The Pattern of Retinal Ganglion Cell Loss in Wolfram Syndrome is Distinct From Mitochondrial Optic Neuropathies.

PURPOSE: To describe the clinical phenotype of a cohort of patients with Wolfram syndrome (WS), focusing on the pattern of optic atrophy correlated with brain magnetic resonance imaging (MRI) measurements, as compared with patients with OPA1-related dominant optic atrophy (DOA). DESIGN: Retrospective, comparative cohort study. METHODS: We reviewed 25 patients with WS and 33 age-matched patients affected by OPA1-related DOA. Ophthalmologic, neurologic, endocrinologic, and MRI data from patients with WS were retrospectively retrieved. Ophthalmologic data were compared with data from patients with OPA1-related DOA and further analyzed for age dependency dividing patients in age quartiles. In a subgroup of patients with WS, we correlated the structural damage assessed by optical coherence tomography (OCT) with brain MRI morphologic measurements. Visual acuity (VA), visual field mean defect (MD), retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness were assessed by OCT and MRI morphologic measurements of anterior and posterior visual pathways. RESULTS: Optic atrophy was present in 100% of patients with WS. VA, MD, and RNFL thickness loss were worse in patients with WS with a faster decline since early age as compared with patients with DOA, who displayed a more stable visual function over the years. Conversely, GCL sectors were overall thinner in patients with DOA since early age compared to patients with WS, in which GCL thickness started to decline later in life. The neuroradiologic subanalysis on 11 patients with WS exhibited bilateral thinning of the anterior optic pathway, especially the prechiasmatic optic nerves and optic tracts. Optic tract thinning was significantly correlated with GCL thickness but not with RNFL parameters. CONCLUSIONS: Our results showed a generally more severe and diffuse degeneration of both anterior and posterior visual pathways in patients with WS, with fast deterioration of visual function and structural OCT parameters since early age. The pattern observed with OCT suggests that retinal ganglion cell axonal degeneration (ie, RNFL) precedes cellular body atrophy (ie, GCL) by about a decade. This differs substantially from DOA, in which a more stable visual function is evident with predominant early loss of GCL, indirectly supporting the lack of a primary mitochondrial dysfunction in patients with WS.

"2-step MCI-AD": a simple scoring system to predict rapid conversion from mild cognitive impairment to Alzheimer dementia.

BACKGROUND: Several techniques are available to identify, among patients with mild cognitive impairment (MCI), those at risk of conversion to Alzheimer dementia (CAD). However, simple cost-effective methods to assess the risk are not available yet. METHODS: This retrospective study included 143 MCI outpatients (76.6±5.2 years, 46.8% women). Baseline variables were common neuropsychological tests (including Mini Mental State Examination-MMSE and Montreal Cognitive Assessment-MoCA), brain CT and 18F-fluorodeoxyglucose (FDG)-PET. Outcome variable was CAD after 1 year. RESULTS: At follow-up, 31 (21.7%) patients had CAD. In multivariable analysis (OR, 95% CI), female sex (4.7, 1.6-14.0), MoCA-executive component <3 (6.3, 2.1-19.2), left medial temporal atrophy (MTA) ≥3 (5.4, 1.9-15.7) and FDG-PET suggesting CAD (5.4, 1.9-15.7) were associated with CAD (area under ROC curve 0.873). Without FDG-PET, MMSE score <28 remained associated with CAD (6.0, 2.2-16.9). As first step (before FDG-PET execution), we counted 1 point for MMSE <28, executive MoCA <3 and left MTA ≥3. With 2-3 points CAD probability was high (75%) and with 0 points it was low (6.5%). Thus, FDG-PET (second step) might be performed only in patients with 1 point (probability 19.7%, 42.7% of patients). Among them, 35% had a positive FDG-PET, suggesting high risk. Overall, 28.0% of patients were considered at high risk (specificity 83.9%, sensitivity 71.0%, accuracy 81.1%). CONCLUSION: With a 2-step procedure, less than half of MCI patients might undergo FDG-PET and nearly a quarter of our patients was found to be at high CAD risk, including almost three quarters of future CADs.

3D Reconstruction and physical renal model to improve percutaneous punture during PNL

ABSTRACT Introduction and Objectives: We aim to present the use of 3D digital and physical renal model (1-5) to guide the percutaneous access during percutaneous nephrolithotripsy (PNL). Materials and Methods: We present the clinical case of a 30 years old man with left renal stone (25x15 mm). A virtual 3D reconstruction of the anatomical model including the stone, the renal parenchyma, the urinary collecting system (UCS) and the skeletal landmarks (lumbar spine and ribs) was elaborated. Finally, a physical 3D model was created with a 3D printer including the renal parenchyma, UCS and the stone. The surgeon evaluated the 3D virtual reconstruction and manipulated the printed model before surgery to improve the anatomical knowledge and to facilitate the percutaneous access. In prone position, combining ultrasound and fluoroscopy implemented by the preoperative anatomical planning based on the 3D virtual and printed model, an easy and safe access of the inferior calyx was achieved. Then, the patient underwent PNL using a 30 Fr Amplatz sheet with semi-rigid nephroscope and ultrasound energy to achieve a complete lithotripsy of the pelvic stone. Results: The procedure was safely completed with 1 single percutaneous puncture (time of puncture 2 minutes). Overall surgical time was 90 min. No intra and postoperative complications were reported. The CT scan performed before discharge confirmed a complete stone free state. Conclusion: The 3D-guided approach to PNL facilitates the preoperative planning of the puncture with better knowledge of the renal anatomy and may be helpful to reduce operative time and improve the learning curve.

Clinical Features and Pathophysiology of Disorders of Arousal in Adults: A Window Into the Sleeping Brain.

Introduction: Disorders of Arousal (DoA) are NREM parasomnias that have been typically regarded as self-limited childhood manifestations. It is now clear that DoA can persist in adults, often presenting with distinctive characteristics. So far, few studies have described the clinical course and characteristics of DoA in adulthood, therefore a large part of their semiology is ignored. The aim of this study is to describe the clinical manifestations of DoA in an adult population and to provide a pathophysiological interpretation of their features. Methods: We screened our database for all 1,600 adult (≥15 years) patients with sleep-related motor behaviors between 1995 and 2016. We identified 45 patients with typical DoA episodes, of whom a complete history, neurological examination and diagnostic video-polysomnography (VPSG) were available. All patients provided a detailed description of their episodes (with particular regards to semiology, frequency, and association with stressful life events) in different life periods. VPSG recordings were reviewed and DoA episodes were identified and assigned to three different categories according to their complexity. Results: Our population was composed of 45 adult patients ranging between 15 and 76 years. Sleepwalking was reported by 86% of patients, possibly associated with complex interactions with the environment and violent behaviors in 53% of cases; distressing mental contents were reported by 64%. Recall of the episodes was reported in 77% of patients. Non-restorative sleep was reported in 46% of patients. Stress was a potential episode trigger in 80% of patients. VPSG recordings documented 334 DoA episodes. According to our classification of motor patterns, 282 episodes (84%) were Simple Arousal Movements (SAMs), 34 (10%) Rapid Arousal Movements (RAMs) and 18 (5%) Complex Arousal Movements (CAMs). Discussion: Our study confirms that DoA in adulthood present with distinctive characteristics, such as non-restorative sleep, violence and complex, or bizarre behaviors. Alternative classifications of DoA based on motor patterns could be useful to characterize DoA episodes in adults, as different motor patterns often coexist in the same individual and minor episodes are more common but generally underreported by patients. Prospective studies are needed for a definitive characterization of DoA in adulthood throughout the life course.

Dominant intraprostatic lesion boosting in sexual-sparing radiotherapy of prostate cancer: A planning feasibility study.

AIM: Radical radiotherapy of prostate cancer requires a relatively high dose to achieve an optimal tumor control probability and a reduced dose to the critical structures related to the sexual function (S_OARs) in order to avoid erectile dysfunction. The aim of this study was to perform a planning feasibility analysis of a 3-level dose prescription with Simultaneous Integrated Boost (SIB) on the dominant intraprostatic lesion (DIL) and with S_OARs sparing. MATERIAL AND METHODS: Twelve patients with clinically localized intermediate risk prostate cancer were included. The prostate, seminal vescicles, and DIL Clinical Target Volumes were delineated on rigid fused MRI-CT simulation images using mp-MRI as a separate guide. A 5 mm margin was added to define the PTVs. Penile bulb (PB), corpora cavernosa (CC), internal pudendal arteries (IPAs) and neurovascular bundles were contoured as S_OARs. The following doses were prescribed in 25 fractions: 56.25 Gy to PTVsv, 67.50 Gy to PTVp, and 75 Gy to PTVdil. Standard plans (SD-VMAT) were created to fulfil targets coverage and Quantec constraints for conventional OARs (SD_OARs: rectum, bladder, and femoral heads). For each patient, a new "sexual-sparing" plan (SS-VMAT) was created adding new objectives for S_OARs with priority to minimize mean doses to IPAs, CC, and PB. Dose-volume histogram end points were compared between the 2 plans using Wilcoxon test. RESULTS: D98% were >95% of prescribed doses for all targets and techniques. No significant differences were found in sparing SD_OARs for considered metrics. Regarding S_OARs, SS_VMAT plans provided a significant reduction of the dose. Mean dose reduction for IPAs, CC, PB, and neurovascular bundles was 32.4% (11.2 Gy, p = 0.002), 22.5% (4.1 Gy, p = 0.006), 10.0% (4.6 Gy, p = 0.010), and 2.6% (1.8 Gy, p = 0.020), respectively. CONCLUSIONS: We showed that a significant dose sparing for S_OARs using VMAT-SIB strategy is feasible allowing "sexual-sparing" and highly conformal plans with dose escalation to the DIL.

New hallmark of hepatocellular carcinoma, early hepatocellular carcinoma and high-grade dysplastic nodules on Gd-EOB-DTPA MRI in patients with cirrhosis: a new diagnostic algorithm.

OBJECTIVE: Many improvements have been made in diagnosing hepatocellular carcinoma (HCC), but the radiological hallmarks of HCC have remained the same for many years. We prospectively evaluated the imaging criteria of HCC, early HCC and high-grade dysplastic nodules (HGDNs) in patients under surveillance for chronic liver disease, using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and diffusion-weighted imaging. DESIGN: Our study population included 420 nodules >1 cm in 228 patients. The MRI findings of each nodule were collected in all sequences/phases. The diagnosis of HCC was made according to the American Association for the Study of Liver Diseases (AASLD) criteria; all atypical nodules were diagnosed using histology. RESULTS: A classification and regression tree was developed using three MRI findings which were independently significant correlated variables for early HCC/HCC, and the best sequence of their application in a new diagnostic algorithm (hepatobiliary hypointensity, arterial hyperintensity and diffusion restriction) was suggested. This algorithm demonstrated, both in the entire study population and for nodules ≤2 cm, higher sensitivity (96% [95% CI 93.5% to 97.6%] and 96.6% [95% CI 93.9% to 98.5%], P<0.001, respectively) and slightly lower specificity (91.8% [95% CI 88.6% to 94.1%], P=0.063, and 92.7% [95% CI 88.9% to 95.4%], P=0.125, respectively) than those of the AASLD criteria. Our new diagnostic algorithm also showed a very high sensitivity (94.7%; 95% CI 92% to 96.6%) and specificity (99.3%; 95% CI 97.7% to 99.8%) in classifying HGDN. CONCLUSION: Our new diagnostic algorithm demonstrated significantly higher sensitivity and comparable specificity than those of the AASLD imaging criteria for HCC in patients with cirrhosis evaluated using Gd-EOB-DTPA MRI, even for lesions ≤2 cm. Moreover, this diagnostic algorithm allowed evaluating other lesions which could arise in a cirrhotic liver, such as early HCC and HGDN.

Specific motor patterns of arousal disorders in adults: a video-polysomnographic analysis of 184 episodes.

OBJECTIVE: To compile an objective accurate description of the motor patterns of adult arousal disorders (ADs). METHODS: We reviewed 59 nocturnal video-polysomnographic (VPSG) recordings of 30 adult patients (>15 years) with a history of sleepwalking (SW). We scrutinized the semeiology of all 184 episodes recorded, classifying them into three groups according to three semeiological motor patterns characterized by increasing intensity and complexity: simple arousal movements (pattern I), characterized by head flexion/extension, head flexion/extension and limb movement or head flexion/extension and partial trunk flexion/extension; rising arousal movements (pattern II), characterized by a complete trunk flexion with patient sitting up in bed; and complex arousal with ambulatory movements (pattern III) characterized by SW. The VPSG recordings were compared to those of 10 healthy controls. RESULTS: AD patients presented with 169 pattern I, 37 pattern II, and nine pattern III episodes. Pattern I developed into pattern II in 17 cases and into pattern II followed by pattern III in five patients. Pattern II developed into pattern III in four patients. Onset was abrupt in 55% of the episodes. Episodes lasted a mean (±standard deviation) of 33 ± 35 s. Movements tended to halt temporarily during 72% of the episodes. We recorded 248 movements during sleep in the healthy controls, none of whom presented with AD patterns. CONCLUSION: We identified three specific motor patterns in AD patients not previously reported and not observed in healthy controls. Identification of these patterns could be important for diagnosis and serve as the basis for a new definition of AD in adults.