions including prefrontal and premotor cortex, anterior and posterior cingulate, inferior parietal lobule, and precuneus (p < 0.05, corrected for family-wise error). These brain regions tended to show a greater reduction in metabolism in non-verbal compared to verbal LGS patients, although this difference was not statistically significant. No areas of hypermetabolism were detected on group analysis, although ∼25 % of individual patients showed increased metabolism (relative to pseudo-controls) in the brainstem, putamen, thalamus, cerebellum, and pericentral cortex. DiscussionInterictal hypometabolism in frontoparietal cortex in LGS is compatible with our previous EEG-fMRI and SPECT studies showing that interictal bursts of generalised paroxysmal fast activity and tonic seizures recruit similar cortical regions. This study provides further evidence that these regions are central to the electroclinical expression of LGS.

Clinical features of 28 cases of anti-leucine-rich glioma-inactivated protein 1 encephalitis and anti-contactin-associated protein-like 2 encephalitis.

Autoimmune encephalitis arising from autoantibodies against leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) are rare and with high clinical heterogeneity. They are easily misdiagnosed and missing diagnosed. This study aims to explore the clinical characteristics, auxiliary examinations, therapies and prognosis of anti-LGI1 and anti-CASPR2 encephalitis. Seventeen anti-LGI1 and 11 anti-CASPR2 encephalitis patients who were admitted to the Department of Neurology, Xiangya Hospital, Central South University between January 2018 and January 2021 were collected and retrospectively analyzed. Autoimmune encephalitis related antibodies and paraneoplastic antibodies were screened in all patients. The clinical manifestations, results of laboratory tests, imaging features, treatments and outcomes of 2 encephalitis groups were analyzed and compared. In the anti-LGI1 encephalitis group, the age of 17 patients was 28-83 (53.18±19.08) years old, and the ratio of male to female was 9꞉8. There were 10 patients with cognitive impairment, 7 seizures, 4 faciobrachial dystonic seizures, and 1 psychiatric disturbance. Hyponatremia was observed in 7 patients. Eight patients had increased slow waves and 5 had epileptic discharge in electroencephalogram (EEG). Brain magnetic resonance (MRI) showed T2-weighted imaging (T2WI) and fluid attenuated inversion recovery (FLAIR) hyperintense signal in the temporal lobe, hippocampus and basal ganglia in 13 patients. In the anti-CASPR2 group, the age of 11 patients was 17-68 (47.18±16.20) years old, and the ratio of male to female was 5꞉6, with 7 limbic encephalitis, 1 Morvan syndrome, and 3 acquired neuromyotonia (NMT). Three patients had increased slow waves and 2 had epileptic discharge in EEG. Brain MRI showed T2WI and FLAIR hyperintense signal in the temporal lobe, hippocampus in 2 patients. Steroids, intravenous immunoglobin, and plasma exchange were administrated in 16 anti-LGI1 encephalitis and 8 anti-CASPR2 encephalitis patients with good therapeutic responses. Among them, 1 patient with anti-LGI1 encephalitis and 3 with anti-CASPR2 encephalitis were administrated with mycophenolate mofetil for immune maintenance therapy. No recurrences were observed in all patients with immunotherapy except for 2 patients who lost of follow-up. There were significant differences in cognitive impairment, hyponatremia, and brain MRI abnormalities between anti-LGI1 and anti-CASPR2 encephalitis patients (all P<0.05). Limbic encephalitis is a common syndrome in both anti-LGI1 and anti-CASPR2 encephalitis patients. Anti-CASPR2 encephalitis has a wider clinical spectrum than anti-LGI1 encephalitis, presenting as NMT and Morvan syndrome, which has a closer relationship with tumors. Both of these 2 antibodies associated disorders are sensitive to immunotherapy and have a good prognosis.

The association of intrapartum deceleration and acceleration areas with MRI findings in neonatal encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is an important contributor to disability worldwide. The current cardiotocography (CTG) predictive value for neonatal outcome is limited. To assess the association of intrapartum CTG deceleration and acceleration areas with early MRI cerebral pathology in infants with HIE. Term and near-term low-risk pregnancies that resulted in HIE, treated with therapeutic hypothermia with sufficient CTG records from a single, tertiary hospital between 2013 and 2021 were enrolled. Accelerations and decelerations areas, their minimum and maximum depths, and duration were calculated as well as the acceleration-to-deceleration area ratio during the 120 min prior to delivery. These data were assessed for associations with higher degrees of abnormality on early MRI scans. A total of 77 infants were included in the final analysis. Significant associations between increased total acceleration area (p = 0.007) and between a higher acceleration-to-deceleration area ratio (p = 0.003) and better MRI results were detected. In neonates treated for HIE, acceleration area and acceleration-to-deceleration ratio are associated with the risk of neonatal brain MRI abnormalities. To increase the role of these measurements as a relevant clinical tool, larger, more powered prospective trials are needed, using computerized real-time analysis. The current cardiotocography predictive value for neonatal outcome is limited. This study aimed to assess the association of intrapartum deceleration and acceleration areas with the degree of cerebral injury in early cerebral MRI of neonates with encephalopathy. Lower acceleration area and acceleration-to-deceleration ratio were found to be associated with a higher degree of neonatal brain injury. Brain MRI is a marker of long-term outcome; its association with cardiotocography indices supports their association with long-term outcome in these neonates. Future computer-based CTG area analysis could assist in delivery room decision making to better time interventions and prevent hypoxic-ischemic encephalopathy.

Long-term seizure outcome with the surgically remediable syndrome of frontal lobe epilepsy associated with superior frontal sulcus-related dysplasia.

To assess the long-term outcome of the surgically remediable syndrome of frontal lobe epilepsy (FLE) associated with superior frontal sulcus (SFS)-related dysplasia. We retrospectively reviewed the medical charts and surgical features of 31 patients with drug-resistant frontal lobe epilepsy in our centers between 2016 and 2018. All patients underwent surgical resection. According to the epileptogenic zone (EZ), localization and resection extent were classified as (1) pure SFS group (PS group), (2) associated SFS group (AS group), and (3) no SFS group (NS group). The general characteristics, neuroradiological findings, morbidity, pathology, and long-term seizure outcome after surgery were analyzed to extract the potential value of the surgery for SFS-related dysplasia. Of 31 patients with FLE who underwent epilepsy surgery, 15 patients (nine men) were included PS group, five patients (five men) in the AS group, and 11 patients (eight men) in the NS group. Eleven patients detected abnormal focal signals in the presurgical MRI. Six patients in the PS group demonstrated the suspected focal cortical dysplasia (FCD) in the SFS detected with MRI. All patients demonstrated focal abnormal hypometabolism foci in the PET-MR co-registration. Twenty-five patients (80.6%) were seizure-free since surgery, including all 15 patients (100%) of the PS group, three in five patients (60%) of the AS group, and seven in 11 patients (63.6%) of the NS group. The difference in outcome between different groups was significant (p = 0.004, PS vs. AS group; p = 0.005, PS vs. NS group). As of the last follow-up (mean 66.2 ± 9.7months), 25 patients (80.6%) were seizure-free since surgery (Engel's class I). In addition, antiseizure medication was withdrawn in 19 patients (61.3%). Histologic examination of resected specimens revealed FCD in all 31 patients. The percentage of FCD II type was 100, 60, and 63.6% in the three different groups, respectively. SFS-related dysplasia is a neuropathologic entity with a favorable postoperative outcome. FCD II is the most common type of SFS-related dysplasia. FDG-PET co-registered with MRI should be performed in patients with suspected SFS-related dysplasia, since it may depict areas of hypometabolism suggestive of dysplasia in the absence of MRI abnormalities.

Scurvy, abnormal MRI, and gelatinous bone marrow in an adolescent with avoidant restrictive food intake disorder

BackgroundAlthough medical literature describes pediatric scurvy as “rare”, a growing number of case reports suggests otherwise. Patients often undergo costly and unnecessary workup due to unfamiliarity with the presentation of scurvy. This case report further supports the small yet growing literature documenting scurvy and its manifestations in patients with eating disorders.Case presentationA 15-year-old female presented to the emergency department with bilateral knee and ankle swelling and pain in the setting of chronic lower limb rash and BMI of 16.3. For years, she had restricted her diet to carbohydrates. Exam showed perifollicular petechial hemorrhagic rash with corkscrew hairs, knee edema, ankle edema with restricted range of motion, and antalgic gait. She was admitted for severe malnutrition from avoidant restrictive food intake disorder. Her hospital course was complicated by recurrent normocytic anemia and fever. Hematology workup revealed anemia from iron deficiency, vitamin K deficiency, and anemia of chronic disease. Rheumatology workup was negative. MRI findings showed dark T1 and bright T2 signals and were read as consistent with leukemia/lymphoma, chronic multifocal osteomyelitis, or Langerhans cell histiocytosis. However, bone marrow biopsy showed gelatinous transformation secondary to malnutrition. She was treated with vitamin C and a nutrition plan and her symptoms improved.ConclusionsAlthough this patient had common manifestations of scurvy, including perifollicular petechial hemorrhagic rash, joint effusions, anemia, and recurrent fevers, she still underwent an extensive workup. Clinicians should be aware that scurvy can present with multiple symptoms that mimic infectious, rheumatic, oncologic and hematological disease. Clinicians should have a high index of suspicion for scurvy in patients with malnutrition and eating disorders.

Recessive pathogenic variants in MCAT cause combined oxidative phosphorylation deficiency.

Malonyl-CoA-acyl carrier protein transacylase (MCAT) is an enzyme involved in mitochondrial fatty acid synthesis (mtFAS) and catalyzes the transfer of the malonyl moiety of malonyl-CoA to the mitochondrial acyl carrier protein (ACP). Previously, we showed that loss-of-function of mtFAS genes, including Mcat, is associated with severe loss of electron transport chain (ETC) complexes in mouse immortalized skeletal myoblasts (Nowinski et al., 2020). Here, we report a proband presenting with hypotonia, failure to thrive, nystagmus, and abnormal brain MRI findings. Using whole exome sequencing, we identified biallelic variants in MCAT. Protein levels for NDUFB8 and COXII, subunits of complex I and IV respectively, were markedly reduced in lymphoblasts and fibroblasts, as well as SDHB for complex II in fibroblasts. ETC enzyme activities were decreased in parallel. Re-expression of wild-type MCAT rescued the phenotype in patient fibroblasts. This is the first report of a patient with MCAT pathogenic variants and combined oxidative phosphorylation deficiency.

Prognostic analysis in children with focal cortical dysplasia II undergoing epilepsy surgery: Clinical and radiological factors.

The aim of this study was to investigate the value of clinical profiles and radiological findings in assessing postsurgical outcomes in children with focal cortical dysplasia (FCD) II while exploring prognostic predictors of this disease. We retrospectively reviewed 50 patients with postoperative pathologically confirmed FCD II from January 2016 to June 2021. The clinical profiles and preoperative radiological findings were measured and analyzed. The patients were classified into four classes based on the Engel Class Outcome System at the last follow-up. For the analysis, the patients were divided into two categories based on Engel I and Engel II-IV, namely, seizure-free and non-seizure-free groups. Qualitative and quantitative factors were subsequently compared by groups using comparative statistics. Receiver operating characteristic (ROC) curves were used to identify the predictors of prognosis in children with FCD II. Thirty-seven patients (74%) had Engel class I outcomes. The minimum postsurgical follow-up was 1 year. At the epilepsy onset, patients who attained seizure freedom were older and less likely to have no apparent lesions on the preoperative MRI ("MRI-negative"). The non-seizure-free group exhibited a higher gray matter signal intensity ratio (GR) on 3D T1-MPRAGE images (p = 0.006), with a lower GR on T2WI images (p = 0.003) and FLAIR images (p = 0.032). The ROC curve indicated that the model that combined the GR value of all MRI sequences (AUC, 0.87; 95% CI, 0.77-0.97; p < 0.001; 86% sensitivity, 85% specificity) was able to predict prognosis accurately. A lower age at the onset or the MRI-negative finding of FCD lesions suggests a poor prognosis for children with FCD II. The model consisting of GR values from three MRI sequences facilitates the prognostic assessment of FCD II patients with subtle MRI abnormalities to prevent worse outcomes.

Symptom-imaging correlation in lumbar spine pain.

Lumbar spine MRI is associated with a high prevalence of morphological abnormalities in both symptomatic and asymptomatic individuals. A difficult challenge, therefore, is distinguishing the relevant findings causing symptoms from incidental findings. The accurate diagnosis of pain generator is important because misdiagnosis can negatively impact patient management and outcome. Spine physicians use clinical symptoms and signs to interpret lumbar spine MRI and make treatment decisions. Symptom-MRI correlation enables the targeted inspection of images for pain generator. Radiologists can also use clinical information to improve diagnostic confidence and the value of dictated reports. Because high-quality clinical information may be difficult to obtain, radiologists often generate lists of lumbar spine abnormalities that are otherwise difficult to rank as pain generators. Based on the literature review, this article attempts to distinguish the MRI abnormalities that may represent incidental findings from the abnormalities that are more commonly associated with lumbar spine-related symptoms.

Analysis of specific risk factors of neurodevelopmental disorder in hearing-impaired infants under ten months of age: "EnTNDre" an opening research stemming from a transdisciplinary partnership.

Approximately 20% of children born with severe to profound hearing loss (HL) have an associated disorder that poses a neurodevelopmental risk [1]. The objective of this study is to identify the criteria and profiles of deaf infants at risk of neurodevelopmental disorders (NDD) to provide early intervention. Twenty-two infants aged three to ten months with bilateral congenital deafness were included. Each child attended a consultation with a psychiatrist specializing in the development of hearing-impaired infants as part of their ENT follow-up. The quality of their early development was analyzed using the Olliac grid and well-known postural and sensorimotor criteria. The children were then classified into three groups: normal examination (Group 1), evident NDD (Group 2), and intermediate examination (Group 3). Early medical history, the etiology of deafness, cerebral imaging, and vestibular test results were collected and compared in the different groups. The average age of the children at the time of observation was seven months (3-10 months). All had sensorineural HL, with identified causes in 13 out of 22 cases: five cases of connexin 26 gene mutation, three cases of CHARGE syndrome, two CMV infections, one Usher syndrome, one GATA3 mutation, and one LHPL5 mutation. The average score on the Olliac grid was nine (0-15), and abnormal postural and sensorimotor behaviors were found in 15 cases out of 22 (68%). 27% of the children were classified in Group 1, 45% in Group 2, and 27% in Group 3. Children with non-isolated HL, abnormal brain MRI (8/22), malformations outside the auditory system (10/22), vestibular impairments (9/22), and/or CMV infections (2/22) were distributed as follows: 2/6 in Group 1, 9/10 in Group 2, and 3/6 in Group 3. 8/22 children had suffered perinatal complications (0/6 in Group 1, 6/10 in Group 2, and 2/5 in Group 3). Only one child had a first-degree relative with NDD. He belonged to Group 2. To our knowledge, this paper is the first to describe the development of infants with congenital deafness. It is based on an observation time that had been included in the procedure of multidisciplinary evaluations prior to cochlear implantation (CI), thanks to the partnership between a psychiatric center for deaf children and an ENT-pediatric implantology service. This consultation was aimed at assessing the quality of neurodevelopment and identifying NDD without a specific referral, with good acceptability for families. Using the Olliac grid and postural and sensorimotor criteria developed to be assessed in the routine care consultation, we identified evident early signs of NDD in 45% of infants. This group (Group 2) requires early, targeted, developmental support. Some children in an intermediate zone (Group 3) require further observation and support. The very early identification of NDD seems to be relevant in the care of hearing-impaired infants. The use of the Olliac grid and developmental scales seems relevant to identifying infants at risk for NDD.