Progressive Clinical Course Research Articles

Thoracolumbar meningeal fibrosis in pugs.

BackgroundThoracolumbar myelopathies associated with spinal cord and vertebral column lesions, with a similar clinical phenotype, but different underlying etiologies, occur in pugs.ObjectivesTo further characterize the clinical and neuropathological characteristics of pugs with longstanding thoracolumbar myelopathy.AnimalsThirty client‐owned pure‐bred pugs with a history of more than a month of ataxia and paresis of the pelvic limbs, suggesting a myelopathy localized to the thoracolumbar spinal cord, were included in the study.MethodsProspective clinicopathological study. Included pugs underwent a complete neurological examination and gross and histopathologic postmortem studies with focus on the spinal cord. Computed tomography (n = 18), magnetic resonance imaging (n = 17), and cerebrospinal fluid analysis (n = 27) were performed before or immediately after death.ResultsTwenty male and 10 female pugs had a median age at clinical onset of 84 months (interquartile range, 66‐96). Affected pugs presented with a progressive clinical course and 80% were incontinent. There was circumferential meningeal fibrosis with concomitant focal, malacic, destruction of the neuroparenchyma in the thoracolumbar spinal cord in 24/30 pugs. Vertebral lesions accompanied the focal spinal cord lesion, and there was lympho‐histiocytic inflammation associated or not to the parenchymal lesion in 43% of the pugs.Conclusions and Clinical ImportanceMeningeal fibrosis with associated focal spinal cord destruction and neighboring vertebral column lesions were common findings in pugs with long‐standing thoracolumbar myelopathy.

Reed Sternberg-Like Cells in an Aggressive Lymphoma: Report of a Rare Case and Review of Literature

Peripheral T-cell lymphomas are aggressive lymphomas with a rapidly progressive clinical course and sinister prognosis even with the best available treatment modalities. Epstein–Barr virus-positive peripheral T-cell lymphoma is an unusual variant of the disease; it is extremely rare and associated with a fulminant course spanning weeks to months. Treatment protocols are different for this entity because of its rarity.

Cardiac functions and aortic elasticity in children with inflammatory bowel disease: effect of age at disease onset

Childhood onset inflammatory bowel disease is more aggressive and has rapidly progressive clinical course than adult inflammatory bowel disease. Early-onset inflammatory bowel disease has more severe clinical progression as a subspecialised group of monogenic inflammatory bowel disease. We studied cardiac functions and aortic elasticity in children with early- and late-onset inflammatory bowel disease in remission period. Thirty-three paediatric patients were divided into subgroups according to age of disease onset (<10 and >10 years of age). Twenty-five healthy children were admitted as control group. M-Mode echocardiography and pulsed wave Doppler echocardiography were performed. Strain, distensibility, stiffness index of ascending, and abdominal aorta were evaluated. Interventricular septum (mm) and left ventricular end-systolic diameter were higher (6.9 ± 1.2, 26.2 ± 4.6) in early-onset inflammatory bowel disease patients than control patients (6.1 ± 1.27, 22.7 ± 4.12) (p = 0.050, p = 0.050). Mitral E/E' ratio and myocardial performance index were increased in inflammatory bowel disease and early-onset inflammatory bowel disease groups than control group (p = 0.046, p = 0.04; p = 0.023, p = 0.033). Diastolic functions were found to beimpaired in inflammatory bowel disease and early-onset inflammatory bowel disease groups according to control group, while there was no difference between late-onset inflammatory bowel disease and control groups in terms of diastolic functions. Mitral E/A ratio was lower in inflammatory bowel disease patients and early-onset inflammatory bowel disease patients (1.46 ± 0.32, 1.4 ± 0.21) than control patients (1.70 ± 0.27) (p = 0.013, p = 0.004). Aortic elasticity did not differ between groups. Chronic low-grade inflammation has effects on left ventricular diameters and diastolic function in remission period. Aortic elasticity is not affected in our study groups.

Determinants of Disability in Progressive Onset Multiple Sclerosis.

To describe the clinical and socio-demographic profiles of the patients with the progressive onset Multiple Sclerosis (MS) and to explore the determinants of disability. This is a retrospective study, which was conducted in a university hospital. Patients with a progressive clinical course at onset were included in the study. In the first analysis, the clinical and demographic properties of the cohort were defined. In the second analysis the effects of age, sex, clinical activity during course, initial clinical symptoms and cerebrospinal fluid analyses on the course were evaluated. Clinical activity during the course, older age, male gender, medulla spinalis involvement at onset and detection of paraparesis at initial neurological examination was found as a poor prognostic factor. This research confirms previous findings of the studies conducted in populations of Europe and America. Further studies are needed to confirm and validate these findings and to provide greater insight into the effects of ethnic or geographical differences on the course.

Prediction of the Clinical Severity of Progressive Supranuclear Palsy by Diffusion Tensor Imaging.

Progressive supranuclear palsy (PSP) is characterized by a rapid and progressive clinical course. A timely and objective image-based evaluation of disease severity before standard clinical assessments might increase the diagnostic confidence of the neurologist. We sought to investigate whether features from diffusion tensor imaging of the entire brain with a machine learning algorithm, rather than a few pathogenically involved regions, may predict the clinical severity of PSP. Fifty-three patients who met the diagnostic criteria for probable PSP were subjected to diffusion tensor imaging. Of them, 15 underwent follow-up imaging. Clinical severity was assessed by the neurological examinations. Mean diffusivity and fractional anisotropy maps were spatially co-registered, normalized, and parcellated into 246 brain regions from the human Brainnetome atlas. The predictors of clinical severity from a stepwise linear regression model were determined after feature reduction by the least absolute shrinkage and selection operator. Performance estimates were obtained using bootstrapping, cross-validation, and through application of the model in the patients who underwent repeated imaging. The algorithm confidently predicts the clinical severity of PSP at the individual level (adjusted R2: 0.739 and 0.892, p < 0.001). The machine learning algorithm for selection of diffusion tensor imaging-based features is accurate in predicting motor subscale of unified Parkinson’s disease rating scale and postural instability and gait disturbance of PSP.

Viral Pneumonia Requiring Differentiation from Acute and Progressive Diffuse Interstitial Lung Diseases.

Objective The clinical characteristics and chest imaging findings of viral pneumonia and several interstitial lung diseases (ILDs) overlap, and viral pneumonia may be underrecognized and misdiagnosed as certain ILDs. To clarify the frequency of viral pneumonia among patients with acute progressive clinical courses that required a differential diagnosis between ILDs and pneumonia, and to determine the most frequent ILDs misdiagnosed in cases of viral pneumonia. Patients and Methods We retrospectively analyzed patients hospitalized from 2010 to 2017 with an acute clinical course (≤30 days) who underwent bronchoalveolar lavage (BAL) for the differential diagnosis of infection and ILDs. We performed a multiplex PCR for respiratory viruses using the patients' preserved BAL fluid. The final diagnosis was made by a multidisciplinary approach and after considering the PCR results. The diagnosis at discharge was compared to the final diagnosis. Results Among the 109 patients, 53 were diagnosed with viral pneumonia. Viral pneumonia and other diseases showed some differences in symptoms and laboratory data; however, the differences were small or overlapped. Viral pneumonia was misdiagnosed on discharge as acute fibrinous organizing pneumonia, cryptogenic organizing pneumonia, or chronic eosinophilic pneumonia (AFOP/COP/CEP) (n=22), acute interstitial pneumonia (n=5), connective tissue disease-related ILDs (n=3), unclassifiable interstitial pneumonia (n=2), drug-induced ILD (n=1), and pneumonia (n=20). Conclusion Approximately half of the patients who underwent BAL had viral pneumonia. The most common ILD-related misdiagnoses were AFOP/COP/CEP. Differences in symptoms and laboratory findings between viral pneumonia and other diseases were small, and viral pneumonia should be included in the differential diagnosis when physicians encounter cases in which the abovementioned ILDs are suspected.

Association of variability in antibody binding affinity with a clinical course of anti-MAG neuropathy

Anti-myelin-associated glycoprotein (MAG) neuropathy is mediated by the binding of IgM M-proteins to the human natural killer-1 epitope of several glycoconjugates, including MAG and phosphacan. We recently reported that IgM M-proteins with a higher ratio of anti-phosphacan titer to anti-MAG titer (P/M ratio) were associated with a progressive clinical course. Herein, we investigated the temporal variability of the P/M ratio. The results showed that P/M ratios in worsened cases were significantly increased relative to stable or improved cases. Thus, temporal variability in the specificity of IgM M-proteins may be related to the disease course of anti-MAG neuropathy.

Lamotrigine-induced hemophagocytic lymphohistiocytosis with Takotsubo cardiomyopathy: a case report

BackgroundHemophagocytic lymphohistiocytosis is a rare hematological syndrome characterized by excessive and uncontrolled activation of the immune system. The often nonspecific nature of early symptoms and the potential for progression to multiorgan failure and death if appropriate therapy is not started promptly, highlight the importance of heightened recognition for this uncommon disease. Although there are well-described associations of hemophagocytic lymphohistiocytosis with infectious, malignant, and autoimmune diseases and an established treatment protocol for these cases, the link between medications and hemophagocytic lymphohistiocytosis is less clearly established and the optimal treatment of these cases less well defined.Case presentationHere we describe the case of a 45-year-old caucasian woman presenting with signs and symptoms consistent with hemophagocytic lymphohistiocytosis, induced by recent exposure to lamotrigine. She had a rapidly progressive clinical course, complicated by multiorgan failure including stress-induced Takotsubo cardiomyopathy and cardiac arrest. With dexamethasone and etoposide therapy, she made a full and sustained recovery.ConclusionsThis case highlights that medication-induced hemophagocytic lymphohistiocytosis appears to respond similarly to the same dexamethasone and etoposide treatment regimen developed for other non-drug-induced forms of hemophagocytic lymphohistiocytosis. With the continued cessation of the offending agent there has not been need for maintenance therapy and no relapse to date. In addition, given the risk for cardiomyopathy, a clinical complication not classically associated with hemophagocytic lymphohistiocytosis, echocardiogram and telemetry monitoring should be considered in the initial workup of suspected hemophagocytic lymphohistiocytosis.

252P - Uterine sarcomas in Qatar: Clinico-pathological characteristics and treatment outcome

BackgroundUterine sarcomas (US) are a rare, heterogeneous group of malignancies that have rapid progressive clinical course and poor prognosis. We are reporting a retrospective review of clinico-pathological characteristics and outcome of therapy of these tumors in Qatar. MethodsRetrospective records of 37 patients with US treated in Qatar between January 2010 and December 2016 were reviewed. They were stratified according to the age at diagnosis, menopausal status, ethnic group, pathological subtype of the tumor, grade, stage and treatment modalities (single vs combined modalities; surgical procedure, radiotherapy treatment, adjuvant and palliative chemotherapy. Diagnostic and pathology work was done in one facility. Treatment plan was discussed in MDT. The surgical treatment options were TAH with our without BSO. The chemotherapy we used is Docetaxel Gemcitabine in adjuvant setting as well as palliative treatment for metastatic cases. Radiotherapy was conducted via external beam irradiation followed by brachytherapy. Overall survival (OS) was obtained from the date of diagnosis to the date of death. For the patients who were alive, data was censored on the date of last follow up visit. ResultsFor the reviewed 37 patients, the range of age was 23-64 years old with median age 47 years. LMS are representing the most frequent subtype seen in 15 patients (40%), ESS- 10 (28%), RMS 6 (16%), MMMT 2 (4 %) and non-specified 4 (12%). The stage of the disease at time of diagnosis was 1 in 26%, stage II in 48%, stage III in 11% and stage IV 15%. Total 23 patients underwent surgical resection, 12 patients (53%) simple hysterectomy and 11 (47%) TAH+BSO with LN dissection. 13 patients receivedchemotherapy, in 7 cases as adjuvant, in 4 combined with radiotherapy and in 2 cases as palliative. 13 patient received radiotherapy and brachytherapy. Median follow up time was 42 months. Thorough the time 10 patients died, 18 are still alive and 9 have lost follow up. The Kaplan Maier Curve showed median OS 40 months. Survival rate after one year was 79% and after 3 years 58%. ConclusionsIn this pattern of population where the majority of US presented in early stages (74%), 42% will die within the first 3 years which reflect the need for running big phase 3 trials for optimization of the treatment approaches. Legal entity responsible for the studyAshraf Fadlelseid. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Rutin as Neuroprotective Agent: From Bench to Bedside.

Flavonoids are major dietary constituents of plant-based food found ubiquitously in plant kingdom where they are usually present in substantial amounts. Rutin is a flavonol-type polyphenol which consists of the flavonol quercetin and the disaccharide rutinose. Rutin has been reported to exert diverse biological effects such as antitumor and antimicrobial mainly associated to its antioxidant and anti-inflammatory activities. Mental, neurological, and behavioural disorders are an important and growing cause of morbidity. Most of these disorders combine a high prevalence, early onset, progressive clinical course, and impairment of critical brain functions making them a major contributor to the global disease burden. In the present work, the biological in vitro and in vivo effects and the potential therapeutic applications of rutin in neurodegenerative processes are reviewed, as well as their bioavailability and pharmacokinetics, which are essential for a better understanding of its biological effectiveness. Moreover, the present review also provides an overview of the molecular mechanisms through which rutin is proposed to exert its neuroprotective effects.

TWO TO TANGO: A MEDLEY OF HYPERSENSITIVITY PNEUMONITIS AND IDIOPATHIC PULMONARY FIBROSIS

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Interstitial Lung Disease (ILD) is a broad group of heterogeneous disorders that share certain pathologic features. Categorization of ILD always necessitates a thorough history, but diagnosis also relies on serologic testing, high-resolution CT, and sometimes bronchoalveolar lavage. When etiology of disease remains unclear, lung biopsy can provide clarity. CASE PRESENTATION: An 81-year-old male presented to the ED with one-year history of dyspnea and productive cough. He had history of large B-cell lymphoma treated with chemotherapy in remission and persistent atrial fibrillation status post cardioversion and intermittent amiodarone use in the last year. The patient noted a steady decline in functional status over several months, but reported to the ED after noting an oxygen saturation at home of 75%. He denied fevers, chills, night sweats, but did endorse recent weight loss. He denied use of tobacco, alcohol, drugs, or recent travel. He denied pet, dander, smoke, asbestos, or other trigger exposure. Vital signs were normal except for an oxygen requirement of 3.5 liters by nasal canula. Exam revealed bibasilar rales on inspiration sans wheeze in an elderly Caucasian male appearing younger than stated age. No abnormalities noted on CBC. Patient had prior RF > 1000 and ANA 1:640 but repeat testing included negative ANA, anti-CCP, scleroderma, myeloperoxidase, anti-SSA, anti-SSB, and anti-Smith antibodies. Echocardiogram was unremarkable. Chest CT showed multifocal pulmonary opacities and septal thickening, reticular opacities in lower lungs, and enlarged mediastinal lymph nodes, likely reactive. PFTs showed a mild restriction pattern with a diffusion capacity 41% of predicted. Hypersensitivity panel was unremarkable. Lung biopsy showed hypersensitivity pneumonia with usual interstitial pneumonia (UIP)-like fibrosis. Discussion across specialists yielded a diagnosis of acute hypersensitivity pneumonitis secondary to amiodarone toxicity with underlying fibrosis which may represent Idiopathic pulmonary fibrosis (IPF). DISCUSSION: While this patient's initial presentation was concerning for a rheumatologic-associated ILD from non-specific interstitial pneumonia, repeat serology and pathology led to amiodarone-induced hypersensitivity pneumonitis. This case is unique because pathology revealed well-formed granulomas in the peribronchiolar interstitium with a background of UIP-like fibrosis. These findings led to a conclusion of a primary acute hypersensitivity pneumonitis superimposed upon more chronic fibrosis. While this patient is currently responding well to steroids, long-term he is likely to experience a progressive clinical course typical of IPF patients. CONCLUSIONS: Classifying interstitial lung diseases is challenging and relies on detailed history, serologies, imaging, and often pathology. Multispecialty input should be pursued to obtain the most accurate diagnosis and treatment plan. Reference #1: Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 2008; 63 Suppl 5:v1. Reference #2: Pipavath S, Godwin JD. Imaging of interstitial lung disease. Clin Chest Med 2004; 25:455. DISCLOSURES: No relevant relationships by Katherine Axon, source=Web Response No relevant relationships by Allison Palmer, source=Web Response No relevant relationships by Siva Parcha, source=Web Response No relevant relationships by Adam Smalley, source=Web Response

COXSACKIE B2 VIRUS: FROM A SOCCER GAME TO FULMINANT MYOCARDITIS

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: The presentation of viral myocarditis ranges from no symptoms to devastating illness.1 This is an unfortunate case of Coxsackie B2 virus induced Fulminant Myocarditis (FM); which despite aggressive medical and mechanical circulatory support progressed to fatality. CASE PRESENTATION: A 20-year-old male patient was transferred to our hospital with respiratory failure and shock. He presented to his local hospital with dyspnea, fever, myalgias and arthralgias that started after an indoor soccer game two weeks earlier. Prior to admission he was treated with inhalers, steroids and antibiotics without improvement. The TTE showed an LVEF 30% and Chest CT Scan showed bilateral consolidations and multiple nodules surrounded by ground glass opacities. Mechanical ventilation, vasopressors and inotropes were initiated prior to transferring him to our hospital. Upon arrival he required paralysis and pronation to improve his hypoxia. He was started on broad spectrum antimicrobials. However, the initial infectious workup was negative. Further workup obtained due to persistent fever revealed portal vein thrombosis which was treated with heparin. Hypercoagulability, malignancy and rheumatology tests were unrevealing. Expanded infectious workup was most notable for positive Coxsackie B2 serology with titers that increased 4-fold during hospitalization to 1:320, consistent with viral myocarditis. TEE showed persistent LV dysfunction, global LV wall motion abnormalities, increased septal wall thickness, severe mitral regurgitation and moderate tricuspid regurgitation. After receiving diuretics, vasopressors and inotropes he improved and was extubated. He subsequently decompensated requiring reintubation and resumption of inotropes. ECMO was initiated with biventricular assist device support. Heart transplant was considered but his hospital course was complicated by severe deconditioning and went on to develop GI bleeds, acute renal failure, fungemia, pulmonary abscess status post decortication and contained pulmonary artery rupture. On ICU day #97, his illness was deemed not survivable and his family withdrew care. DISCUSSION: Coxsackie B serotypes are among the more common causes of viral myocarditis, which may evolve into FM.2 FM is defined as 2-4 weeks of acute illness, followed by cardiogenic shock, needing hemodynamic support; and myocardial inflammatory infiltrates on histology. FM has a dramatic and progressive clinical course, with a severely impaired LVEF.3 It often requires prolonged hemodynamic support and referral for heart transplant.4 In general, in-hospital outcomes are poor; with increased morbidity and up to 32% reported mortality.5 CONCLUSIONS: Coxsackie B induced Fulminant Myocarditis portends increased morbidity and mortality, even after aggressive medical and mechanical circulatory support. Reference #1: Kindermann et al. J Am Coll Cardiol. 2012;59:779–92. Reference #2: Mehta et al. Case Reports in Infectious Diseases. 2018;ID 4258296:1-4. Reference #3: Ammirati et al. Circulation. 2017;136:529-45. DISCLOSURES: No relevant relationships by Stefanie DiGiandomenico, source=Web Response No relevant relationships by Tirsa Ferrer Marrero, source=Web Response No relevant relationships by Javeria Haque, source=Web Response No relevant relationships by Christopher Roberts, source=Web Response No relevant relationships by Gabriel Ryan, source=Web Response no disclosure on file for Jonathon Truwit; No relevant relationships by Krista Tuomela, source=Web Response No relevant relationships by Jane Wainaina, source=Web Response

P1775Outcomes in patients with left ventricular non-compaction phenotype and normal left ventricular ejection fraction

Abstract Introduction Left ventricular non-compaction (LVNC) is a rare cardiomyopathy with a progressive clinical course, resulting in symptoms such as heart failure, cardiac arrhythmias, or thrombo-embolic events. Little is known about the natural course of disease, in particular in individuals with normal LV ejection fraction (EF) at diagnosis. In this study, we aim to evaluate the outcome of this group of patients. Methods 48 LVNC patients with normal LV EF at diagnosis (defined as ≥50% by Simpson) were retrospectively analysed followed-up for median duration of 3656 days (2017–4965). All outcome data and conventional echocardiographic parameters were obtained; and in 27 patients, LV and right ventricular (RV) global longitudinal strain (GLS) were also determined using TomTec Image Arena (v.4.6). Results Mean age was 25.5 years. Median LVEF was 58.5% [IQR: 52.75 - 65.25]). The localization of non-compacted segments displayed a typical distribution with apical and inferolateral midventricular segments most frequently involved. Although LVEF was normal at baseline, median LV GLS was 16.8% (IQR: 20.0 - 14.2) and RV GLS was 18.7% (23.3–15.6). Furthermore, only 30 patients (73.2%) had a normal diastolic function, while others showed impaired relaxation (19.5%; n=8) or restrictive filling pattern (7.3%; n=3). During follow-up, LVEF decreased slightly from the initial visit (59%, [53.3–65.0]) to last follow-up (56%, [53.0–61.8], p=0.0009), and LV end-systolic and end-diastolic volumes increased (p=0.009 and 0.001, respectively). The other echocardiographic parameters did not show any significant changes. During follow-up, 3 patients (7.7%) died, 5 (12.8%) were hospitalized for heart failure, 3 (7.7%) had a thromboembolic event, 5 (12.8%) a syncope, 3 (8.1%) a non-sustained ventricular tachycardia, 9 (22.5%) a supraventricular tachycardia, and 14 (35.9%) suffered other complications during follow-up. The change in LVEF and LV volumes during follow-up was not significantly associated with outcome. Conclusion Patients presenting with a LVNC phenotype and normal LVEF did not display a completely normal LV function as revealed by LV strain and LV diastolic function. LVEF decreased slightly during follow-up, but was surprisingly stable in most patients. Nevertheless, a significant number of individuals experienced a clinically relevant event. Hence, a LVNC phenotype is important even in individuals with normal LVEF and such patients should be followed-up regularly.

E-POSTERS – EARLY ONSET MUSCLE DISEASE – CASE REPORTS: EP.120ADSSL1 distal myopathy presenting with a more rapid progressive course in patient with trisomy 21

We report a 22 year old female of mixed European and Mexican background with novel compound heterozygous ADSSL1 gene mutations (p.Gly326Asp, pat and c.1202+1G>A, mat) identified by exome sequencing with a more progressive clinical course due to her other diagnosis of trisomy 21 (T21). Her development was appropriate for T21, but she never learned to run, jump or use stairs independently. At age 8 yr, her motor skills started to regress with emergence of weakness. She used a walker by 10 yr and lost ambulation at 12 yr. Currently, she cannot weight-bear (strength 1/5 in most leg muscles; quadriceps at 1-2/5), but has more preserved upper extremity use (strength 3 to 3-/5 range). She has hip, knee contractures, end-grade elbow contractures, and coexistence of finger flexor contractures with laxity in PIP and DIP joints. Her cognitive delays are typical for T21. She developed progressive scoliosis that required T4-L4 spinal fusion at 12 yr of age. There is no cardiomyopathy and her LVSF is 36%. Nocturnal hypoventilation started at age 13 yr with use of BiPAP during sleep since 16 yr of age. Unlike previously reported cases, she had a normal CK and her muscle biopsy at 14 yr did not show rimmed vacuoles or nemaline rods but rather severe myopathic changes: fibrosis and adipose infiltration, variation in fiber size with small, atrophic fibers intermixed with hypertrophic fibers, rounded and splitting fibers, increased central nuclei and occasional degenerating/regenerating fibers. To date, ADSSL1 gene mutations, encoding an enzyme converting inosine monophosphate (IMP) to adenosine monophosphate (AMP), have been reported only in 9 Korean patients from 6 families with 8 of the 9 patients having the same compound heterozygous mutations, suggesting a founder-effect. Identification of another patient with novel mutations suggests that this form of myopathy is panethnic and likely underdiagnosed among patients presenting with signs of generalized and distal myopathy.

Clinical course of patients with pantothenate kinase-associated neurodegeneration (PKAN) before and after DBS surgery.

Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive disorder with a progressive clinical course. In addition to symptomatic therapy, DBS has been increasingly recognized as a potential therapeutic strategy, especially in severe cases. Therefore, we wanted to report our experience regarding benefits of DBS in five PKAN cases in 3-year follow-up study. Five genetically confirmed PKAN patients from Serbia underwent GPi-DBS. To assess clinical outcome, we reviewed medical charts and applied: Schwab and England Activities of Daily Living Scale (S&E), EQ-5D questionnaire for quality of life, Patient Global Impression of Improvement (GPI-I), Functional Independence Measure (FIM), Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Barry Albright Dystonia Scale (BAD). Patients were evaluated in five visits: at the disease onset, 5years after the onset, before surgery, 6months and 14-36months after the surgery. Improvement of 20% was accepted as significant. Overall, dystonia significantly improved after GPi-DBS at 6 and 14-36months postoperatively, when assessed by the BFMDRS and BAD. However, two patients failed to improve considerably. Four patients reported improvement on GPI-I, while one remained unchanged. Three patients reported significant improvement, when assessed with S&E and FIM. EQ-5D showed the most prominent improvement in the domains of mobility and pain/discomfort. Three out of our five patients experienced beneficial effects of the GPi-DBS, in up to 36months follow-up. Two patients who had not reached significant improvement had longer disease duration; therefore, it might be reasonable to recommend GPi-DBS as soon as dystonia became disabling.

Patient hand and artistic depiction of chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired inflammatory demyelinating disease affecting nerve roots and peripheral nerves with a monophasic, progressive, or relapsing clinical course, often with incomplete recovery potentially leading to lifelong disability.1,2 As physicians it is important to remember the effect of CIDP on afflicted patients reaches beyond what can be examined or observed, with persisting alterations in body image from chronic denervation, sensory deafferentation, and weakness contributing to less measurable disability. This patient's creative interpretation of the long-term sequela of this disorder reflects how she perceives her chronic disability and embodies her perseverance through art (figures 1 and 2).

Significance of IL-17A-producing CD8+CD103+ skin resident memory T cells in psoriasis lesion and their possible relationship to clinical course

BackgroundA number of studies have shown the relationship between the pathogenesis of psoriasis and skin resident memory T (TRM) cells. ObjectiveTo investigate the cytokine profile of TRM cells from skin lesions of psoriasis and the relationship of skin TRM cells to the future clinical course of psoriasis. MethodsWe used stocked samples of T cells that were ex vivo expanded from skin biopsies of 10 patients with psoriasis vulgaris. A half of 4-mm punch biopsy specimens was subjected to expansion of skin-infiltrating T cells using IL-2 and anti-CD3/CD28 antibody-coated microbeads. More than 106 T cells per specimen were stocked at −80°C. Defrosted cells were subjected to flow cytometric analysis. Another half of skin biopsies were subjected to immmunofluorescence staining for CD103 and other markers. ResultsThe biopsied skin revealed CD8+CD103+ TRM cells were present in the epidermis of psoriasis and associated with acanthosis. Sorted CD103+ T cells were mostly CD8+ memory T cells expressing CD69 with a skin-homing potential. A part of CD8+CD103+ T cells produced interferon-γ, IL-17A or IL-22. Notably, CD8+CD103+ TRM cells more frequently produced IL-17A than did CD8+CD103− T cells. We retrospectively divided the 10 cases into the non-advanced therapy group, and the advanced therapy group in which systemic biologics or others were initiated within one year. The frequency of CD8+CD103+IL-17A+ TRM cells tended to be higher in the advanced therapy group. ConclusionThese results suggest that IL-17A-producing CD8+CD103+ TRM cells are associated with a progressive clinical course of psoriasis.

Necrotiserende eosinofiele dermatitis bij drie honden

In dit artikel wordt bij drie honden necrotiserende eosinofiele dermatitis beschreven met een acuut ontstaan en snel verloop. De eerste huidletsels werden gekenmerkt door intens jeukende erythemateuze en stevig aanvoelende intacte papels en plaques. De letsels werden snel groter en evolueerden tot samenvloeiende targetoïde nodulen met centrale exsudatie, ulceratie en necrose. De letsels kwamen hoofdzakelijk voor op de hals en op de dorsolaterale romp. Eén hond vertoonde ook orale letsels. Het histopathologisch beeld toonde in de drie gevallen eosinofiele dermatitis en panniculitis gericht op de dermale en subcutane bloedvaten met secundaire aantasting van de haarfollikels. Een overgevoeligheidsreactie op medicatie of op andere lichaamsvreemde antigenen kunnen mogelijk de oorzaak zijn geweest.

The impact of cervical spinal cord atrophy on quality of life in multiple sclerosis

BackgroundSpinal cord demyelination is common in multiple sclerosis (MS) and has been linked to increased disability and progressive clinical course. Spinal cord atrophy shows an especially close relationship to MS-related physical disability, though the relationship between spinal cord lesions/atrophy and health-related quality of life (QOL) has not been explored. Methods62 patients (53 relapsing MS, 7 secondary progressive, 2 clinically isolated syndrome) from our center underwent 3 T MRI within 30 days of clinical examination and QOL assessment. Upper cervical (C1-C3) spinal cord area (UCCA) was obtained from 3D high-resolution MPRAGE sequences (1 mm isotropic voxels). Cervical spinal cord (C1-C7) lesion count, and cervical and brain T2 hyperintense lesion volumes were calculated. Brain parenchymal fraction (BPF) was obtained from an automated segmentation pipeline. Spearman correlations were assessed between MRI and clinical data. Partial Spearman correlations adjusting for age, disease duration, and BPF assessed the independent association between MRI variables and QOL domains. ResultsUCCA showed an inverse relationship with age (r = −0.330, p = .009), disease duration, (r = −0.444, p < .001), and nine-hole peg test (r = −0.353, p = .005). The Upper Extremity Function QOL domain showed the strongest relationship to UCCA (r = 0.333, p = .008), with Lower Extremity Function QOL (r = 0.234, p = .067) and Satisfaction with Social Roles and Activities (r = 0.245, p = .055) correlations bordering significance. The association between UCCA and Upper Extremity QOL remained significant after adjustment for BPF, age, and disease duration. QOL domains reflective of psychological health (Depression, Anxiety, Emotional and Behavioral Dyscontrol, Positive Affect and Wellbeing) showed no relationship to UCCA. Cervical and brain lesion volume related to impairment in Stigma while cervical lesion count was unrelated to NeuroQOL impairment. Brain atrophy correlated with conventional markers of disability and cognition but did not have a significant relationship to QOL. ConclusionCervical spinal cord volume is independently associated with impaired upper extremity-related QOL in patients with MS. These findings suggest specific clinical relevance of MS-related spinal cord atrophy as compared to brain or cervical spinal cord lesions, or whole brain atrophy.

Lymphomatoid Granulomatosis: Rare Radiologic Presentation as a Solitary Pulmonary Mass

Background: Lymphomatoid granulomatosis (LYG) is a rare Epstein-Barr virus (EBV)-driven lymphoproliferative disease. LYG is characterized by a progressive clinical course, which virtually always involves the lungs. LYG characteristically presents as bilateral pulmonary nodules. Pathologically, it is characterized by an angiocentric and angiodestructive infiltration of atypical EBV-positive B-lymphocytes admixed with reactive T-lymphocytes. We report a case of pulmonary LYG that presented as a large mass with complete occlusion of the right main stem bronchus intermedius in an 81-year-old female. Case: An 81-year-old female presented with shortness of breath to the emergency department. Inpatient imaging revealed bulky mediastinal lymphadenopathy with a right lower lobe collapse, shift of the cardiomediastinal silhouette, and a large right upper lung mass. Endobronchial ultrasound-guided biopsy (EBUS) revealed complete occlusion of right mainstem bronchus due to the right upper lung mass growth into the bronchus intermedius. Histopathological examination demonstrated clusters of large atypical EBV-positive B cells interspersed in a minimally polymorphous lymphocytic background, consistent with lymphomatoid granulomatosis, grade 3/3. Patient was treated with immunochemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone - CHOP) and Rituximab (anti-CD20 antibody). At the patient’s most recent follow-up, 6 months later, she was in a stable condition and her respiratory symptoms have improved. Conclusion: Lymphomatoid granulomatosis is a rare disease that should be considered in the differential diagnosis of a radiographic evaluation of a solitary pulmonary lung mass. Since the radiographic impression might favor carcinoma as the top differential diagnosis, biopsy of the lesion is paramount to ensure the correct diagnosis. Lymphomatoid granulomatosis is usually treated with an immunochemotherapy regimen with CHOP, and/or interferon, and Rituximab.