Secondary Atrophy Research Articles

Retinal telangiectasia-like lesions in a 15-year-old female with Hereditary hemorrhagic telangiectasia – a case report

BackgroundHereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome is a bleeding disorder that can affect all parts of the body including the eyes. Different ocular abnormalities have been described in relation to HHT, but the pathogenesis of retinal involvement is still unknown. A few cases have described chorioretinal abnormalities primarily occurring in elderly patients. In this study, we present a unique case of a young female with known HHT and a series of retinal fundus images including optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) with macular telangiectasia-like lesions.Case presentationA young female genetically diagnosed with hereditary hemorrhagic telangiectasia (HHT), is regularly attending retinal screening since she is diagnosed with Type 1 diabetes. At one visit, abnormal retinal telangiectasia-like lesions in the macula, are observed. These abnormalities are monitored over an extended period of time with fundus imaging, and further investigated with OCT and OCTA. The patient has no visual complaints at any time and best-corrected visual acuity is 20/20 Snellen equivalent in both eyes.ConclusionsTo the best of our knowledge, this is the first case to describe the occurrence of telangiectasia-like lesions in macula with secondary choriocapillaris atrophy in a patient diagnosed with HHT in such a young age.

CLINICAL AND RADIOLOGICAL PROFILE OF PATIENTS OF IDIOPATHIC INTRACRANIAL HYPERTENSION PATIENTS ATTENDING TERTIARY CARE HOSPITAL IN SOUTH INDIA

Background: idiopathic intracranial hypertension (IIH) is one of the causes of headache presenting in tertiary hospital. However, there are only limited studies on IIH. : To study the clinical and radiological prole of IIH patients. hospital based observationalAim Setting and Design: descriptive study. Headache patients were admitted and evaluated in the department of Neurology (from April 2021 toMaterial and Methods: April 2022) detailed history, clinical examination, and neuroimaging, Cerebral spinal uid (CSF)routine analysis and manometry were done. After evaluation, diagnosed 32 cases of IIH by modied Dandy criteria and the secondary causes of raised intracranial pressure and primary ocular pathology were excluded. Entire study population were females. The mean age was 30 years. 16 (50%) cases were obese, 9 overweightResults: and normal BMI were seven. All case has Headache, bifrontal headache was very common rather than occipital as presentation. Bilateral papilledema seen in all except one case of secondary optic atrophy with equivalent nding in Optical Coherent tomography. CSF analysis was normal and CSF pressure was elevated(≥250mmg) in all cases. Empty Sella was the most common radiological nding (26/32; 81.25%). Conclusion: IIH typically affects females of childbearing age group, mostly obese. However, it is not uncommon in the nonobese female as seen in the present study. In Indian subcontinent overweight and obesity may not be a dominant risk factor for the development of IIH. Cases with normal BMI with clinical features of raised intracranial pressure, refractory headache, visual symptoms and normal neuroimaging or empty Sella on MRI should be evaluated for IIH

Evolving Hypothesis that Prostate/BPH Size Matters in Protection against Prostate Cancer

Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two predominant urologic diseases affecting aging men. As a matter of fact, 95–98% of elderly men with prostate as their “primary organ disease” for consulting urologists have either the clinical diagnosis of BPH, PCa or both. Other primary diagnoses of the prostate such as sarcoma, lymphoma or isolated bacterial prostatitis (not in the context of a systemic urinary tract infection) are rare entities. Although BPH and PCa are very common, their interaction is currently not well understood. Numerous clinical studies and meta-analysis reviews have demonstrated a negative correlation between prostate BPH size and the probability of PCa presence, but little is known to explain this clinical phenomenon. Recent histo-anatomical and magnetic resonance imaging studies have revealed data leading to a hypothesis indicating the expanding transition zone (TZ) in a growing BPH prostate causes mechanical stress within the peripheral zone (PZ) with secondary fibrosis and atrophy of the glands within the PZ. This dynamic interaction of the TZ against the PZ in a growing BPH-prostate could explain the negative correlation between BPH size and PCa incidence. The purpose of this review is to present and discuss the evolving hypothesis that prostate size may matter and be protective against prostate cancer.

A Rare Presentation Characterized by Epileptic Spasms in ALDH7A1, Pyridox(am)ine-5'-Phosphate Oxidase, and PLPBP Deficiency.

Objective: To analyze the clinical feature, treatment, and prognosis of epileptic spasms (ES) in vitamin B6–dependent epilepsy, including patients with pyridoxine-dependent epilepsy (PDE) caused by ALDH7A1 mutation, pyridox(am)ine-5′-phosphate oxidase (PNPO) deficiency, and PLPBP deficiency. Methods: We analyzed data from a cohort of 54 cases with PDE, 13 cases with PNPO deficiency, and 2 cases with PLPBP deficiency and looked for the presentation of ES among them. Results: A total of 11 patients with the seizure presentation of ES have been collected. Among them, four patients carried mutations in ALDH7A1, six carried mutations in PNPO, and the remaining one carried mutation in PLPBP. The analysis of this cohort identified nine cases presenting as infantile spasms distributed in the three diseases and two cases presenting as Ohtahara syndrome diagnosed with PDE and PNPO deficiency, respectively. In the PDE and PLPBP deficiency groups, seizures were controlled by pyridoxine monotherapy, and the remaining one had refractory seizures due to secondary brain atrophy. In the groups with PNPO deficiency, one patient showed seizure-free when treated by PLP combined with valproic acid, three still had infrequent seizures treated by PLP monotherapy or pyridoxine or PLP combined with other antiseizure medications, and two died. In two cases presenting as Ohtahara syndrome, after regular treatment, one showed seizure-free, the others showed a marked decrease in seizure frequency, and they both showed an improvement in EEG. Significance: ES might be a common form of seizures in PNPO deficiency, and EEG presented as hypsarrhythmia or a burst suppression pattern. It is difficult for pyridoxine to control frequent seizures caused by secondary brain injury. In our PNPO deficiency cohort, patients with infantile spasms did not respond better to PLP than pyridoxine. Timely and correct treatment could prevent the transformation of the child’s disease from Ohtahara syndrome and infantile spasms to subsequent epileptic encephalopathy or refractory epilepsy.

Other Hereditary Syndromes Associated with Secondary Optic Atrophy

Optic neuropathy is a cause that seriously impairs vision loss, which we frequently encounter in ophthalmology practice. Although it is frequently seen with eye diseases such as glaucoma, it can also be seen together with systemic neurodegenerative syndromes. In this review, we have included some rare syndromes that cause genetically inherited optic atrophy. In these syndromes, the structure of the encoded proteins is disrupted as a result of mutated genes. The cellular disorder is reflected in the phenotype by affecting the related intracellular chemical reaction.

Visual outcomes and factors predictive of visual loss in Behcet's disease in Sultan Qaboos University Hospital, Oman

This study aimed to evaluate the visual outcomes and associated factors in Omani patients with Behcet's disease (BD). This is a descriptive retrospective analytical cohort study. All Omani patients of age 5-65 years with a confirmed clinical diagnosis of BD having ocular manifestation who attended the Rheumatology and Ophthalmology clinics at Sultan Qaboos University Hospital, Oman from January 2018 to October 2020. The demographic data, clinical findings, systemic, and ocular examination of all the recruited patients were retrieved from the electronic patient record. The study included 31 male and 16 female participants. The median age is 29.7 ± 10.6 years. Most patients with ocular manifestations presented in the third decade of their life (21-30 years' age). The most common ocular manifestations in our study were uveitis (91.5%) followed by vitritis (40.4%), and retinal vasculitis (36.2%). The most common ocular complications in order of frequency were cataract (27.7%), posterior synechiae (23.4%), and cystoid macular edema (21.2%). In this study, 22.7% of the patients with BD-related ocular manifestations reported severe visual loss. In addition, when adding the patients with severe visual loss secondary to complications such as secondary glaucoma and optic nerve atrophy, the severe visual loss cumulatively reported being 50% for both groups. The clinical characteristics of ocular manifestations in BD in Oman are similar to data from studies that have been conducted in other countries. However, our study found that the severity of ocular manifestations was more dominant among females. This study finding can be helpful for clinicians to predict ocular manifestations of BD to plan a timely follow-up and subsequently prevent further severe complications or visual loss.

Clinical and Functional Characteristics of Secondary Geographic Atrophy Against the Background of Exudative Age-Related Macular Degeneration

Background.Studies demonstrate the need for long-term follow-up of patients with wet age-related macular degeneration (AMD) treated with inhibitors of angiogenesis to monitor long-term vision outcomes and assess the safety of antiangiogenic therapy in relation to the risk of secondary geographic atrophy.
 Aims to determine the characteristic clinical and functional signs of secondary GA that developed against the background of wet AMD.
 Methods.In 22 patients (25 eyes) with wet AMD and 18 healthy subjects comparable in age and sex standard ophthalmological and instrumental studies were performed and photopic electroretinograms (ERGs) were recorded according to ISCEV standards, flicker-ERGs, multifocal ERGs and electrooculogram.
 Results.The appearance of the area of secondary atrophy against the background of wet AMD in eyes treated with inhibitors of angiogenesis is clinically indistinguishable from areas of geographic atrophy that developed as an outcome of dry AMD. The ERG-signs of secondary atrophy are described, which are similar to the biomarkers of primary atrophy and specifically differ from them. Secondary atrophy is characterized by the dependence of the increase in the b/a ratio on the atrophic area, reducing of the 8.3 Hz-flicker-ERG amplitude in the absence of 24 Hz-flicker ERG changes. In eyes with secondary atrophy, a significant decrease in the density of the multifocal ERG P1-peak was shown not only in the first hexagon but also in the parafoveal zone. The electrooculography results showed a sharper dark troughs decrease in with an increase in Ardens ratio in patients with secondary atrophya on the background of wet AMD, in contrast to the previously described changes in primary geographic atrophy.
 Conclusion.Comparison of the change in the b/a ratio with secondary atrophy area in patients with wet AMD may have clinical implications for assessing retinal dysfunction and predicting visual function. Secondary atrophy is associated with a pronounced inhibition of photoreceptor activity with better preservation of cone bipolar cells. The ERG and electrooculography data taking together indicate a more significant dysfunction of the retinal pigment epithelium in GA against the background of wet AMD and the associated deterioration of photoreceptor function than the changes characterizing primary geographic atrophy.

Profile of disc atrophy in Cipto Mangunkusumo National Hospital

Disc atrophy is the end stage of the degeneration of the optic nerve. It is divided into primary and secondary disc atrophy. This study aimed to describe the etiologies and the characteristics of disc atrophy in Neurology Outpatient Clinic, Cipto Mangunkusumo Hospital, Jakarta.

English

BACKGROUND In developing countries like India, it is essential to spread awareness about cataract and its complications like lens induced glaucoma, uveitis. Lens induced glaucoma (LIG) can lead to irreversible blindness due to secondary optic atrophy. The purpose of this study was to stress on early diagnosis and timely management in preventing blindness due to lens induced glaucoma in patients visiting ESIC Medical College and Hospital, Gulbarga. Karnataka. METHODS This retrospective descriptive type of statistical study was conducted in the Department of Ophthalmology, ESIC Medical College and Hospital, Gulbarga. Karnataka, from March 2018 to March 2021. Intraocular pressure (IOP) and visual acuity was recorded in all patients after through history taking, ocular examination and fundoscopy. After subjecting for exclusion criteria, cases of LIG were confirmed and included in the study. RESULTS In our study we found total 25 cases having LIG, in that 9 were male patients (36 %) and 16 were females (64 %). Phacomorphic glaucoma was recorded in 19 patients (76 %) and phacolytic glaucoma in 5 cases (20 %). Intraocular pressure of 40 - 49 mmHg was recorded in 16 patients (64 %) followed by 30 – 39 mmHg in 5 patients (20 %) and 50 – 59 mmHg in 4 patients (16 %). In our study, 13 patients had visual acuity of counting fingers (CF) 3 meters to 5 meters (52 %) followed by 6/60 to 6/24 (20 %) and hand movements to counting fingers 3 metres in (12 %) and one patient had no perception of light (4 %). All patients underwent cataract surgery with intraocular implantation under local anaesthesia. After 2 weeks of follow up, vision restored was between 6/9 - 6/18 (40 %) in 10 patients followed by 6/18 - 6/60 (28 %) in 7 patients and no improvement in vision in one patient. CONCLUSIONS Glaucoma is one of the causes for irreversible blindness. Though overall prevalence is less than 5 % but gets its one of major contribution from lens induced glaucoma. One good thing about LIG is patient presents early due to loss of vision and pain, so if we intervene with early diagnosis and manage patients, vision can be restored successfully. KEYWORDS LIG, Cataract, IOP, Phacomorphic Glaucoma, Photolytic Glaucoma

Infratentorial MRI Findings in Rasmussen Encephalitis Suggest Primary Cerebellar Involvement.

Background and ObjectiveRasmussen encephalitis (RE) is characterized by its unilateral cerebral involvement. However, both ipsi- and contralesional cerebellar atrophy have been anecdotally reported raising questions about the nature and extent of infratentorial findings. Using MRI, we morphometrically investigated the cerebellum and hypothesized abnormalities beyond the effects of secondary atrophy, implicating a primary involvement of the cerebellum by RE.MethodsVoxel-based morphometry of the cerebellum and brainstem was conducted in 57 patients with RE and in 57 matched controls. Furthermore, patient-specific asymmetry indices (AIs) of cerebellar morphometry and fluid-attenuated inversion recovery (FLAIR) intensity were calculated. Using diffusion tensor imaging, the integrity of the cortico-ponto-cerebellar (CPC) tract was assessed. Finally, a spatial independent component analysis (ICA) was used to compare atrophy patterns between groups.ResultsPatients with RE showed bilateral cerebellar and predominantly ipsilesional mesencephalic atrophy (p < 0.01). Morphometric AIs revealed ipsilesional < contralesional asymmetry in 27 and ipsilesional > contralesional asymmetry in 30 patients. In patients with predominant ipsilesional atrophy, morphometric AIs strongly correlated with FLAIR intensity AIs (r = 0.86, p < 0.0001). Fractional anisotropy was lower for ipsilesional-to-contralesional CPC tracts than opposite tracts (T = 2.30, p < 0.05). ICA revealed bilateral and strictly ipsi- and contralesional atrophy components in patients with RE (p < 0.05).DiscussionWe demonstrated atrophy of the ipsilesional-to-contralesional CPC pathway and, consequently, interpret the loss of contralesional gray matter as secondary crossed cerebellar atrophy. The ipsilesional cerebellar atrophy, however, defies this explanation. Based on FLAIR hyperintensities, we interpret ipsilesional atrophy to be due to inflammation in the scope of a primary involvement of the cerebellum by RE.

Expert consensus and operational guidelines on exercise rehabilitation of chronic obstructive pulmonary disease with integrating traditional Chinese medicine and Western medicine.

Chronic obstructive pulmonary disease (COPD) has become a widespread global chronic respiratory disease. In view of the large patient population, high mortality and disability rate, and heavy medical burden, COPD has become a major challenge for public health worldwide. According to epidemiological studies and demographic data, the prevalence of COPD in China is 13.7% and the number of COPD patients has reached more than 100 million. Therefore, it is of considerable significance to make more efforts to prevent and treat COPD (1). COPD is a chronic respiratory disease with dyspnea as its main clinical manifestation, especially during physical activity. COPD is often associated with cardiovascular, motor, metabolic and other systemic diseases, and may lead to pathological changes in many other systems (2). Muscle dysfunction is the most common extrapulmonary change that may influence the skeleton and respiratory muscles. Muscle dysfunction can lead to amyotrophy, muscle weakness, and other symptoms, which influence the skeletal muscle most significantly and result in poor exercise tolerance in patients (3). The pathological changes in skeletal muscle and dyspnea reduce the participation of activities in COPD patients and cause secondary muscle atrophy. These factors can result in declining motor ability, which is the critical predictor of mortality in COPD patients (4). COPD can influence patients’ health and quality of life. Delaying disease progression, alleviating symptoms, improving psychological status, and enhancing quality of life are the main goals of medical interventions for COPD patients. Pulmonary rehabilitation, as an indispensable part of effective treatments, is a multidisciplinary management program targeted at COPD patients to control disease progression, improve quality of life, and reduce the hospitalization rate (5). Exercise treatment, as the core of rehabilitation programs, has a higher degree of evidence in pulmonary rehabilitation that can improve dyspnea symptoms, increase motor abilities, and be helpful for improving psychological disorders and enhancing quality of life (3,6,7). To better guide exercise rehabilitation treatment for COPD patients, and to provide a systematic and operational plan for community doctors, pulmonary doctors and other health care providers on rehabilitation treatment, evaluation, treatment and follow-up, an expert group on respiratory rehabilitation and a professional committee on respiratory rehabilitation of the China Medical Education Association formed a common understanding by searching domestic and foreign studies, consulting with experts, and discussion. This consensus is based on existing research to develop a declarative document, focusing on the feasibility of our current clinical reality. In clinical practice, we still need to consider each patient’s specific situation to design individualized exercise rehabilitation programs. We present the following article in accordance with the RIGHT reporting checklist (available at https://dx.doi.org/10.21037/jtd-21-431).

Abstract P359: Secondary Thalamic Atrophy Related to Brain Infarction is Associated With Post-Stroke Cognitive Impairment

Background: The thalamus is globally connected to many brain regions. Previous work highlights thalamic contributions to multiple cognitive functions, but few studies have measured thalamic volume changes or explored correlates of such changes with post-stroke cognition. Hence this study investigates possible associations of thalamic volumes with post-stroke cognitive functions. Methods: Participants with brain infarcts (6-42 months) underwent volumetric brain MRI and cognitive testing, including the Montreal Cognitive Assessment (MoCA). Focal Brain infarcts and thalami were traced manually. If the patient had bilateral infarcts, the side of the primary infarct volume defined the hemisphere involved. Brain parcellation and volumetrics used our comprehensive semi-automatic brain region and vascular lesion extraction pipeline (Ramirez, Neuroimage, 2011). MRI in 24 age and gender-matched healthy people provided normal comparative thalamic volumes. Thalamic atrophy was defined by percent thalamic volume loss in the stroke hemisphere compared to the other side. Spearman correlation assessed relationships between thalamic and infarct volumes and MoCA scores. Logistic regression analysis assessed whether thalamic atrophy correlated with MoCA score. Results: Thalami volumes ipsilateral to the infarct in stroke patients (n=55) were smaller than left (4.4 ± 1.4 vs. 5.4 ± 0.8 cc, p = 0.012) and right (4.4 ± 1.4 vs. 5.3 ± 0.7 cc, p = 0.024) thalamic volumes in the controls. Thalamic volumes were inversely correlated with ipsilateral infarct volumes (r = -0.384, p = 0.004). After controlling for head-size and brain atrophy, infarct volume independently correlated with ipsilateral thalamic volume s (β= -0.068, P=0.026), and only frontal infarcts (β = 2.300, p = 0.021) independently contributed to &gt; 15% ipsilateral thalamic atrophy. Left thalamic atrophy of &gt; 10% correlated significantly with poorer MoCA performance (β = 3.139, p = 0.023), after controlling for demographics and infarct volumes. Conclusions: Our results suggest that remote effects of infarction on ipsilateral thalamic volume, presumably related to disrupted thalamic-cortical interconnectivity, is associated with a commonly used metric of post-stroke cognitive impairment.

Histological Assessment of Wallerian Degeneration of the Rat Tibial Nerve Following Crush and Transection Injuries.

Wallerian degeneration (WD) following peripheral nerve injury (PNI) is an area of growing focus for pharmacological developments. Clinically, WD presents challenges in achieving full functional recovery following PNI, as prolonged denervation of distal tissues for an extended period of time can irreversibly destabilize sensory and motor targets with secondary tissue atrophy. Our objective is to improve upon histological assessments of WD. Conventional methods utilize a qualitative system simply describing the presence or absence of WD in nerve fibers. We propose a three-category assessment that allows more quantification: A fibers appear normal, B fibers have moderate WD (altered axoplasm), and C fibers have extensive WD (myelin figures). Analysis was by light microscopy (LM) on semithin sections stained with toluidine blue in three rat tibial nerve lesion models (crush, partial transection, and complete transection) at 5 days postop and 5 mm distal to the injury site. The LM criteria were verified at the ultrastructural level. This early outcome measure was compared with the loss of extensor postural thrust and the absence of muscle atrophy. The results showed good to excellent internal consistency among counters, demonstrating a significant difference between the crush and transection lesion models. A significant decrease in fiber density in the injured nerves due to inflammation/edema was observed. The growth cones of regenerating axons were evident in the crush lesion group. The ABC method of histological assessment is a consistent and reliable method that will be useful to quantify the effects of different interventions on the WD process.

Correlation between White Matter Hyperintensities Related Gray Matter Volume and Cognition in Cerebral Small Vessel Disease

Background and AimThe relationship between severity of cerebral small vessel disease, as defined by white matter hyperintensities classification, and gray matter volume of different brain regions has not been well defined. This study aimed to investigate brain regions with significant differences in gray matter volume associated with different degrees of white matter hyperintensities in patients with cerebral small vessel disease. Meanwhile, we examined whether correlations existed between gray matter volume in different brain regions and cognitive ability. Methods110 cerebral small vessel disease patients underwent 3.0T Magnetic resonance imaging scans and neuropsychological cognitive assessments. White matter hyperintensities of each subject was graded according to Fazekas grade scale and was divided into two groups: (A) White matter hyperintensities score of 1–2 points (n = 64), (B) White matter hyperintensities score of 3–6 points (n = 46). Gray matter volume was analyzed using voxel-based morphometry implemented in Statistical Parametric Mapping 12 software. ResultsBrain regions with significant differences in gray matter volume between groups were diffused throughout the brain. Patients with high white matter hyperintensities scores exhibited decreased gray matter volume in some subregions of the frontal lobes, the temporal lobes, the parahippocampal gyrus, hippocampus and thalamus (p < 0.05). Among them, gray matter volume in the ventrolateral area of right inferior temporal gyrus, together with the right posterior parietal and occipital thalamus were positively correlated with Montreal Cognitive Assessment scores (p < 0.05). Gray matter volume in the extreme ventrolateral area of right inferior temporal gyrus along with the entorhinal cortex of left parahippocampal gyrus were positively correlated with both Montreal Cognitive Assessment and Mini-Mental Status Examination scores (p < 0.05). ConclusionsCerebral small vessel disease is considered as a whole brain disease and local white matter lesions can influence the gray matter in remote areas. Reducing the severity and progression of white matter hyperintensities may help to prevent secondary brain atrophy and cognitive impairment.

Prostatic artery embolization with polyethylene glycol microspheres: evaluation in a canine spontaneous benign prostatic hyperplasia model

BackgroundProstatic artery embolization (PAE) is a minimally invasive technique for the management of symptomatic benign prostatic hyperplasia (BPH) relieving the lower urinary tract symptoms in patients. Various embolic agents have been tested in animal models and subsequently used in human patients. The purpose of this study was to evaluate the technical feasibility, effectiveness, and safety of PAE with polyethylene glycol microspheres in a canine spontaneous BPH model.ResultsFive adult male Beagle dogs (4.78 ± 1.11 years) were diagnosed by tranrectal ultrasonography of spontaneous BPH (prostate volume > 18 ml) and underwent PAE with polyethylene glycol microspheres (400 ± 75 μm). PAE procedures were performed successfully in all dogs. After PAE, all dogs were inspected for potential procedure-related complications during 1 month of follow-up. No major complications were observed any animal. Follow-up angiography was performed in each animal at 1 month of follow-up. Recanalization was demonstrated in all the embolized prostatic arteries or main branches at the end of the study. Magnetic Resonance Imaging (MRI) evaluations were performed immediately before PAE as baseline data, and 1 week, 2 weeks and 1 month after PAE. MRI study showed that the prostate shrank substantially with ischemic necrosis in each dog. There was a significant reduction in the mean prostate volume at 2 weeks and 1 month compared with the baseline data, from 19.95 ± 1.89 mL to 13.14 ± 2.33 and 9.35 ± 2.69 mL (p < 0.001), respectively. Histopathological study was conducted after 1-month follow-up angiography and confirmed the therapeutic responses with diffuse glandular atrophy and interstitial fibrosis.ConclusionsThe findings of the present study support that PAE with the use of polyethylene glycol microspheres is a safe and feasible procedure that may induce a significant shrinkage of prostate due to the local ischemia and secondary glandular atrophy. Early recanalization of target arteries remains to be further addressed in both laboratory investigation and clinical practice.

Dorsal lumbotomy for pediatric upper pole hemi-nephrectomy: Back (door) to the future?

Upper pole heminephrectomy (UHN) is performed for two main indications in children: ectopic ureterocele and duplication anomalies with upper pole ectopy, both in the context of a poorly functioning upper pole moiety. Current popular techniques for conducting UHN include laparoscopic (LPN) and robot-assisted laparoscopic (RAPN). To evaluate outcomes following dorsal lumbotomy (DL), an open approach used historically for pyeloplasty and pyelolithotomy, and in which no clinical trials or exclusive case-series have been conducted for upper pole hemi-nephrectomy (UHN) in children. We ultimately aim to compare our outcomes following DL at our centre to that of published outcomes of minimally invasive approaches to UHN. Institutional board review was obtained (H18-03716) for a retrospective review of 50 UHN performed in 49 consecutive pediatric patients using the DL approach by a single surgeon between 2001 and 2019. Clinical variables and indicators included age, sex, weight, skin-to-skin time, total operating room time, duration of hospital stay, post-operative complications, analgesic requirements, and post-operative ultrasound results. Of 50 UHN performed, 23 had a presurgical diagnosis of ectopic ureter, and 27 ureterocele. Mean weight of patients was 12.61kg, and the mean age at surgery was 24.55 months. Mean (range) for time between skin incision and closure was 88.5 (62-132) minutes, and the mean (range) total operating room time was 138.5 (70-180) minutes. There were neither intraoperative complications nor transfusions. The mean (range) post-operative opioid delivered was 0.73 (0.00-2.00) mg/kg/day. Mean (range) post-operative ibuprofen delivered was 5.41 (0.00-37.73) mg/kg/day. Median length of hospital stay was 2 days. No patient received post-operative prescriptions for narcotics at discharge. There were no wound complications. One patient had secondary atrophy of the lower pole. Secondary lower tract surgery, unrelated to surgical approach, was performed in five patients. Ten patients experienced a urinary tract infection at some point after surgery. DL is safe, feasible, and produces operative outcomes and times comparable to that of laparoscopic and robotic techniques. These findings as well as operative costs should be considered when selecting a surgical technique for UHN.

Intramuscular Brown Fat Activation Decreases Muscle Atrophy and Fatty Infiltration and Improves Gait After Delayed Rotator Cuff Repair in Mice

Background: Successful repair of large and massive rotator cuff (RC) tears remains a challenge at least partially because of secondary muscle atrophy and fatty infiltration. β3 Adrenergic agonists are a group of drugs that promote fat resorption through “white fat browning” of intramuscular stem cells. Purpose: To test the role of a β3 adrenergic receptor agonist, amibegron, in improving muscle quality and forelimb function in a delayed RC repair model via promoting brown/beige adipose tissue activation. Study Design: Controlled laboratory study. Methods: Three-month-old PDGFRα-GFP reporter mice, wild type C57BL/6J mice, and uncoupling protein 1 (UCP-1) knockout mice underwent unilateral supraspinatus tendon transection with a 6-week delayed tendon repair. Animals with sham surgery served as controls. Amibegron was given either immediately after tendon transection or after repair. Gait analysis was conducted to measure forelimb function at 6 weeks after tendon repair. Animals were sacrificed at 6 weeks after repair. Supraspinatus muscles were harvested and analyzed histologically. Reverse transcription polymerase chain reaction was performed to quantify gene expression related to atrophy, fibrosis, and fatty infiltration. Results: Histology of PDGFRα reporter mice showed significantly increased UCP-1 expression, suggesting white fat browning in muscle after RC repair. As administered either immediately after tendon transection or after tendon repair, amibegron significantly reduced muscle atrophy and fatty infiltration and resumed normal upper extremity gait in wild type mice. However, the effect of amibegron was not present in UCP-1 knockout mice, suggesting that the effect of amibegron in treating RC muscle atrophy and fatty infiltration is through a UCP 1–dependent mechanism. Conclusion: Amibegron reduced muscle atrophy and fatty infiltration and improved forelimb function after delayed RC repair through a UCP 1–dependent mechanism. This may be an effective clinical treatment strategy for patients to improve muscle quality after RC repair. Clinical Relevance: β3 Adrenergic agonists may serve as a new pharmacologic modality to treat RC muscle atrophy and fatty infiltration to improve clinical outcome of RC repair.

Genetic and clinical findings of panel-based targeted exome sequencing in a northeast Chinese cohort with retinitis pigmentosa.

BackgroundPanel‐based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa.MethodsA total of 87 subjects, comprising 23 probands and their family members (total patients: 32) with confirmed retinitis pigmentosa were recruited in the study. Panel‐based targeted exome sequencing was used to sequence the patients and family members, all subjects with retinitis pigmentosa underwent a complete ophthalmologic examination.ResultsOf the 23 probands, the clinical manifestations include night blindness, narrowing of vision, secondary cataracts, choroidal atrophy, color blindness, and high myopia, the average age of onset of night blindness is 12.9 ± 14 (range, 0–65; median, 8). Posterior subcapsular opacities is the most common forms of secondary cataracts (nine cases, 39.1%), and peripheral choroidal atrophy is the most common form of secondary choroidal atrophy (12 cases, 52.2%). Of these probands with complication peripheral choroidal atrophy, there were eight probands (66.7%, 8/12) caused by the pathogenic variation in USH2A gene. A total of 17 genes and 45 variants were detected in 23 probands. Among these genes, the commonest genes were USH2A (40%; 18/45), RP1 (15.6%; 7/45), and EYS (8.9%; 4/45), and the top three genes account for 56.5% (13/23) of diagnostic probands. Among these variants, comprising 22 (48.9%) pathogenic variants, 14 (31%) likely pathogenic variants, and nine (20%) uncertain clinical significance variants, and 22 variants was discovered first time. Most of the mutations associated with RP were missense (53.3%, 24/45), and the remaining mutation types include frameshift (35.6%, 16/45), nonsense (6.7%, 3/45), and spliceSite (4.4%, 2/45). Among the probands with mutations detected, compound heterozygous forms was detected in 13 (56.5%, 13/23) probands, and digenic inheritance (DI) forms was detected in five (21.7%, 5/23) probands.ConclusionPanel‐based targeted exome sequencing revealed 23 novel mutations, recognized different combinations forms of variants, and extended the mutational spectrum of retinitis pigmentosa and depicted common variants in northeast China.

Abstract WP476: Remarkable Hemorrhagic Imaging Manifestations Might Be Responsible for the Prominent Atrophy and Cognitive Decline in Sneddon Syndrome

Objective: Sneddon syndrome is a rare non-inflammatory arteriopathy affecting small and medium-sized arteries, characterized by a generalized livedo reticularis and recurrent ischemic stroke. Hemorrhagic stroke was reported in limited cases, but microbleeds and superficial siderosis were rarely issued, which might be underdiagnosed due to the limitation of technique. We aimed to investigate the hemorrhagic imaging features of Sneddon syndrome and explore the possible mechanism and clinical relevance. Methods: Clinical data and cerebral MR imaging including T2* sequence of 6 consecutive patients with Sneddon syndrome were reviewed. Results: The most common neurological manifestations were cognitive impairment and stroke attack(66.7%), followed by seizures(33.3%) and movement disorder(16.7%). Cerebral microbleeds were detected in all the patients on T2* sequence,four of whom presented more than 5 microbleeds.The majority of the microbleeds were predominantly cortical restricted and especially located in the cortical watersheds. Multiple superficial siderosis were identified and mainly involved cortical watersheds in 5 cases. Significant cerebral atrophy with prominent secondary white matter hyperintensities in bilateral cortical watersheds were also observed. Abnormal tortuous and multiple focal occlusion of bilateral distal MCA were shown in 1 patient by DSA. No stenosis of proximal segment of cerebral arteries was detected in all the patients. Conclusions: This is the first report illustrating abundant cortical microbleeds and superficial siderosis mainly involved the anterior and posterior cortical watersheds in Sneddon syndrome. The surprisingly identical topographic distribution of hemorrhagic lesions and the corresponding obvious atrophy suggest cerebral atrophy might be secondary to the microangiopathy related hemorrhagic lesions and further contribute to the neurological deficit, especially the early cognitive decline in Sneddon syndrome,although further investigation is needed to elucidate the precise underlying pathogenesis. These highlight cortical microbleeds and superficial siderosis located in cortical watershed and the secondary atrophy in youth might be highly indicative of Sneddon syndrome.

Outcome of Endoscopic third Ventriculostomy for Obstructive Hydrocephalus due to Posterior Fossa Lesions

Background and purpose: Obstructive hydrocephalus can be treated with External ventricular Drainage (ETV), Ventriculo peritoneal shunt insertion, upfront tumor removal without cerebrospinal fluid diversion procedures or more recently ETV. Aim of our study was to study the outcome of ETV in treating such patients.&#x0D; Material and method: Descriptive observational study conducted at Upendra Devkota Memorial Institute Of Neurological and Allied Sciences from Sep 2015 to may 2017.&#x0D; Result: Twenty-three patients met the inclusion criteria. Among which, 14 (39%) patients were male with male to female ratio of 1.55. We included wide age range from 3 years to 68 years. Seven patients (30.4%) were less than 10 years while 6 patients (23%) were above 60 years old. Patients with Posterior fossa presented with varied symptoms. Ten patients (43.4%) presented with decreased level of consciousness, 14 (60.8%) presented with visual symptoms, 17 (73.9%) presented with vomiting and 23 (100%) presented with headache (Figure. 3). Visual acuity was normal among 3 (13%), decreased among 11 (48%) and with no perception of light among 3 (13%). However, acuity was not assessed among 6 (26%) patients (Figure 4).Funduscopic evaluation revealed papilledema among 20 (87%) patients while secondary optic atrophy among 3 (13%) patients. Patients were evaluated in follow up for symptomatic improvement. Consciousness were improved among 8 (80%) patients, visual symptoms improved among 10 (71.4%) patients, vomiting subsided among 15 (88.2%) patients while headache improved among 100%. Following ETV, 5 (21.7%) patients developed complications, 3 (13%) patients had intraventricular bleeding while 2 (8.6%) patients had CSF leakage from the wound.&#x0D; Conclusion: Endoscopic third ventriculostomy is a relatively safe and valid option for treatment obstructive hydrocephalus due to posterior fossa lesions.