Positive Inflammatory Markers Research Articles

P166 Assessing the effectiveness of a musculoskeletal rheumatology back pain questionnaire in early referral and diagnosis of ankylosing spondylitis in uveitis patients

Abstract Background/Aims Spondyloarthritis represents a chronic inflammatory condition primarily targeting the joints of the spine. Uveitis stands as the most common initial extra-articular manifestation of axial spondyloarthritis (SpA), occurring in up to a third of patients. There is a diagnostic delay in axial SpA, with studies showing that the time from symptom onset to diagnosis is 5-7 years. The delay of diagnosis can be attributed to the non-specific presentation of chronic back pain as well as late ophthalmology referrals to rheumatology. A previous audit in our department showed that 25% of uveitis patients who were clinically indicated to have been referred to rheumatology were not. One main objective was to implement the use of the MSK Rheumatology Inflammatory Back Pain Questionnaire as a referral tool, to find out whether the relevant history and questions were asked to all uveitis patients, to mitigate diagnostic delays and enable early management. Methods Patients presenting to the uveitis clinic at NGH were reviewed prospectively from May 2023-July 2023. Medi-viewer/Symphony were used to see patient details, whether the patients were already under rheumatology, any previous episodes and family history. The MSK Rheumatology Inflammatory Back Pain questionnaire was completed by all attending patients. It included 12 questions; a score ⩾4 signified a need for referral. Results A total of 40 patients (M:F ratio 2:3, mean age 52) presented to the uveitis clinic and were reviewed. All patients with uveitis were investigated with the relevant blood tests to rule out any inflammatory conditions. 16 patients were HLA B27 positive. All patients were asked to complete MSK Rheumatology Inflammatory Back Pain questionnaires to rule out inflammatory disease. 60% had back pain history before the age of 45, 21 were of inflammatory type of pain, 15 had disturbed second half of sleep. 25% of patients had other positive inflammatory markers. 40% of patients had a strong family history of HLA-B27. 67% scored ⩾4 on our questionnaire. 23% were already under rheumatology care, 20% were referred to rheumatology and 23 were not referred, of which 13/23 scored ⩽4. The remaining 10 were not referred due to awaiting blood results, further follow up, or lack of systemic features resulting in discharge. Conclusion Uveitis ranks among the most frequent occurrences in the field of ophthalmology, with a significant proportion being associated with HLA-B27. A considerable 40% of uveitis patients have undiagnosed spondyloarthritis due to inadequate referrals. A comprehensive questionnaire and utilising pain scoring can serve as effective tools for directing patients toward proper evaluation for inflammatory diseases. Our study shows that only appropriate cases were referred and had relevant investigations before referral, underscoring the importance of a partnership between ophthalmology and rheumatology to optimise the management of inflammatory spondyloarthritis. Disclosure F. Bangash: None. N. Kalla: None. A. Bangash: None. A. Rahim: None. M. Kamal: None. I. Mahmood: None.

Clinico-endoscopic and biochemical parallels of chronic inflammatory bowel diseases with positive inflammatory markers

Background. The prevalence of inflammatory bowel disease (IBD) is currently increasing worldwide and represents a serious problem that causes interest in the study and, especially, in the development of less invasive diagnostic measures. In the studies of years on the diagnosis of IBD, there are data indicating the possibility of using IgG4 as a diagnostic biomarker. Purpose: to investigate the peculiarities of endoscopic manifestations and activity of IBD depending on the disease severity, the levels of fecal calprotectin (FC) and IgG4. Materials and methods. One hundred patients with IBD were examined, including 75 people with ulcerative colitis (UC) and 25 with Crohn’s disease (CD). Patients were divided into groups depending on the nosology and severity of the course. All of them underwent an endoscopic examination to verify the diagnosis; the level of IgG, IgG4 in blood serum, the IgG4/IgG ratio, and the content of FC were determined. Results. A significant increase in the degree of endoscopic activity was detected along with an increase in the severity of ulcerative colitis and Crohn’s disease. It was found that the level of FC increased with increasing severity of UC and CD. In patients with UC and CD, a probable decrease in the level of IgG was revealed (p<0.05). The concentration of IgG4 in the group of patients with UC was 2.3 (p<0.05) and 2.5 times (p<0.05) higher compared to the control group and patients with CD, respectively. A correlation was found between the level of IgG4 and the index of Best, the degree of severity, the localization of the inflammatory process in the colon, and the ratio of IgG4/IgG. The relationship of the IgG4/IgG ratio with the endoscopic index of IBD activity and serum IgG4 was revealed. Conclusions. The degree of endoscopic activity of IBD increased along with the severity of the disease. A positive correlation was found between the FC level and the severity of IBD and an inverse correlation— with IgG level. The level of IgG4 depended on the endoscopic activity of IBD, which was confirmed by a correlation. A 2-fold (p<0.05) and 2.5-fold (p<0.05) increase was found in the concentration of IgG4 in the blood serum of patients with UC compared to the control group and patients with CD, respectively. The obtained data can be used for differential diagnosis of UC and CD.

Neonatal multisystem inflammatory syndrome associated with prenatal maternal SARS-CoV-2 exposure: a case series

Multisystem inflammatory syndrome (MIS-C) in children (MIS-C) associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) is well recognised in children, however, rarely reported in newborns. It usually presents as fever and multiorgan involvement, with blood investigations showing increased inflammatory markers weeks after exposure to SARS-CoV-2. Unlike older children, the mechanism is unique in neonates as COVID-19 infection and the subsequent inflammatory reaction leading to MIS-C occur in two different individuals. We reviewed the perinatal history, clinical features, and outcomes of 3 neonates with features consistent with MIS-N related to maternal SARS-CoV-2, from August 2021 to December 2021. Anti-SARS-CoV-2 IgG and IgM antibodies were tested in all neonates. Clinical picture comprised multiorgan dysfunction (gastrointestinal, cardiorespiratory, haematological and dermatological), positive inflammatory markers, high ferritin and high D-dimer levels, elevated Cardiac enzymes. Blood cultures were sterile. Positive anti-SARS-CoV-2 IgG in both the mother and the infant, along with epidemiological evidence of maternal contact with COVID-19, clinched the diagnosis of MIS-C. Immunomodulatory drugs (intravenous immunoglobulin and systemic steroids) were administered. Multisystem inflammatory syndrome should be considered as a differential diagnosis in all critically ill neonates, particularly with maternal history of COVID-19 infection or epidemiological contact. This neonatal presentation is the reflection of fetal inflammatory response syndrome associated with maternal SARS-CoV-2 infection. Having no fever throughout the course of illness, in some neonates, suggests that neonates respond differently compared with children.

Cerebral microbleeds in a young patient – case presentation with rare disease association and literature review

Abstract During the coronavirus pandemic neurology departments were forced to treat diseases that had hitherto been treated by other specialities. In our case presentation, we describe an unusual association of two diseases that raised interesting questions regarding differential diagnostics and has not yet been presented in the literature. A 34-year-old male patient was admitted to the neurology department with an urgent referral because of impaired speech comprehension and expression upon awakening. He had a history of anticoagulant therapy for thrombosis of the posterior tibial artery, discontinued after two weeks. Physical examination revealed a 1 cm diameter painful lump in the subcutis of his right thigh and a systolic murmur over the mitral and aortic valves. Nonenhanced head CT showed a small hemorrhage near the occipital horn of the left ventricle, which could not explain the mixed aphasia. In addition, the SWAN MRI sequence showed supra- and infratentorial microbleeds, suggesting cavernomatosis, which was confirmed by the detection of another typical popcorn-like bleeding cavernoma on repeated MRI examination. Due to the heart murmurs and positive inflammatory markers, a detailed cardiac examination was warranted, confirming infective endocarditis caused by Streptococcus gordonii. Due to COVID-19-related regulations the patient couldn’t be transferred to the Department of Cardiology or Infectious Diseases, thus his treatment and follow-up was carried out at the Department of Neurology. Following targeted antibiotic treatment the patient’s symptoms resolved and he underwent successful cardiac surgery 7 weeks after his discharge in a symptom-free state. The peculiarity of the case lies in the fact that the clinical picture and course of the disease, consistent with the diagnosis of infective endocarditis suggested cerebral septic emboli with microbleeds, but cerebral cavernomatosis was confirmed by brain imaging.

Intraoperative ketorolac in high-risk breast cancer patients. A prospective, randomized, placebo-controlled clinical trial.

BackgroundKetorolac has been associated with a lower risk of recurrence in retrospective studies, especially in patients with positive inflammatory markers. It is still unknown whether a single dose of pre-incisional ketorolac can prolong recurrence-free survival.MethodsThe KBC trial is a multicenter, placebo-controlled, randomized phase III trial in high-risk breast cancer patients powered for 33% reduction in recurrence rate (from 60 to 40%). Patients received one dose of ketorolac tromethamine or a placebo before surgery. Eligible patients were breast cancer patients, planned for curative surgery, and with a Neutrophil-to-Lymphocyte Ratio≥4, node-positive disease or a triple-negative phenotype. The primary endpoint was Disease-Free Survival (DFS) at two years. Secondary endpoints included safety, pain assessment and overall survival.FindingsBetween February 2013 and July 2015, 203 patients were assigned to ketorolac (n = 96) or placebo (n = 107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD14) years.At two years, 83.1% of the patients were alive and disease free in the ketorolac vs. 89.7% in the placebo arm (HR: 1.23; 95%CI: 0.65–2.31) and, respectively, 96.8% vs. 98.1% were alive (HR: 1.09; 95%CI: 0.34–3.51).ConclusionsA single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival difference between ketorolac tromethamine group and placebo group was not statistically significant. The study was however underpowered because of lower recurrence rates than initially anticipated. No safety concerns were observed.Trial registrationClinicalTrials.gov NCT01806259.

Fantom tumor pluća kod pacijenata sa pneumonijom

Introduction: Localized interlobar effusions in congestive heart failure (phantom or vanishing lung tumor/s) are infrequent, but widely recognized entities. Case report: A 80-years-old woman affected by progressive dyspnea over the previous three months, with productive cough. She was treated hypertension and had a pace maker implanted due to bradycardia. Chest X ray has shown right side pneumonia with high positive inflammatory markers. After resolution of pneumonia, phantom tumor of the lung was revealed, which disappear with intensive loop diuretics. Conclusions: The diagnosis of the phantom tumor ought to be pondered as a possibility in any patient with congestive heart failure and lung mass. The patient at hand featured no prior history of congestive heart failure, hence indicating that phantom tumor may occur in non-chronic heart failure patients. Albeid the reliable diagnosis of the phantom tumor through the utilization of imaging modalities in patients without congestive heart failure can be rather challenging, such possibility must be considered in a patient with a lung mass in the major fissure of the lungs. Due to accelerated expansion of the geriatric population and subsequent spread of the congestive heart failure, a rise in the incidence of vanishing tumors of the lung may be anticipated.

EP25.12: Abdominopelvic actinomycosis associated with an intrauterine device: a case report

Actinomycosis is a rare chronic granulomatous suppurative infection caused by an anerobic Gram-positive bacterium, Actinomyces Israelii. Its capacity to invade surrounding tissues and to form masses might mimic other diseases. A 44-year-old woman with an intrauterine device placed 6 years ago, presents with one month history of lower abdominal pain, dyspareunia and fever. Her past medical history was unremarkable, and she had no history of previous abdominal or pelvic surgeries. Physical examination demonstrated generalised abdominal tenderness but no rigidity or guarding. Pelvic examination revealed a tender, solid, fixed pelvic mass, and no vaginal discharge. The patient was febrile. Laboratory investigations demonstrated leucocytosis, positive inflammatory markers and anemia. Transvaginal ultrasound revealed two irregular, heterogeneous, no vascularised, solid masses, one of 70x38x63 mm and other of 62x46x33mm adhered to the posterior uterine wall with apparently normal ovarian parenchyma. Thickening of the sigmoid colonic was also found and posteriorly confirmed by a CT scan, which additionally reported a bilateral hydronephrosis and left paraaortic lymphadenopathy. The main differential diagnoses proposed for the patient were and abdominopelvic actinomycosis or advanced ovarian cancer. The patient underwent laparoscopic surgery. Intraoperative findings confirmed the radiographic diagnosis. Histological results suggested actinomycosis infectious, and no evidence of malignant process. It was performed a partial right adnexectomy and an internal double-J ureteral stents was placed. Subsequently, the patient was treated with intravenous (IV) antibiotic for 6 weeks presenting notorious improvement and was advised to continue gynecological and urological clinical follow up.

Dexamethasone, Intravenous Immunoglobulin, and Rituximab Combination Immunotherapy for Pediatric Opsoclonus-Myoclonus Syndrome

BackgroundAlthough pulse-dose dexamethasone is increasingly favored for treating pediatric opsoclonus-myoclonus syndrome (OMS), and multimodal immunotherapy is associated with improved clinical response, there have been no neuroimmunologic studies of dexamethasone-based multimodal disease-modifying therapy. MethodsIn this observational retrospective study, 19 children with OMS (with or without associated neuroblastoma) underwent multibiomarker evaluation for neuroinflammation. Nine children of varying OMS severity, duration, and treatment status were treated empirically with pulse dexamethasone, intravenous immunoglobulin (IVIg), and rituximab combination immunotherapy (DEXIR-CI). Another 10 children on dexamethasone alone or with IVIg at initial evaluation only provided a comparison group. Motor severity (total score) was scored rater-blinded via videotapes using the validated OMS Evaluation Scale. ResultsDEXIR-CI was associated with a 69% reduction in group total score (P = 0.004) and was clinically well tolerated. Patients given the dexamethasone combination exhibited significantly lowered B cell frequencies in cerebrospinal fluid (−94%) and blood (−76%), normalizing the cerebrospinal fluid B cell percentage. The number of patients with positive inflammatory markers dropped 87% (P = 0.002) as did the number of markers. Cerebrospinal fluid oligoclonal bands were positive in four of nine pretreatment patients but zero of six post-treatment patients. In the comparison group, partial response to dexamethasone alone or with IVIg was associated with multiple positive markers for neuroinflammation despite an average of seven months of treatment. ConclusionsMultimechanistic dexamethasone-based combination immunotherapy increases the therapeutic armamentarium for OMS, providing a viable option for less severely affected individuals. Partial response to dexamethasone with or without IVIg is indicative of ongoing neuroinflammation and should be treated promptly and accordingly.

Non-Complicated Acute Appendicitis in Adults Treated Successfully by Conservative Treatment without Recurrences

AA = Acute Appendicitis, un-AA = Uncomplicated AA, cAA = Complicated Acute Appendicitis, WBC = White Blood Cells, CRP = C-Reactive Protein, U/S = Ultrasound, CT = Computed Tomography, MRI = Magnetic Resonance Imaging, pts = Patients, NET = Neuroendocrine Tumor.

Admission leukocytosis, C-reactive protein and erythrocyte sedimentation rate in acute noncardioembolic cerebral ischemia: influence on early outcome

Background There is growing evidence regarding the role of inflammation in the pathogenesis of ischemic stroke, especially nonembolic types of ischemic stroke. Despite this, there is a need to investigate the direct impact of inflammatory markers on the early outcome in nonembolic ischemic stroke. Objective The aim of the present study was to determine whether positive inflammatory markers such as raised erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and leukocytosis could be used as biochemical predictors for poor early outcome in patients with acute noncardioembolic ischemic stroke. Patients and methods A total of 60 patients(40 men and 20 women; median age: 64.5 years) with first attack of noncardioembolic ischemic stroke were included in the study. Full clinical assessment and routine laboratory investigation were conducted for all patients. MRI of brain, ECG, and cardiac echo were carried out to confirm the diagnosis and exclude cases with embolic stroke. Blood samples for all patients within the first 24 h of onset of symptoms were taken for assessment of ESR, qualitative CRP, and leukocyte count on admission. National Institute of Health Stroke Scale was used for all patients after 7 days. On the basis of their scores patients were divided into two groups: 40 patients with favorable outcome were included in the first group and 20 patients with bad outcome in the second group. Results There was significant difference between the two groups regarding ESR value, and the leukocyte count was higher in the group with bad prognosis. In addition, positive CRP was associated more with the same group in statistically significant way. Conclusion Inflammatory markers play an important role in detecting the early outcome of noncardioembolic stroke.

Small bowel capsule endoscopy in the management of established Crohn's disease: clinical impact, safety, and correlation with inflammatory biomarkers.

Multiple studies have established the superior diagnostic accuracy of video capsule endoscopy (VCE) for the diagnosis of small bowel (SB) Crohn's disease (CD). However, data on the clinical impact of VCE in patients with established CD are scarce. The aim of this study was to examine the impact and safety of VCE on the clinical management of patients with established CD. A retrospective, multicenter, cross-sectional study. The study cohort included consecutive patients with established SB CD who underwent VCE in 4 tertiary referral centers (1 Canada, 1 Sweden, and 2 United Kingdom) from January 2008 to October 2013. Patients were excluded if VCE was performed as a part of the initial diagnostic workup. The presence of SB mucosal inflammation was quantified using the Lewis score. Inflammatory biomarkers (C-reactive protein and fecal calprotectin) were measured and correlated with the Lewis score. The study included 187 patients. No SB inflammation was observed in 28.4%, mild-to-moderate inflammation in 26.6%, and moderate-to-severe inflammation in 45% of the patients (median Lewis score, 662; range, 0-6400). A change in management was recommended in 52.3% of the patients based on VCE findings. Elevated C-reactive protein, fecal calprotectin, or the combination of both were poorly correlated with significant SB inflammation. SB capsule retention occurred in 4 patients (2.1%). VCE in patients with established CD is safe, and the results often have a significant clinical impact. VCE should not be limited to CD patients with positive inflammatory markers because their predictive value for significant SB inflammation is poor.

Diagnose einer Magenperforation nach stumpfem Bauchtrauma mittels 18F-FDG PET-CT

Positron emission tomography with [(18)F]-fluorodeoxyglucose provides functional and anatomic information by visualising the uptake of radiolabelled glucose in tumour and inflammatory cells. We report delayed diagnosis of necrosis of the gastric fundus after blunt abdominal trauma in a 73-year-old man. After a car accident with head-on collision, the patient was stabilised in our emergency room. His femur was treated by internal fixation, his ellbow was stabilised by a fixateur externe. During surgery his status deteriorated. The patient was in need of high dosage of inotrops during the following days. He had a biventricular pacemaker implanted because of ischemic myocardiopathy, and he suffered from renal insufficiency. Over the next days, his haemodynamics improved. A central venous line had to be removed because of ensuing septic fever. The patient complained of upper abdominal pain and nausea. A sonography and computer tomography without contrast medium were performed with negative result. Because of contamination of the central venous line with Staphylococcus epidermidis the pacemaker was evaluated for infection by transoesophageal echocardiography, again without any findings. Because of ongoing fever and positive inflammatory markers a positron emission tomography was indicated, as a contrast examination and a magnetic resonance examination were not feasible because of the renal insufficiency and the pacemaker, respectively. Prophylactic removal of the pacemaker would have been a substantial risk for the patient due to his underlying myocardiopathy. Positron emission tomography showed an increased tracer uptake in the gastric fundus, which turned out to be necrotic by endoscopy. A laparoscopic resection followed, and drainage of an abscess, which had evolved subsequently between stomach and spleen stopped the inflammatory process. This case report demonstrates that positron emission tomography may be an alternative to computer tomography with contrast medium and magnetic resonance imaging to detect an inflammatory process in patients with pre-existing disease.

Gastrointestinal Manifestations of Henoch-Schoenlein Purpura

A 43-year-old Hispanic male was admitted to the hospital with a 2-week history of epigastric pain, hematochezia, rash, and joint pain in his elbows and knees. The pain was non-radiating, without nausea, vomiting, or exacerbating or alleviating factors. Two weeks prior to the onset of these symptoms he had developed flu-like symptoms that resolved without treatment. His past medical history was significant for hypertension; however, he had no personal or family history of gastrointestinal, hematological, or autoimmune disease. He had been taking hydrochlorothiazide and irbesartan for his hypertension. He did not smoke or drink alcohol. On admission, he was afebrile without any abnormalities in his vital signs or cardiopulmonary examination. Physical examination was notable for palpable petechial and purpuric lesions on his legs, arms, and periumbilical region; epigastric tenderness was elicited upon deep palpation, and his elbows and knees were tender to touch (Fig. 1). Stool occult blood was positive. Laboratory investigations revealed leukocytosis and positive inflammatory markers but without evidence of bacterial, infectious, or autoimmune process. Urine analysis did not reveal hematuria or proteinuria. A skin biopsy was reported as leukocytoclastic vasculitis. Computed tomography, performed at the referring outside hospital, revealed focal thickening of the third and fourth portions of the duodenum and proximal jejunum without signs of intussusception or pancreatic inflammation. An upper endoscopy revealed acute, moderately severe, patchy inflammation, as well as ulcerations and friability of the distal duodenum and jejunum. Duodenal and jejunal biopsies revealed benign small bowel mucosa with acute and chronic inflammation, ulceration and fragments of ulcer bed. Fungal Grocott methenamine silver staining was negative; no granulomas or viral changes were noted. A chest radiograph was normal. Colonoscopy revealed small non-bleeding vasculitic lesions and red erythematous plaques throughout the colon and the terminal ileum (Fig. 2). A small bowel capsule endoscopy, performed to evaluate the extent of gastrointestinal tract involvement, demonstrated scattered areas of erythematous ulcerated mucosa extending from the duodenum to the ileum (Fig. 3). His symptoms began to resolve within 2 days after admission without further treatment. His rash, diarrhea, abdominal pain, and joint pain steadily improved during his hospitalization. At follow-up 2 months later, he remained symptom-free; his urine screen for hematuria remained negative.

Diagnostic yield and clinical impact of wireless capsule endoscopy in patients with chronic abdominal pain with or without diarrhea: A Greek multicenter study

Background Wireless capsule endoscopy has become the gold standard for the examination of small bowel. However, its role in the evaluation of patients suffering from chronic abdominal pain is not yet clearly defined. We conducted an open-label prospective multi-center study to evaluate the yield and clinical outcome of capsule endoscopy in patients with chronic abdominal pain with/without diarrhea. Methods Seventy-two patients with chronic (> 3 months) abdominal pain with/without diarrhea in whom the underlying pathology could not be diagnosed by conventional modalities, underwent capsule endoscopy in either of the 6 participating centers. Patients were then followed up for clinical outcomes. Results The overall diagnostic yield of capsule endoscopy was 44.4%. More specifically, its diagnostic yield was 21.4% in patients with abdominal pain and negative inflammatory markers (C-reactive protein and erythrocyte sedimentation rate), 66.7% in patients with abdominal pain and positive inflammatory markers, 0% in patients with abdominal pain, diarrhea and negative inflammatory markers, and 90.1% in patients with abdominal pain, diarrhea and positive inflammatory markers. Both univariate and multivariate regression analyses showed that abnormal C-reactive protein and erythrocyte sedimentation rate were significant factors related with positive capsule endoscopy findings. Conclusions Chronic abdominal pain with/without diarrhea should be accompanied by elevated inflammatory markers to be regarded as a valid indication for capsule endoscopy. The yield of capsule endoscopy in such patients is reasonably high and clinical outcomes of patients treated with capsule endoscopy findings as a guide are significant.

Small-Bowel Capsule Endoscopy in Patients with Suspected Crohn's Disease—Diagnostic Value and Complications

Background. The aim of this work was to assess the value of capsule enteroscopy in the diagnosis of patients with suspected Crohn's Disease (CD). Methods. This was a retrospective study in a single tertiary care centre involving patients undergoing capsule enteroscopy for suspected CD. Patients taking nonsteroidal anti inflammatory drugs during the thirty preceding days or with a follow-up period of less than six months were excluded. Results. Seventy eight patients were included. The endoscopic findings included mucosal breaks in 50%, ulcerated stenosis in 5%, and villous atrophy in 4%. The diagnosis of CD was established in 31 patients. The sensitivity, specificity, positive and negative predictive value of the endoscopic findings were 93%, 80%, 77%, and 94%, respectively. Capsule retention occurred in four patients (5%). The presence of ulcerated stenosis was significantly more frequent in patients with positive inflammatory markers. The diagnostic yield of capsule enteroscopy in patients with negative ileoscopy was 56%, with a diagnostic acuity of 93%. Conclusions. Small bowel capsule endoscopy is a safe and valid technique for assessing patients with suspected CD. Capsule retention is more frequent in patients with positive inflammatory markers. Patients with negative ileoscopy and suspected CD should be submitted to capsule enteroscopy.

De novo LMNA mutations cause a new form of congenital muscular dystrophy

To describe a new entity of congenital muscular dystrophies caused by de novo LMNA mutations. Fifteen patients presenting with a myopathy of onset in the first year of life were subjected to neurological and genetic evaluation. Histopathological and immunohistochemical analyses were performed for all patients. The 15 patients presented with muscle weakness in the first year of life, and all had de novo heterozygous LMNA mutations. Three of them had severe early-onset disease, no motor development, and the rest experienced development of a "dropped head" syndrome phenotype. Despite variable severity, there was a consistent clinical pattern. Patients typically presented with selective axial weakness and wasting of the cervicoaxial muscles. Limb involvement was predominantly proximal in upper extremities and distal in lower extremities. Talipes feet and a rigid spine with thoracic lordosis developed early. Proximal contractures appeared later, most often in lower limbs, sparing the elbows. Ten children required ventilatory support, three continuously through tracheotomy. Cardiac arrhythmias were observed in four of the oldest patients but were symptomatic only in one. Creatine kinase levels were mild to moderately increased. Muscle biopsies showed dystrophic changes in nine children and nonspecific myopathic changes in the remaining. Markedly atrophic fibers were common, most often type 1, and a few patients showed positive inflammatory markers. The LMNA mutations identified appear to correlate with a relatively severe phenotype. Our results further broaden the spectrum of laminopathies and define a new disease entity that we suggest is best classified as a congenital muscular dystrophy (LMNA-related congenital muscular dystrophy, or L-CMD).