Comprehensive Workup Research Articles

Bilateral lower limb weakness due to transverse myelitis as a first presentation of ankylosing spondylitis

Abstract: The occurrence of transverse myelitis (TM) in ankylosing spondylitis (AS) patients is a rarely reported event with only a few reports of similar cases in existing literature. When faced with a patient with TM, attention should be focused on determining the cause. AS should be kept in mind as a possible etiology. We report the case of a 58-year-old female patient who presented at Al-Ahli Hospital in Palestine, with a 3-day history of lower limb weakness, preceded by a 1-month history of lower back pain with radiation to lower limbs. Based on clinical findings and a comprehensive diagnostic work-up, the patient was diagnosed with TM along with AS. Steroid therapy was started, with pulse therapy having minimal effect. Due to the poor response to steroid therapy, plasmapheresis was done with a good response. After careful consideration, our patient was discharged on low-dose oral glucocorticoids for her TM, and methotrexate for her AS, with close follow-up by a neurologist and a rheumatologist.

Isolated Hypoglossal Nerve Palsy: A Rare Complication of Organophosphate Poisoning

Abstract Purpose: This case report aims to describe a rare manifestation of isolated hypoglossal nerve palsy (HNP) resulting from organophosphate poisoning (OP), specifically organophosphate- induced delayed neuropathy (OPIDN). The primary objective of this case report is to highlight this unusual manifestation and discuss its potential underlying mechanisms, emphasizing the importance of timely diagnosis and appropriate management. Case Report: A 31-year-old male with a history of consuming a commercial chlorpyrifos formulation presented with acute organophosphate poisoning symptoms that improved with appropriate treatment. However, two weeks later, the patient developed neurological deficits (numbness and weakness spreading from the plantar region to the upper limbs) involving the hypoglossal nerve, manifesting as left-sided tongue deviation, fasciculation, and atrophy, resulting in speech and swallowing difficulties. A comprehensive workup ruled out other potential causes of HNP, supporting the link between OPIDN and isolated HNP. Despite regaining limb strength, the patient’s speech and swallowing issues persisted, prompting a follow-up visit to our hospital for further management and rehabilitation. Conclusion: This case report highlights a unique manifestation of OPIDN, resulting in isolated HNP, a rare phenomenon. The correlation between exposure to chlorpyrifos, acute organophosphate poisoning, and delayed onset of HNP suggests a causative relationship. Prompt diagnosis, appropriate treatment, and timely speech and swallowing rehabilitation are vital for optimizing outcomes in such cases. Further research is needed to understand the mechanisms underlying this selective vulnerability of OPIDN and to develop targeted interventions.

Primary left atrial rhabdomyosarcoma in a 42-year-old patient: an unusual cardiac tumor presentation

Left atrial rhabdomyosarcoma is an extremely rare and often overlooked form of primary cardiac malignancy that primarily affects the atria of the heart. The aggressive nature of atrial rhabdomyosarcoma necessitates early recognition, a comprehensive diagnostic workup, and prompt intervention to achieve the best possible outcomes. In this case report, we present the clinical details of a 42-year-old female diagnosed with left atrial rhabdomyosarcoma, who exhibited symptoms of recent pulmonary edema, weight loss, and alternating flushing. Diagnosis, surgical treatment, and the iatrogenic atrial septal defect complication due to interatrial septum invasion were discussed.

Diphteric Myocarditis: A Case Report on Ecg and Cardiac Imaging Findings with the Levels of Cardiac Enzymes in a 17-Year-Old

Background: Diphtheria, caused by Corynebacterium diphtheriae, remains a life-threatening infectious disease in regions with low vaccination uptake. Myocarditis, a severe cardiac complication of diphtheria, is a leading cause of mortality. Despite the success of vaccines in reducing diphtheria cases, sporadic cases continue to occur, leading to significant health complications. Objective: This case report aims to present the clinical course, electrocardiogram (ECG) and cardiac imaging findings, and serial levels of serum troponin in a 17-year-old patient with diphtheritic myocarditis, and to discuss the management and outcomes. Methods: This study was conducted at Lady Reading Hospital, Peshawar, Pakistan. Ethical approval was obtained from the hospital's ethical review board, and informed consent was acquired from the patient and guardians. A comprehensive diagnostic workup was performed, including clinical examination, laboratory tests, ECG, transthoracic echocardiography (TTE), and cardiac magnetic resonance imaging (MRI). The patient’s vital signs, blood pressure, pulse rate, and jugular venous pressure were recorded. Laboratory tests included leukocyte count, erythrocyte sedimentation rate (ESR), and serial serum troponin measurements. ECG findings were documented, and TTE was used to assess left ventricular ejection fraction (LVEF). Cardiac MRI was performed to identify myocardial edema and delayed enhancement. Treatment included intravenous diuretics, ACE inhibitors, SGLT2 inhibitors, benzylpenicillin, and corticosteroids. Data were analyzed using SPSS version 25.0. Results: The patient presented with a blood pressure of 110/70 mmHg and a pulse rate of 88 bpm. Initial laboratory tests showed a normal leukocyte count, ESR of 45 mm/hr, and troponin levels of 25 ng/ml, which decreased to 21.85 ng/ml and then to 8 ng/ml. ECG revealed ST segment depressions in the precordial leads. TTE showed an initial LVEF of 50%, declining to 35% and then to 28% within a week. Post-treatment, LVEF improved to 44% and subsequently to 55% at four weeks. Cardiac MRI indicated myocardial edema in the apical anterior and apical septal walls, with intramyocardial and subepicardial delayed enhancement. Conclusion: Diphtheritic myocarditis can lead to rapid and severe deterioration of cardiac function. Early diagnosis and aggressive treatment, including the use of advanced imaging techniques and comprehensive medical therapy, can result in significant improvement in cardiac function and patient outcomes. Public health initiatives to improve vaccination coverage are essential to prevent such life-threatening complications.

Congenital hallux valgus occurs in Fibrodysplasia Ossificans Progressiva and BMPR1B-associated dysplasia: an important distinction

BackgroundFibrodysplasia Ossificans Progressiva (FOP; OMIM #135100) is an ultrarare genetic disorder characterised by congenital bilateral hallux valgus (CBHV), intermittent soft tissue swellings and progressive heterotopic ossification. We report a three-month-old girl with great toe abnormalities similar to FOP, in whom comprehensive clinical workup and genetic investigations illustrates an alternative diagnosis.Case presentationA three-month-old girl presented with CBHV. The antenatal period was unremarkable, she was born by spontaneous vaginal delivery with an uneventful subsequent course, except for maternal concern of her bent toes which received reassurance from several health professionals. Her mother’s persisting concerns were explored via the internet and social media leading her to request referral to an expert bone centre for consideration of FOP. On examination, she was thriving, there was no dysmorphism, subcutaneous lumps, skeletal or extra-skeletal deformity except for shortened great toes with lateral deviation of the proximal and distal phalanges. FOP was a feasible diagnosis, for which CBHV is highlighted as an early sign. A cautionary potential diagnosis of FOP was counselled, including advice to defer intramuscular immunisations until genetic results available. Genetic investigation was undertaken through rapid whole genomic sequencing (WGS), with analysis of data from a skeletal dysplasia gene panel, which demonstrated no ACVR1variants. The only finding was a heterozygous variant of unknown significance in BMPR1B (c1460T>A, p.(Val487Asp)), which encodes a bone morphogenic receptor involved in brachydactyly syndromes A1, A2 and D and acromesomelic dysplasia 3 (only the latter being an autosomal recessive condition).ConclusionThis report highlights that CBHV serves as a vital diagnostic indicator of FOP and affected infants should be considered and investigated for FOP, including precautionary management whilst awaiting genetic studies. The second educational aspect is that CBHV may not represent a generalised skeletal disorder, or one much less significant than FOP. Receptor-ligand BMP and Activins mediated interactions are instrumental in the intricate embryology of the great toe. Recognition of non-FOP conditions caused by alterations in different genes are likely to increase with new genomic technology and large gene panels, enhancing understanding of bone signaling pathways.

Long-term risk assessment in athletes with ventricular arrhythmias: the key roles of arrhythmia morphology, complexity, and substrate

Abstract Background Ventricular arrhythmias (VAs) are an important source of concern among athletes. Purpose To determine the prognostic role of non-invasive and invasive diagnostic assessments among athletes with complex VAs. Methods We included 215 athletes (83% male; 28 [19-43] years) with complex VAs in a prospective, multi-center cohort study. At baseline, each athlete underwent a prespecified comprehensive diagnostic workup, which included cardiac magnetic resonance (CMR) in 202 subjects, and electrophysiology study (EPS)/electroanatomical mapping (EAM) in 190. The primary study endpoint was the occurrence of sudden death or sustained VAs during long-term follow-up. Results During a median follow-up of 6.2 (4.4-8.1) years, 16 (7%) athletes had a primary outcome event, including one sudden cardiac death. In univariable Cox models, sustained VAs at presentation (p<0.001), uncommon VA morphology(p=0.004), syncope(p=0.005), abnormal ECG (p=0.003), VAs induction/persistence at exercise testing(p=0.021), late gadolinium enhancement (LGE;p=0.006), low-voltage areas (p=0.003) and late potentials (p<0.001) at EAM, and sustained VA induction by EPS (p<0.001) were all associated with increased risk of primary outcome events. The association of late potentials and EPS inducibility with primary outcome events was confirmed after controlling for all non-invasive predictors at univariable analysis, and the incorporation of findings of invasive tests allowed improved prediction of primary outcome events over clinical/non-invasive findings in isolation (log-likelihood ratio for nested models, p=0.043). Younger age (p=0.032), being a professional athlete (p=0.006), and absence of LGE (p=0.029) were independently associated with higher odds of uninterrupted competitive sports practice until last follow-up. Conclusions A comprehensive diagnostic assessment integrating clinical/ECG findings with CMR and EPS/EAM in selected cases may provide important prognostic information among athletes with complex VAs.

Arrhythmic mitral valve prolapse with versus without prior mitral valve repair: clinical profiles, electrophysiological substrates, and long-term clinical outcomes

Abstract Background Arrhythmic mitral valve prolapse (AMVP) is characterized by an arrhythmogenic left ventricular substrate, with high prevalence of myocardial scar. Whether patients with prior mitral valve repair for mitral valve prolapse (MVP) and new-onset complex ventricular arrhythmias (VAs) after cardiac surgery have different electroanatomical substrate and arrhythmic outcomes compared with AMVP patients without prior mitral valve surgery is currently unknown. Purpose We sought to compare the electroanatomical substrate and long-term clinical outcomes of patients with new-onset complex VAs after mitral valve surgery to AMVP patients without prior surgery. Methods We conducted a multicenter, prospective, observational study, enrolling MVP patients with prior mitral valve repair and new-onset complex VAs (>1000 premature ventricular contractions [PVCs]/day, nonsustained ventricular tachycardia [NSVT], and sustained VT) after cardiac surgery (group A,n=9), and patients with MVP, complex VAs and no prior surgery (group B,n=20). Each patient underwent a comprehensive diagnostic workup, including left ventricular electroanatomical mapping. Clinical-imaging data, as well as the location and segmental extension of both low-voltage areas and late potentials were assessed and compared between the two groups. The primary outcome was the occurrence of sustained VT or ventricular fibrillation(VF) during follow-up. Results In group A, complex VAs were first diagnosed after a median of 30(8-56) months following mitral valve repair. The characteristics of patients from the two study groups are presented in the Table. Patients from group A were older, sustained VT was nonsignificantly more common at baseline, the PVC count nonsignificantly higher, and LVEF nonsignificantly lower. Mitral annular disjunction was never observed in group A, while it was found in 7 patients from group B (p=0.066). At LV electroanatomical voltage mapping, bipolar and unipolar low-voltage areas (LVAs) were equally common in the two groups overall, and typically involved basal perimitral regions. However, patients from group B had concomitant bipolar and unipolar LVAs 50% of times, with larger unipolar LVAs, while patients from group A mostly showed isolated bipolar LVAs. Over a median follow-up of 15 (12-41) months, patients from group A (n=3, 33%) had slightly higher incidence of sustained VT or VF (HR: 1.91; 95% CI, 1.06-42.65; log-rank p=0.02, Figure) than patients from group B (n=2, 10%). Conclusion Compared to patients with AMVP and no prior cardiac surgery, patients with new-onset complex VAs after mitral valve repair for MVP have a slightly different clinical profile and electroanatomical substrate, characterized by predominant bipolar LVAs in the perimitral region. The long-term risk of major ventricular arrhythmias appears slightly higher in MVP patients with prior mitral valve surgery, mandating at least an equally careful risk assessment in both groups.

Abstract PO4-02-07: Prevalence of distant metastases in High-Risk Operable Breast Cancer (HROBC) pT1-2 N2a orhigher at diagnosis

Abstract Introduction: Current standard guidelines do not recommend a routine staging workup in early breast cancer as incidence of de novo metastasis is only 1-2%. Some of these patients are found to have a higher axillary nodal burden after surgery. This prospective study evaluated the incidence of distant metastases in clinically high-risk operable breast cancer (HROBC) who have a higher nodal burden on histopathological report after surgery. The intent was to detect presence of subclinical distant disease that may have an impact on treatment offered and outcome. Currently, there is no compelling data to support a routine metastatic workup in these patients. Methodology: A single-centre study approved by Institutional Ethics Committee was carried out enrolling early breast cancer patients with high nodal burden (four or more axillary nodes positive) after definitive surgery. The HROBC group was defined as early breast cancer patients with pT1/2, N2a/N3 stage on surgical histopathology. They underwent a comprehensive metastatic workup, including ultrasound abdomen, bone scan, and CT scan (thorax-abdomen-pelvis) or PET scan before starting their adjuvant treatment. Burden of distant disease was classified into oligometastatic (M1o) or polymetastatic disease (M1p). The adjuvant treatment intent was redefined as curative or palliative based on the distant disease burden and treatment was modified accordingly. Result: The study accrued 100 HROBC women with pT1-2, pN2a-3 stage disease during 2015-2018 operated upfront for early breast cancer cT1-2 N0-1, of which 97 were included in final analysis. The 3 excluded patients had their surgery elsewhere with clinical diagnosis of early breast cancer with histopathology indicating heavy nodal burden; 2 of them had T3 tumor and 1 had cN3 disease and were deemed a higher stage and would anyway warrant a metastatic work-up and hence were ineligible for the study. Forty percent women were premenopausal, 54 (55.6%) had pN2a disease and 43 (44.4%) had pN3. Staging investigations identified distant metastatic disease (M1) in 8 of 97 women (8.24%). Interestingly, 5 of them had oligometastatic (M1o) disease (5.15%) and 3 had polymetastatic (M1p) disease (3.09%). Between the 2 nodal groups, no specific distribution of M1o or M1p disease was observed, but the pickup rate of overall distant disease was higher in pN3 (11.4%) as against N2a (5.6%) patients p=NS. The most common sites of metastases observed was bone (5/8) followed by liver (3/8). There was no correlation with ER, PgR or HER2neu status and extent of distant disease. The patients with M1o disease, completed their adjuvant treatment as planned along with treatment of oligometastatic sites. Only 3.09% patients who were detected with M1p disease, were treated with a palliative systemic therapy. Conclusion: Early detection of metastatic disease, M1o and M1p, in clinical HROBC could lead to improved treatment strategies. The findings have the possibility to optimize management of high-risk early breast cancer as a separate clinical entity, requiring staging post hoc after primary surgery, for adequate resource stratification and better outcomes, especially in those with 10 or more axillary nodes positive for metastases. This subset may get identified in the TNM classification for better understanding and management. Citation Format: Vani Parmar, Naveena Kumar AN, Basila Ameer Ali, Nita Nair, Shalaka Joshi, Purvi Thakkar, Garvit Chitkara, Varsha Gaikwad, Vaibhav Vanmali, Shabina Siddique, Palak Popat, Sneha Shah, Sangeeta Desai, Tanuja Shet, Meenakshi Thakur, Venkatesh Rangarajan, Rajendra Badwe. Prevalence of distant metastases in High-Risk Operable Breast Cancer (HROBC) pT1-2 N2a orhigher at diagnosis [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-02-07.

Pulmonary Arterial Hypertension (PAH) Group 1 (Part A): Overview, Classification, Clinical Subsets, and Workup

Abstract: Pulmonary hypertension is a rare, progressive disease characterized by increased pulmonary arterial pressure and right ventricular failure due to pulmonary vascular remodeling. The disease definition and management have evolved over time. The 6th WSPH now defines it as a mean pulmonary arterial pressure >20mmHg, while recent ESC/ERS guidelines recommend lowering the threshold for pulmonary vascular resistance to 2WU. : Understanding of the disease has improved through registries, classifying it into five distinct groups with similar histology, pathophysiology, and therapeutic approaches. These groups include PAH, with heritable and idiopathic causes, as well as various clinical subsets involving connective tissue disease, HIV, portopulmonary hypertension, congenital heart disease, and schistosomiasis. Long-term responders to calcium channel blockers, PAH with venous/capillaries involvement, and persistent PH of newborns are categorized under Group 1, now re-classified as IPAH. : A comprehensive workup for suspected patients includes various tests like electrocardiogram, pulmonary function testing, autoimmune workup, HIV testing, echocardiogram, right heart catheterization, and cardiopulmonary exercise testing. : This review emphasizes the disease's definition and epidemiology, delving into each subset and providing updated workup guidelines. The subsequent article will focus on risk stratification and treatment strategies.

SARS-CoV-2 vaccine-associated basilar artery thrombosis and GBS require comprehensive workup and specific therapy.

SARS-CoV-2 vaccine-associated basilar artery thrombosis and GBS require comprehensive workup and specific therapy.

Long-term outcomes of patients with embolic stroke of undetermined source according to subtype

The prognosis of patients with embolic stroke of undetermined source (ESUS) may vary according to the underlying cause. Therefore, we aimed to divide ESUS into subtypes and assess the long-term outcomes. Consecutive patients with acute ischemic stroke who underwent a comprehensive workup, including transesophageal echocardiography and prolonged electrocardiography monitoring, were enrolled. We classified ESUS into minor cardioembolic (CE) ESUS, arteriogenic ESUS, two or more causes ESUS, and no cause ESUS. Arteriogenic ESUS was sub-classified into complex aortic plaque (CAP) ESUS and non-stenotic (< 50%) relevant artery plaque (NAP) ESUS. A total of 775 patients were enrolled. During 1286 ± 748 days follow-up, 116 major adverse cardiovascular events (MACE) occurred (4.2 events/100 patient-years). Among the ESUS subtypes, CAP ESUS was associated with the highest MACE frequency (9.7/100 patient-years, p = 0.021). Cox regression analyses showed that CAP ESUS was associated with MACE (hazard ratio 2.466, 95% confidence interval 1.305–4.660) and any stroke recurrence (hazard ratio 2.470, 95% confidence interval, 1.108–5.508). The prognosis of ESUS varies according to the subtype, with CAP ESUS having the worst prognosis. Categorizing ESUS into subtypes could improve patient care and refine clinical trials.

Vessel wall imaging in the diagnosis of antiphospholipid syndrome presenting as Moyamoya syndrome-A case report.

Objectives: We describe a case of anti-phospholipid syndrome (APLS) vasculopathy presenting with Moyamoya syndrome (MMS) and show the associated intracranial vessel wall MRI (VWI) findings. Methods: A 37-year-old-woman presented with acute onset dizziness and left-sided weakness. Neurologic exam revealed a left facial droop and left hemiparesis. She underwent a comprehensive laboratory work-up for stroke. Neuroimaging included a CT head, CT angiogram, VWI, and digital subtraction angiography. Results: Work-up revealed a triple-positive APLS antibody profile. CT of the head showed an acute right basal ganglia infarction and right frontal subarachnoid hemorrhage. CT angiogram revealed severe stenosis of the right internal carotid artery terminus in a Moyamoya pattern. Intracranial VWI showed long-segment concentric vessel wall thickening and homogeneous vessel wall enhancement and T2-hyperintense wall edema of the stenotic right ICA terminus, M1 middle cerebral artery, and A1 anterior cerebral artery. She was treated with long-term anticoagulation with warfarin and a right superficial temporal artery to middle cerebral artery bypass. Discussion: We present intracranial VWI features of vessel wall pathology in a patient with primary APLS presenting with MMS.

The expectations and experiences of patients regarding the diagnostic workup at a specialized memory clinic: An interview study.

Because of the shift towards earlier diagnosis of dementia and/or Alzheimer's disease (AD), increasing numbers of individuals with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are seen in memory clinics. Yet, evidence indicates that there is room for improvement when it comes to tailoring of the diagnostic work-up to the needs of individual patients. To optimize the quality of care, we explored patients' perspectives regarding the diagnostic work-up at a specialized memory clinic. This interview study was conducted at Karolinska University Hospital (Sweden). The comprehensive diagnostic work-up for dementia at the memory clinic in Solna is conducted within 1 week. A sample of 15 patients (8 female; mean age = 61 years [range 50-72]; 11 SCD, 1 MCIand 3 AD dementia) was purposively selected for a series of three semistructured interviews, focussing on (1) needs and expectations (during the week of diagnostic testing), (2) experiences (within 2 weeks after test-result disclosure)and (3) reflections and evaluation (3 months after disclosure). Transcribed audio-recorded data were analyzed using thematic content analysis (using MaxQDA software). Three key themes were identified: (1) the expectations and motivations of individuals for visiting the memory clinic strongly impacted their experience; (2) the diagnostic work-up impacted individuals psychosocially and (3) the diagnostic work-up provided an opportunity to motivate individuals to adopt a healthier lifestyle. Our findings underscore the importance of enquiring about the expectations and needs of individuals referred to a specialized memory clinic, allowing for expectation management and personalization of provided information/advice, and potentially informing the selection of patients in need of a comprehensive diagnostic work-up. Structural guidance might be needed to support those with SCD and MCI to help them cope with uncertainty, potentially resolve their issues, and/or stimulate brain health. We gathered the perspectives of 15 individuals who had been referred to the memory clinic at three different time points through semistructured interviews, and these interviews were the primary data source.

Evaluating the comprehensive diagnosis efficiency of lung cancer, including measurement of SHOX2 and RASSF1A gene methylation

Methylation of the promoters of SHOX2 and RASSF1A (LungMe®) exhibits promise as a potential molecular biomarker for diagnosing lung cancer. This study sought to assess the aberrant methylation of SHOX2 and RASSF1A in broncho-exfoliated cells (BEC) and compare it with conventional cytology, histology examination, immunohistochemistry, and serum tumor markers to evaluate the overall diagnostic efficiency for lung cancer. This study recruited 240 patients, including 185 malignant cases and 55 benign cases. In our observation, we noted a slight reduction in the detection sensitivity, however, the ΔCt method exhibited a significant enhancement in specificity when compared to Ct judgment. Consequently, the ΔCt method proves to be a more appropriate approach for interpreting methylation results. The diagnostic sensitivity of cytology and histology was in ranged from 20.0%-35.1% and 42.9%-80%, respectively, while the positive detection rate of LungMe® methylation ranged from 70.0% to 100%. Additionally, our findings indicate a higher prevalence of SHOX2( +) among patients exhibiting medium and high expression of Ki67 (P < 0.01), as opposed to those with low expression of Ki67, but RASSF1A methylation did not show this phenomenon (P = 0.35). Furthermore, CEA, SCCA, and CYFRA21-1 showed positive detection rates of 48.8%, 26.2%, and 55.8%, respectively. Finally, we present a comprehensive lung cancer diagnostic work-up, including LumgMe® methylation. The combined analysis of SHOX2 and RASSF1A methylation serves as a powerful complement and extension to conventional methods, enhancing the accuracy of a lung cancer diagnosis with satisfactory sensitivity and specificity.

Bruns Garland Syndrome as the first presentation of type 2 diabetes: two case reports and a practical approach to diagnosis

BackgroundDiabetes is a global health problem causing a significant burden on the healthcare systems both due to the disease itself and associated complications. Diabetic radiculoplexus neuropathies or Bruns–Garland syndrome constitutes a rare form of microvascular complications, more commonly affecting the lumbosacral plexus and, very rarely, the cervical plexus. We describe two Sri Lankan males who presented with diabetic lumbosacral radiculoplexus neuropathy and diabetic cervical radiculoplexus neuropathy as the initial manifestation of diabetes.Case descriptionCase 1: a 49-year-old Sri Lankan hotel chef presented with subacute painful weakness and wasting of the left upper arm for 3 months and weight loss. Left upper limb proximal muscles were wasted with diminished power and reflexes. A nerve conduction study showed comparative amplitude reduction. An electromyogram revealed positive sharp waves, frequent fibrillations, and high amplitude polyphasic motor unit potentials with reduced recruitment in proximal muscles of left upper limb. Case-2: a 47-year-old Sri Lankan carpenter presented with subacute progressive asymmetrical painful weakness and wasting of bilateral thighs for 5 months and weight loss. Lower limb proximal muscles were wasted with reduced power and knee jerks. The nerve conduction study was normal. The electromyogram was similar to case 1 involving both quadratus femoris muscles, which was more prominent on the left side. The work up for an underlying etiology revealed only elevated fasting blood glucose and HbA1c, suggesting a new diagnosis of diabetes associated with neurological symptoms. Patient 1 was diagnosed with diabetic cervical radiculoplexus neuropathy and patient 2 with diabetic lumbosacral radiculoplexus neuropathy. Both showed significant improvement following optimization of glycemic control together with symptomatic treatment and physiotherapy.ConclusionDiagnosis of diabetic radiculoplexus neuropathy requires a comprehensive workup to rule out other sinister pathologies. This case report has a dual importance; it describes diabetic radiculoplexus neuropathy as the very first manifestation of two previously healthy people, giving rise to a new diagnosis of diabetes and, at the same time, reporting on diabetic cervical radiculoplexus neuropathy, which is extremely rare and has never been previously reported in Sri Lanka.

Historic characteristics and mortality of patients in the Swiss Amyloidosis Registry.

Systemic amyloidoses are rare protein-folding diseases with heterogeneous, often nonspecific clinical presentations. To better understand systemic amyloidoses and to apply state-of-the-art diagnostic pathways and treatment, the interdisciplinary Amyloidosis Network was founded in 2013 at University Hospital Zurich. In this respect, a registry was implemented to study the characteristics and life expectancy of patients with amyloidosis within the area covered by the network. Patient data were collected retrospectively for the period 2005-2014 and prospectively from 2015 onwards. Patients aged 18 years or older diagnosed with any subtype of systemic amyloidosis were eligible for inclusion if they were treated in one of the four referring centres (Zurich, Chur, St Gallen, Bellinzona). Baseline data were captured at the time of diagnosis. Follow-up data were assessed half-yearly for the first two years, then annually. Between January 2005 and March 2020, 247 patients were screened, and 155 patients with confirmed systemic amyloidosis were included in the present analysis. The most common amyloidosis type was light-chain (49.7%, n = 77), followed by transthyretin amyloidosis (40%, n = 62) and amyloid A amyloidosis (5.2%, n = 8). Most patients (61.9%, n = 96) presented with multiorgan involvement. Nevertheless, single organ involvement was seen in all types of amyloidosis, most commonly in amyloid A amyloidosis (75%, n = 6). The median observation time of the surviving patients was calculated by the reverse Kaplan-Meier method and was 3.29 years (95% confidence interval [CI] 2.33-4.87); it was 4.87 years (95% CI 3.14-7.22) in light-chain amyloidosis patients and 1.85 years (95% CI 1.48-3.66) in transthyretin amyloidosis patients, respectively. The 1-, 3- and 5-year survival rates were 87.0% (95% CI 79.4-95.3%), 68.5% (95% CI 57.4-81.7%) and 66.0% (95% CI 54.6-79.9%) respectively for light-chain amyloidosis patients and 91.2% (95% CI 83.2-99.8%), 77.0% (95% CI 63.4-93.7%) and 50.6% (95% CI 31.8-80.3%) respectively for transthyretin amyloidosis patients. There was no significant difference between the two groups (p = 0.81). During registry set-up, a more comprehensive work-up of our patients suffering mainly from light-chain amyloidosis and transthyretin amyloidosis was implemented.Survival rates were remarkably high and similar between light-chain amyloidosis and transthyretin amyloidosis, a finding which was noted in similar historic registries of international centres. However, further studies are needed to depict morbidity and mortality as the amyloidosis landscape is changing rapidly.

From variant of uncertain significance to likely pathogenic in two siblings with atypical RAG2 Deficiency: a case report and review of the literature

BackgroundSevere combined immunodeficiencies (SCIDs) are hereditary disorders characterized by impaired T and B cell function, resulting in significant immune system dysfunction. Recombination-activating gene (RAG) mutations account for a substantial proportion of SCID cases. Here, we present two sibling cases of SCID caused by a novel RAG2 gene mutation.Case PresentationThe index case was an 8-year-old boy who had a history of recurring infections. After a comprehensive immunological workup, the initial diagnosis of agammaglobulinemia was revised to combined immunodeficiency (CID). The patient underwent hematopoietic stem cell transplantation (HSCT) but succumbed to cytomegalovirus (CMV) infection. His brother, a 4-month-old boy, presented with CMV chorioretinitis. Leaky SCID was diagnosed based on genetic tests and immunological findings. The patient received appropriate treatment and was considered for HSCT. Both siblings had a homozygous RAG2 gene variant, with the first case classified as a variant of uncertain significance (VUS). The presence of the same mutation in the second brother, and the clinical phenotype, supports considering the mutation as likely pathogenic.ConclusionsThis case report highlights a novel RAG2 gene mutation associated with CID. The classification of a VUS may evolve with accumulating evidence, and additional studies are warranted to establish its pathogenicity. Proper communication between genetic counselors and immunologists, accurate documentation of patient information, increased public awareness, and precise utilization of genetic techniques are essential for optimal patient management.

Variable clinical expression of a novel FLNC truncating variant in a large family

BackgroundVariants in Filamin-C (FLNC) have been associated with various hereditary cardiomyopathies. Recent literature reports a prevalence of sudden cardiac death (SCD) of 13–25% among carriers of truncating-variants, with mean age of 42±15 years for first SCD event. This study reports two familial cases of SCD and the results of cascade screening of their large family. MethodsMolecular-autopsy of the SCD victims revealed a novel truncating-variant in the FLNC gene (chr 7:128496880 [hg19]; NM_001458.5; c.7467_7474del; p.(Ser2490fs)). We screened thirty-two family members following genetic counseling, and variant carriers underwent a comprehensive workup followed by consultation with a cardiologist with expertise in the genetics of cardiac diseases. ResultsSeventeen variant carriers were identified: ages between 9 and 85 (mean 47±26). Fifteen underwent clinical evaluation. To date, none of the identified carriers has had major adverse events. In evaluated patients, ECG showed right-axis deviation in 60% (n = 9). Holter recorded frequent premature ventricular contractions (PVCs) (991±2030 per 24 h) in 33% (n = 5) with 4 patients having polymorphic PVC morphology. Three carriers had echocardiographic evidence of mild left-ventricular (LV) systolic dysfunction and another with mild LV dilatation. Cardiac magnetic-resonance (CMR) exhibited late‑gadolinium-enhancement in 10 out of 11 exams, mainly in the mid-myocardium and sub-epicardium, frequently involving the septum and the inferior-lateral wall. ConclusionThis large FLNC truncating variant carrier family exhibits high cardiomyopathy penetrance, best diagnosed by CMR, with variable clinical expressions. These findings present a challenge in SCD prevention management and underscoring the imperative for better risk stratification measures.

Diagnosis of primary vitreoretinal lymphoma masquerading infectious retinitis by retinal biopsy

PurposeTo report a case of primary vitreoretinal lymphoma masquerading as infectious retinitis that was diagnosed via a retinal biopsy.ObservationsA 72-year-old female patient was referred to our ophthalmology clinic for evaluation of retinitis and vasculitis in the right eye (OD). On examination, best-corrected visual acuities (BCVAs) were hand motions OD and 20/20 in the left eye (OS). Fundus examination revealed optic disc edema and diffuse retinal whitening superior to the superotemporal arcade OD. Given the high suspicion of infectious retinitis, the patient was treated with intravitreal foscarnet, systemic acyclovir, and oral prednisone and underwent a comprehensive uveitis workup, which was unremarkable for viral and autoimmune entities. Given the patient’s history of diffuse large B cell lymphoma with cutaneous involvement, vitreoretinal lymphoma was suspected, prompting pars plana vitrectomy with a retinal biopsy. Biopsy and immunohistochemistry results were consistent with B-cell lymphoma, and the patient was treated with high-dose methotrexate and rituximab. At 5-month follow-up, BCVAs were hand motions OD and 20/30 OS, and fundus examination demonstrated disc edema with resolution of retinal whitening OD. She responded well to the treatment with regression of vitreoretinal lymphoma on examination and is being monitored closely for lymphoma recurrence.Conclusions and importanceAlthough uncommon, patients with vitreoretinal lymphoma may masquerade as infectious retinitis, and vitreoretinal lymphoma should be suspected when refractory to antiviral therapy and in the setting of a negative workup for viral etiologies. Vitrectomy with retinal biopsy may be considered to aid the diagnosis of vitreoretinal lymphoma although careful consideration of the risks and benefits is warranted.

(193) Bilateral Onco-TESE and Placement of Bilateral Testicular Prostheses

Abstract Introduction Here we present the case of a 36-year-old male who underwent bilateral Onco-TESE (oncologic testicular sperm extraction) and insertion of bilateral testicular prostheses in the setting of bilateral testicular masses and refractor testicular pain. Preoperative evaluation revealed the presence of non-obstructive azoospermia and Klinefelter syndrome. Objective To demonstrate the effectiveness and feasibility of bilateral Onco-TESE as a therapeutic option for the patient with bilateral testicular masses, refractory bilateral testicular pain, non-obstructive azoospermia, and Klinefelter syndrome while attempting to preserve future fertility. Methods A comprehensive diagnostic workup was performed preoperatively including physical examination, scrotal ultrasound, hormonal evaluation, semen analysis, and genetic testing. Informed consent for the procedure and its filming was obtained from the patient prior to undergoing bilateral Onco-TESE and insertion of bilateral testicular prostheses. Results Pathologic analysis of testicular masses revealed Multinodular Leydig cell hyperplasia. The extracted testicular tissue yielded no viable sperm. The patient’s testicular pain resolved after the immediate postoperative period with an excellent cosmetic result. Conclusions This case presentation highlights a unique indication for bilateral Onco-TESE and insertion of bilateral testicular prostheses in a patient with bilateral testicular masses, bilateral testicular pain, Klinefelter syndrome, and desired future fertility. Disclosure No.