Lee, Ju-Yeun; Min, Ju-Hong; Han, Sueng-Han; Han, Jinu
We describe a 27-year-old pregnant female with new onset of conjugate gaze deficit during the third trimester of pregnancy. Repetitive nerve stimulation tests, neostigmine tests, and acetylcholine receptor antibody assays were all negative. The patient delivered a normal healthy baby at a local clinic via cesarean section. The baby became hypotonic and had respiratory failure several minutes after birth. The result of acetylcholine receptor antibody was negative in the neonate. The neonate became healthy spontaneously and was extubated after 21 days of ventilation care. Two months after delivery, the mother developed ptosis and generalized symptoms and subsequent workup revealed she was muscle specific kinase (MuSK) antibody positive. The neonate was presumed to have an anti-MuSK-mediated transient neonatal myasthenia gravis. Although MuSK antibody testing is rarely indicated in ocular myasthenia gravis, MuSK antibody testing is necessary in pregnant women who are presumed ocular myasthenia gravis to warn occurrence of transient neonatal myasthenia gravis. Copyright © 2017 Elsevier B.V. All rights reserved.
Full Text Available Abstract Background The myasthenia gravis is twice as common in women as in men and frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Generally, during pregnancy in one third of patients the disease exacerbates, whereas in two thirds it remains clinically unchanged. Complete remission can occur in some patients. Methods To describe the clinical course, delivery and neonatal outcome of 18 pregnant women with the diagnosis of myasthenia gravis. Retrospective chart review of pregnant patients with myasthenia gravis, followed at the National Institute of Perinatology in Mexico City over an 8-year period. Data was abstracted from the medical records on the clinical course during pregnancy, delivery and neonatal outcome. Results From January 1, 1996 to December 31, 2003 18 patients with myasthenia gravis were identified and included in the study. The mean ± SD maternal age was 27.4 ± 4.0 years. During pregnancy 2 women (11% had an improvement in the clinical symptoms of myasthenia gravis, 7 women (39% had clinical worsening of the condition of 9 other patients (50% remained clinically unchanged. Nine patients delivered vaginally, 8 delivered by cesarean section and 1 pregnancy ended in fetal loss. Seventeen infants were born at mean ± SD gestational age of 37.5 ± 3.0 weeks and a mean birth weight of 2710 ± 73 g. Only one infant presented with transient neonatal myasthenia gravis. No congenital anomalies were identified in any of the newborns. Conclusions The clinical course of myasthenia gravis during pregnancy is variable, with a significant proportion of patients experiencing worsening of the clinical symptoms. However, neonatal transient myasthenia was uncommon in our patient population.
Vrinten, C.; van der Zwaag, A.M.; Weinreich, S.S.; Scholten, R.J.; Verschuuren, J.J.
BACKGROUND: Myasthenia is a condition in which neuromuscular transmission is affected by antibodies against neuromuscular junction components (autoimmune myasthenia gravis, MG; and neonatal myasthenia gravis, NMG) or by defects in genes for neuromuscular junction proteins (congenital myasthenic
Braga, António Costa; Pinto, Clara; Santos, Ernestina; Braga, Jorge
We evaluated the clinical course during pregnancy and neonatal outcomes of a cohort of Portuguese women with myasthenia gravis (MG). Retrospective study. Twenty-five patients with 30 pregnancies were included. Mean maternal age was 32.4 ± 4.1 years. Miscarriage rate was 6.7%, with delivery of 28 newborns. Deterioration in MG during pregnancy occurred in 43.3%, and 46.4% occurred at postpartum. Eighty percent were medicated with pyridostigmine, 43.3% with corticosteroids, and 40% with intravenous immunoglobulin. There were no maternal or neonatal deaths. Mean gestational time at delivery was 38.2 weeks. No cases of fetal growth restriction, preeclampsia, preterm delivery, or fetal demise were observed. Global cesarean rate was 64.3%. Two newborns developed transient neonatal myasthenia. A high rate of clinical worsening of MG in the mother was observed in this retrospective study, which highlights the importance of a multidisciplinary approach for avoiding maternal adverse outcomes. Muscle Nerve 54: 715-720, 2016. © 2016 Wiley Periodicals, Inc.
Fargas-Berríos, N.; García-Fragoso, L.; García-García, I.; Valcárcel, M.
Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor ...
Transient neonatal diabetes and neonatal hyperglycaemia both present in the neonatal period with features of hyperglycaemia, dehydration and weight loss. Differentiating these conditions clinically is difficult. We describe the case of a 13 day old female whom we managed recently who could have had either condition.
Fargas-Berríos, N; García-Fragoso, L; García-García, I; Valcárcel, M
Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM) is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM) and transient neonatal diabetes mellitus (TNDM). We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL), glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate's hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.
Full Text Available Neonatal hyperglycemia is a metabolic disorder found in the neonatal intensive care units. Neonatal diabetes mellitus (NDM is a very uncommon cause of hyperglycemia in the newborn, occurring in 1 in every 400,000 births. There are two subtypes of neonatal diabetes mellitus: permanent neonatal diabetes mellitus (PNDM and transient neonatal diabetes mellitus (TNDM. We describe a term, small for gestational age, female neonate with transient neonatal diabetes mellitus who presented with poor feeding tolerance and vomiting associated with hyperglycemia (385 mg/dL, glycosuria, and metabolic acidosis within the first 12 hours of life. The neonate was treated with intravenous insulin, obtaining a slight control of hyperglycemia. An adequate glycemia was achieved at 5 weeks of life. The molecular studies showed complete loss of maternal methylation at the TND differentially methylated region on chromosome 6q24. The etiology of this neonate’s hyperglycemia was a hypomethylation of the maternal TND locus. A rare cause of neonatal diabetes mellitus must be considered if a neonate presents refractory hyperglycemia. To our knowledge, this is the first case reported in Puerto Rico of transient neonatal mellitus due to the uncommon mechanism of maternal hypomethylation of the TND locus. Its prevalence in Puerto Rico is unknown.
Full Text Available Transient neonatal pustular melanosis is mostly found in full-term black infants. It is a benign and self-limited disease, and the etiology is still unknown. We present a full-term female neonate with multiple vesiculopustular and pigmented macular lesions found immediately after her birth. A skin biopsy showed vesicles consisting of intracorneal and subcorneal aggregates of neutrophils, which is compatible with transient neonatal pustular melanosis. Although it is rare in Taiwan and Asian countries, transient neonatal pustular melanosis should always be considered when pustulosis is found in the neonatal period to prevent the use of unnecessary antibiotics. Dermatological consultation and histological confirmation are sometimes required for the final diagnosis.
Fan, Yi; Zhang, Qijun; Li, Hua; Cheng, Zijie; Li, Xing; Chen, Yumei; Shen, Yahui; Wang, Liansheng; Song, Guixian; Qian, Lingmei
Neonatal mouse hearts have completely regenerative capability after birth, but the ability to regenerate rapidly lost after 7 days, the mechanism has not been clarified. Previous studies have shown that mRNA profile of adult mouse changed greatly compared to neonatal mouse. So far, there is no research of peptidomics related to heart regeneration. In order to explore the changes of proteins, enzymes, and peptides related to the transient regeneration, we used comparative petidomics technique to compare the endogenous peptides in the mouse heart of postnatal 1 and 7 days. In final, we identified 236 differentially expressed peptides, 169 of which were upregulated and 67 were downregulated in the postnatal 1 day heart, and also predicted 36 functional peptides associated with transient regeneration. The predicted 36 candidate peptides are located in the important domains of precursor proteins and/or contain the post-transcriptional modification (PTM) sites, which are involved in the biological processes of cardiac development, cardiac muscle disease, cell proliferation, necrosis, and apoptosis. In conclusion, for the first time, we compared the peptidomics profiles of neonatal heart between postnatal 1 day and postnatal 7 day. This study provides a new direction and an important basis for the mechanism research of transient regeneration in neonatal heart. J. Cell. Biochem. 118: 2828-2840, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Resources - myasthenia gravis ... The following organizations provide information on myasthenia gravis : Myasthenia Gravis Foundation of America -- www.myasthenia.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih.gov/Disorders/Patient- ...
Towbin, Alexander J.; Fleck, Robert; Ying, Jun
A transient hepatic attenuation difference (THAD) is a hepatic perfusion anomaly seen on contrast-enhanced CT scans caused by an alteration in the dual blood supply of the liver. Although THADs have been described in adolescents and adults, they have not previously been described in neonates. We describe the appearance and evaluate the frequency of THADs in neonates ≤1 month of age compared to other infants younger than 2 years. A retrospective study was performed looking at all CT angiograms from 2000 to 2007 in infants <2 years of age. The incidence of THADs was compared among four age groups. Significance was determined using a logistic regression model. The study included 128 CT angiograms. A THAD was seen in 9/26 infants <1 month of age, in 3/50 infants 1 to 6 months of age, in 1/23 infants 6 months to 1 year of age, and in 1/29 infants 1 to 2 years of age. A THAD was found significantly more frequently in infants <1 month of age than in the older age groups (P<0.05). THADs are benign entities that can be seen normally in the neonatal age group. When the characteristic appearance is seen on CT, no further imaging is needed. (orig.)
Myasthenia gravis is a disease that causes weakness in your voluntary muscles. These are the muscles that ... gets worse with activity, and better with rest. Myasthenia gravis is an autoimmune disease. Your body's immune ...
... increase the risk of myasthenia gravis , but the identity of these genes is unknown. Many factors likely ... Myasthenia Gravis Fact Sheet MalaCards: myasthenia gravis Merck Manual Home Health Handbook for Patients and Caregivers Myasthenia ...
Barnett, Carolina; Merkies, Ingemar S J; Katzberg, Hans; Bril, Vera
The Quantitative Myasthenia Gravis Score and the Myasthenia Gravis Composite are two commonly used outcome measures in Myasthenia Gravis. So far, their measurement properties have not been compared, so we aimed to study their psychometric properties using the Rasch model. 251 patients with stable myasthenia gravis were assessed with both scales, and 211 patients returned for a second assessment. We studied fit to the Rasch model at the first visit, and compared item fit, thresholds, differential item functioning, local dependence, person separation index, and tests for unidimensionality. We also assessed test-retest reliability and estimated the Minimal Detectable Change. Neither scale fit the Rasch model (X2p Myasthenia Gravis Composite had lower discrimination properties than the Quantitative Myasthenia Gravis Scale (Person Separation Index: 0.14 and 0.7). There was local dependence in both scales, as well as differential item functioning for ocular and generalized disease. Disordered thresholds were found in 6(60%) items of the Myasthenia Gravis Composite and in 4(31%) of the Quantitative Myasthenia Gravis Score. Both tools had adequate test-retest reliability (ICCs >0.8). The minimally detectable change was 4.9 points for the Myasthenia Gravis Composite and 4.3 points for the Quantitative Myasthenia Gravis Score. Neither scale fulfilled Rasch model expectations. The Quantitative Myasthenia Gravis Score has higher discrimination than the Myasthenia Gravis Composite. Both tools have items with disordered thresholds, differential item functioning and local dependency. There was evidence of multidimensionality in the QMGS. The minimal detectable change values are higher than previous studies on the minimal significant change. These findings might inform future modifications of these tools.
... is passed from the blood into cells for conversion to energy. People with 6q24-related transient neonatal ... Related Information What does it mean if a disorder seems to run in my family? What is ...
Currier, R.D.; Routh, A.; Hickman, B.T.; Douglas, M.A.
Twenty-eight patients with progressive myasthenia gravis without thymoma received treatment of 3000 rads (30 Gy) to the anterior mediastinum, and a followup was conducted for five to 18 years. Twenty-four patients had generalized myasthenia, and four had ocular myasthenia gravis. Twenty patients with generalized myasthenia survived the several month post-treatment period and improved, but four died during that period. The improvement lasted a median of 1.5 years, and older patients had longer remissions than younger patients. The four patients who had ocular myasthenia did not change after treatment. Mediastinal irradiation produces a temporary remission in generalized myasthenia
Currier, R.D.; Routh, A.; Hickman, B.T.; Douglas, M.A.
Twenty-eight patients with progressive myasthenia gravis without thymoma received treatment of 3000 rads (30 Gy) to the anterior mediastinum, and a followup was conducted for five to 18 years. Twenty-four patients had generalized myasthenia, and four had ocular myasthenia gravis. Twenty patients with generalized myasthenia survived the several month post-treatment period and improved, but four died during that period. The improvement lasted a median of 1.5 years, and older patients had longer remissions than younger patients. The four patients who had ocular myasthenia did not change after treatment. Mediastinal irradiation produces a temporary remission in generalized myasthenia.
Cho, Sung Shick; Kim, Jung Hoon; Hong, Hyun Sook; Shin, Ji Hoon; Hwang, Jung Hwa; Goo, Dong Erk; Kwon, Kui Hyang; Choi, Deuk Lin
To evaluate the clinical significance of transient hyperechogenicity of the renal medulla in neonates by comparing the clinical features, urinalysis and follow-up ultrasonographic examination of the control group. One hundred ten neonates were divided into 2 groups, hyperechoic and normal renal medulla groups, and all of them underwent abdominal ultrasound with a 7.5 MHz linear transducer (Sonoace 8800MT, Medicine, Korea) from November 1999 to January 2000. Whether there was any difference in clinical features including birth weight, body surface area, gestational age, sex, date of examination and mode of delivery between two groups was evaluated. In addition, any difference in their urinary osmolarity, albumin, uric acid and calcium in 41 neonates who underwent urinalysis was evaluated. In ten neonates with hyperechoic renal medulla underwent follow-up study, the follow-up ultrasonographic findings were compared with the initial study. In 67 of 110 (61%) neonates, ultrasonography demonstrated hyperechoic renal medulla. There was no difference in clinical features between the hyperechoic renal medullary group and normal group. In 41 neonates, there was no significant difference in urinalysis between two groups. (Osmolarity=146.46 ± 68.4 mOsml/KgH 2 O in the hyperechoic renal medullary group vs. 149.8 ± 77.7 mOsml/KgH 2 O in the normal group; albumin=13.9 ± 10.2 mg/ml vs. 17.6 ± 13.6 mg/dl; uric acid=50.0 ± 23.3 mg/dl vs. 44.9 ± 34.1 mg/dl; calcium=1.38 ± 3.0 mg/ dl vs. 0.44 ± 0.07 mg/dl.) Ten neonates who underwent follow-up ultrasonography within 20 days after the initial study showed the normal medullary echogenicity. There were no significant difference between the hyperechoic renal medullary group and the normal echogenic group in their clinical features and urinalysis. Therefore, the hyperechoic renal medullar in neonate is considered as an usual and transient finding which disappears on follow-up study.
Full Text Available Background. Late transient neonatal hypocalcemia with hyperphosphatemia is potentially life-threatening. The use of dihydroxycholecalciferol in the management of neonatal hypocalcemia is unexplored. Objective. We hypothesized adding dihydroxycholecalciferol to intravenous continuous calcium infusion (CaI will achieve accelerated correction of hypocalcemia. Design/Methods. A controlled double-blind randomized placebo group was organized to compare the addition of dihydroxycholecalciferol to CaI in 3–14 day old neonates presenting with hypocalcemia, hyperphosphatemia and seizures. Ionized calcium and phosphorus were measured to adjust CaI and maintain eucalcemia. Time to resolution of hypocalcemia was defined as time from starting CaI to the first ionized calcium of mmol/L. CaI was discontinued when ionized calcium levels were mmol/L on two measurements and the infant tolerated feeds. Results. Fourteen neonates were studied without statistical difference between groups. Time to correction of hypocalcemia for 1,25 dihydroxycholecalciferol versus placebo was versus hours respectively (. The duration of CaI was versus hours respectively (. Conclusions. The addition of dihydroxycholecalciferol to standard CaI therapy reduced the duration of CaI, but did not reduce the time to correct hypocalcemia in neonates with late transient hypocalcemia.
Amaral, Jennifer M.; Abrams, Steve; Karaviti, Lefkothea; McKay, Siripoom V.
Background. Late transient neonatal hypocalcemia with hyperphosphatemia is potentially life-threatening. The use of dihydroxycholecalciferol in the management of neonatal hypocalcemia is unexplored. Objective. We hypothesized adding dihydroxycholecalciferol to intravenous continuous calcium infusion (CaI) will achieve accelerated correction of hypocalcemia. Design/Methods. A controlled double-blind randomized placebo group was organized to compare the addition of dihydroxycholecalciferol ...
Boonen, Susanne E; Mackay, Deborah J G; Hahnemann, Johanne M D
Transient neonatal diabetes mellitus 1 (TNDM1) is the most common cause of diabetes presenting at birth. Approximately 5% of the cases are due to recessive ZFP57 mutations, causing hypomethylation at the TNDM locus and other imprinted loci (HIL). This has consequences for patient care because...
Swick, H.M.; Preston, D.F.; McQuillen, M.P.
A study was conducted to determine whether 67 Ga scans could be used for the detection of thymomas and to investigate the activity of the thymus gland in patients with myasthenia gravis. Scans of the anterior mediastinum proved to be a reliable way to detect thymomas. The scans were positive in eight patients including three with myasthenia gravis and histologically proved thymomas, three others with severe myasthenia gravis and thymic tumors, and two with histologically proved thymomas not associated with myasthenia. Activity on 67 Ga scans was not directly related to the increased activity of the thymus gland that is presumed to be associated with myasthenia gravis
Swick, H.M. (Univ. of Kentucky, Lexington); Preston, D.F.; McQuillen, M.P.
A study was conducted to determine whether /sup 67/Ga scans could be used for the detection of thymomas and to investigate the activity of the thymus gland in patients with myasthenia gravis. Scans of the anterior mediastinum proved to be a reliable way to detect thymomas. The scans were positive in eight patients including three with myasthenia gravis and histologically proved thymomas, three others with severe myasthenia gravis and thymic tumors, and two with histologically proved thymomas not associated with myasthenia. Activity on /sup 67/Ga scans was not directly related to the increased activity of the thymus gland that is presumed to be associated with myasthenia gravis. (HLW)
Laborie, Lene Bjerke; Mackay, Deborah J G; Temple, I Karen; Molven, Anders; Søvik, Oddmund; Njølstad, Pål Rasmus
One known genetic mechanism for transient neonatal diabetes is loss of methylation at 6q24. The etiology of prune belly sequence is unknown but a genetic defect, affecting the mesoderm from which the triad abdominal muscle hypoplasia, urinary tract abnormalities, and cryptorchidism develop, has been suggested. We investigated a family, including one twin, with transient neonatal diabetes and prune belly sequence. Autoantibody tests excluded type 1 diabetes. Microsatellite marker analysis confirmed the twins being monozygotic. We identified no mutations in ZFP57, KCNJ11, ABCC8, GCK, HNF1A, HNF1B, HNF3B, IPF1, PAX4, or ZIC3. The proband had loss of methylation at the 6q24 locus TNDM and also at the loci IGF2R, DIRAS3, and PEG1, while the other family members, including the healthy monozygotic twin, had normal findings. The loss of methylation on chromosome 6q24 and elsewhere may indicate a generalized maternal hypomethylation syndrome, which accounts for both transient neonatal diabetes and prune belly sequence.
Erol, S.; Celik, I.H.; Demirel, N.
Methemoglobin (MetHb) is a form of hemoglobin which contains iron in ferric state. The delivery of oxygen to tissues is impaired and cellular hypoxia develops with an increase in MetHb levels. Methemoglobinemia is a rare but potentially lethal complication of local anesthetics. In this clinical brief, three cases of transient neonatal methemoglobinemia, caused by maternal pudendal anesthesia with prilocaine, are reported. (author)
Qi, Guo-Yan; Liu, Peng
Purpose. To evaluate the treatment effect and side effect of Shenqi Fuzheng Injection (SFI) on alleviating transient worsening of myasthenia gravis (MG) symptoms caused by high-dose steroids pulse therapy. Methods. Sixty-six consecutive patients with MG were randomly divided into two groups: the treatment group treated with SFI and methylprednisolone pulse therapy (MPT) and the control group treated with MPT alone. The severity of MG before, during, and after MPT and the duration of transient worsening (TW) were evaluated and compared with the clinical absolute scoring (AS) and relative scoring (RS) system. Results. Twenty-nine patients experienced TW in each group. At TW, the AS was significantly increased (P < 0.000) in both groups compared with baseline data, with the AS increase in the treatment group (16.8 ± 2) significantly smaller (P < 0.05) than in the control group (24.9 ± 2.5). At the end of the treatment course, the AS for the treatment group was significantly decreased (7.5 ± 0.9) compared with at TW, although no significant difference compared with the control (9.7 ± 1.1). The TW lasted 1–6 days (mean 3.7) for the treatment group, significantly shorter (P < 0.05) than 2–12 days (mean 7.8) for the control. The RS for the treatment group at the end of treatment was 43.8%–100% (mean 76.8% ± 2.6%), significantly better than the control group: 33.3%–100% (mean 67.2 ± 3.6%). Slight side effects (18.75%) included maldigestion and rash in the treatment group. Conclusion. SFI has a better treatment effect and few side effects and can alleviate the severity and shorten the duration of the transient worsening of MG during steroids pulse therapy. PMID:24348721
Myasthenia gravis is a rare long-term neurological condition that is characterised by fluctuating skeletal muscle weakness and fatigue, as well as respiratory difficulties. It is both an acquired autoimmune disease and a chronic neuromuscular disorder. Because of its rarity, myasthenia gravis is relatively unknown and may be unfamiliar to many nurses. While there are various types of myasthenia, this article focuses on myasthenia gravis, exploring its symptoms, diagnosis and treatment, and examining the nurse's role in managing the condition. The symptoms of myasthenic crisis and cholinergic crisis are also explained, and the experience of patients with myasthenia gravis in hospital and community settings is illustrated using case studies.
Chang, Elaine; Sabichi, Anita L; Sada, Yvonne H
Checkpoint inhibitors have become standard therapy for multiple cancers, and their use will increase in the next year as regulatory approvals for additional indications are expected. It is essential for clinicians to be aware of the potential for rare immune-related adverse effects. Here, we report the case of a new diagnosis of myasthenia gravis (MG) after the use of nivolumab for squamous cell carcinoma of the bladder. A review the literature identified 10 cases of MG diagnosed after programmed cell death protein 1 inhibitor therapy. This is the first case, to our knowledge, reported in association with bladder cancer. The precise diagnosis of MG has important implications on management, as treatment with steroids can transiently worsen myasthenia in nearly 50% of cases.
Full Text Available Background. Late transient neonatal hypocalcemia with hyperphosphatemia is potentially life-threatening. The use of 1.25 dihydroxycholecalciferol in the management of neonatal hypocalcemia is unexplored. Objective. We hypothesized adding 1.25 dihydroxycholecalciferol to intravenous continuous calcium infusion (CaI will achieve accelerated correction of hypocalcemia. Design/Methods. A controlled double-blind randomized placebo group was organized to compare the addition of 1.25 dihydroxycholecalciferol to CaI in 3–14 day old neonates presenting with hypocalcemia, hyperphosphatemia and seizures. Ionized calcium and phosphorus were measured to adjust CaI and maintain eucalcemia. Time to resolution of hypocalcemia was defined as time from starting CaI to the first ionized calcium of ≥1.1 mmol/L. CaI was discontinued when ionized calcium levels were ≥1.1 mmol/L on two measurements and the infant tolerated feeds. Results. Fourteen neonates were studied without statistical difference between groups. Time to correction of hypocalcemia for 1,25 dihydroxycholecalciferol versus placebo was 7.2 ± 1.9 versus 11.5 ± 3.4 hours respectively (p=.26. The duration of CaI was 15.0 ± 1.5 versus 24.8 ± 4.4 hours respectively (p=.012. Conclusions. The addition of 1.25 dihydroxycholecalciferol to standard CaI therapy reduced the duration of CaI, but did not reduce the time to correct hypocalcemia in neonates with late transient hypocalcemia.
O.Ye. Abaturov; A.O. Nikulina; O.O. Rusakova; I.O. Hirina; N.M. Lybenko
The article presents the differential diagnosis of diseases that occur with neonatal hyperglycemia. The common causes of neonatal hypoglycemia, variants of its combination with clinical manifestations from the various organs and systems are indicated. There was presented an algorithm for the choice of therapeutic measures in transient neonatal diabetes mellitus (TNDM). The features of diet in newborns, insulin therapy and other directions of drug treatment were described. There was provided t...
Renard, Dimitri; Hedayat, Amir; Gagnard, Corinne
Laryngeal myasthenia gravis is a relatively rare variant of myasthenia gravis. A vast portion of patients with initial laryngeal myasthenia gravis develop involvement of ocular and/or extra-ocular muscles during the years after symptom onset although a minority of laryngeal myasthenia gravis patients continues to have isolated laryngeal muscle involvement for several years. We present a 58-year-old woman with recurrent episodic isolated dysphonia (associated with diffuse bilateral vocal cord paresis on laryngoscopy) since the age of 32. Dysphonia became permanent since 6 months. A diagnosis of laryngeal myasthenia gravis was made based on abnormal single-fiber electromyography and spectacular response to pyridostigmine treatment. Repetitive nerve stimulation was normal and anti-acetylcholine receptor and anti-muscle specific tyrosine kinase antibodies were absent. This case shows that laryngeal myasthenia gravis can be isolated during 26 years of follow-up. We propose that even when myasthenia gravis seems unlikely as underlying mechanism of isolated dysphonia (because of lack of antibodies, normal repetitive nerve stimulation, and absence of extra-laryngeal involvement after years of follow-up), single-fiber electromyography should be performed and myasthenia gravis treatment should be tried. Copyright © 2014 Elsevier B.V. All rights reserved.
Wang, Lili; Zhang, Yun; He, Maolin
Clinical predictors for myasthenia gravis relapse and ocular myasthenia gravis secondary generalization during the first two years after disease onset remain incompletely identified. This study attempts to investigate the clinical predictors for the prognosis of Myasthenia Gravis. Eighty three patients with myasthenia gravis were concluded in this study. Baseline characteristics were analyzed as predictors. Relapse of myasthenia gravis developed in 26 patients (34%). Generalization developed in 34 ocular myasthenia gravis patients (85%). Other autoimmune diseases were observed more commonly in relapsed myasthenia gravis (P = 0.012). Second generalization group contained more late onset patients (P = 0.021). Ocular myasthenia gravis patients with thymus hyperplasia progressed more rapidly than those with other thymus pathology (P = 0.027). Single onset symptom of ocular myasthenia gravis such as ptosis or diplopia predicted early progression than concurrence of ptosis and diplopia (P = 0.027). Treatment effect including glucocorticoid, pyridostigmine, thymectomy, IVIG, immunosuppressive drugs did not show significant difference between the relapsed and non-relapsed groups. The treatment outcome also showed no difference between the single OMG and second generalized groups. Occurrence of associated autoimmune disease can serve as a potential predictor for myasthenia gravis relapse. Either ptosis or diplopia, as well as thymic hyperplasia can predict generalization in the first six months.
... are individualized There are many effective treatments for myasthenia gravis. Spontaneous improvement and even remission (although uncommon) ... Created by Kellen Interactive Web Design © copyright 2010 Myasthenia Gravis Foundation of America, Inc.
Weijnen, FG; Kuks, JBM; van der Glas, HW; Oudenaarde, [No Value; Bosman, F
Masticatory muscle electromyograms (EMGs) were recorded while patients with bulbar myasthenia gravis chewed artificial food and compared with those of patients with ocular myasthenia gravis, patients in clinical remission who had previously suffered from bulbar myasthenia gravis and healthy
Weijnen, FG; Kuks, JBM; van der Glas, HW; Wassenberg, MWM; Bosman, F
Objectives - The aim was to study tongue force in patients with bulbar myasthenia gravis and compare it with that of patients with ocular myasthenia gravis, patients in clinical remission who previously suffered from bulbar myasthenia gravis, and healthy subjects. Material and methods - Tongue force
MYASTHENIA GRAVIS MEDICATION INFORMATION CARD Drugs to be Avoided or Used with Caution in MG My Name _______________________________________________ ... the MGFA web site; reference document “Medications and Myasthenia Gravis (A Reference for Health Care Professionals.” www. ...
... Many different drugs have been associated with worsening myasthenia gravis (MG). However, these drug associations do not ... review article for health professionals, found at the myasthenia.org website. For this app, we are only ...
Ralli, Massimo; Altissimi, Giancarlo; Di Stadio, A; Mazzei, Filippo; Turchetta, Rosaria; Cianfrone, Giancarlo
There is increasing evidence of a connection between hearing function and myasthenia gravis (MG). Studies of the pathophysiological basis of this relationship suggest that acetylcholine receptors (AChRs) on outer hair cells (OHCs) play a central role. In patients with MG, autoantibodies against AChRs induce a progressive loss of AChRs on OHCs, decreasing their electromotility. The stapedial reflex decay test can be altered in MG patients, and can be used as an additional tool for diagnosis and monitoring. Transient evoked and distortion product otoacoustic emissions are the main diagnostic tool for monitoring OHC functionality in MG patients, and can be used to record subclinical hearing alterations before the onset of clinically evident hearing loss. Understanding the association between MG and hearing dysfunction requires a multidisciplinary approach. Otolaryngologists should take this relationship into account when approaching patients with a diagnosis of myasthenia gravis and "in patients with MG" with ण128;in MG patients, and the progress of hearing alterations should always be monitored in patients with MG.
Jagathesan, Tania; O'Brien, Michael D
Myasthenia gravis is an autoimmune condition where antibodies form against the acetylcholine receptors at the neuromuscular junction, eventually causing damage to the motor end plate. The clinical features include muscle fatigability as well as ocular, bulbar, and limb weakness, which can have implications on the role of a pilot or air traffic controller. This retrospective study reviewed the United Kingdom Civil Aviation Authority (UK CAA) experience of myasthenia gravis. A search of the United Kingdom Civil Aviation Authority medical records database from 1990 to 2016 identified 11 individuals with a diagnosis of myasthenia gravis. Data were extracted for the class of medical certificate, age at diagnosis, symptoms, acetylcholine receptor antibody status, treatment, the time from diagnosis to loss of medical certification, and the reasons for loss of certification. There were two Class 1 certificate holders (for professional flying) and six Class 2 certificate holders (for private pilot flying) and three air traffic controllers. The mean and median ages at diagnosis were 53 and 57 yr, respectively, with a range of 28-67 yr. The mean and median intervals from diagnosis to loss of certification were 22 and 11 mo, respectively, with a range of 0 to 108 mo. The aeromedical implications of myasthenia gravis, including complications, types of treatment, and functional impact, are considered. A policy for medical certification following a diagnosis of myasthenia gravis is proposed.Jagathesan T, O'Brien MD. Myasthenia gravis and its aeromedical implications. Aerosp Med Hum Perform. 2017; 88(1):30-33.
Full Text Available The article presents the differential diagnosis of diseases that occur with neonatal hyperglycemia. The common causes of neonatal hypoglycemia, variants of its combination with clinical manifestations from the various organs and systems are indicated. There was presented an algorithm for the choice of therapeutic measures in transient neonatal diabetes mellitus (TNDM. The features of diet in newborns, insulin therapy and other directions of drug treatment were described. There was provided the information about medical funds of this syndrome, which can be used in the organization of the diagnosis and treatment in children with 6q24-TNDM.
Full Text Available Ocular myasthenia gravis is an autoimmune disorder of the neuromuscular junction. Diplopia and ptosis are common symptoms at the onset of ocular myasthenia gravis. It may occur due to the antibodies developed against various drugs. We are reporting a case of ocular myasthenia gravis which was developed in a patient post angiography which may be due to antibody developed against the dye used in angiography.
Isabela Freixo Côrtes-Andrade
Full Text Available OBJETIVO: avaliar a sensibilidade e a especificidade de um equipamento automático de Emissão Otoacustica Evocada Transiente que utiliza um estímulo de banda estreita, Narrow. MÉTODOS: foi analisado o resultado da Triagem Auditiva Neonatal de 300 neonatos. A Emissão Otoacústica Evocada Transiente foi realizada com um equipamento portátil automático, com o estímulo de banda estreita - Narrow. Todos os neonatos foram submetidos ao Potencial Evocado Auditivo de Tronco Encefálico com o estímulo clique, duração 100μs como padrão-ouro. RESULTADOS: o percentual de "passa" na Triagem Auditiva Neonatal foi de 90,7%. Considerando os resultados do padrão-ouro, foi observado uma taxa de falso-positivo de 9%. A sensibilidade e especificidade encontradas foram de 100% e 92%, respectivamente. CONCLUSÃO: o estímulo de banda estreita - Narrow mostrou-se eficaz para ser utilizado nos programa de Triagem Auditiva Neonatal Universal.
María Bárbara Eizaguirre; Florencia Aguirre; Cecilia Yastremiz; Sandra Vanotti; Andrés Villa
Myasthenia gravis is a chronic autoimmune disease that affects the neuromuscular transmission. Controversial findings had been reported about cognitive impairment in this disease. The aim of this study was to investigate the cognitive pattern of patients with myasthenia gravis. There were enrolled 24 patients with myasthenia gravis, anti-acetylcholine receptor antibodies (ACRA) positive, and 24 healthy controls. Patients: age 43.9 ± 14.8, years of education 10.9 ± 3.3. Controls: age 44.5 ± 15...
Mourão, Aline Mansueto; Gomez, Rodrigo Santiago; Barbosa, Luiz Sergio Mageste; Freitas, Denise da Silva; Comini-Frota, Elizabeth Regina; Kummer, Arthur; Lemos, Stella Maris Aguiar; Teixeira, Antonio Lucio
The aims of the current study were 1) to evaluate the reliability and validity of the Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale and 2) to investigate the quality of life of Brazilian patients with myasthenia gravis and its determinants. This cross-sectional study included 69 patients with myasthenia gravis who underwent neurological evaluation and completed questionnaires regarding quality of life (the 36-item Short Form of the Medical Outcomes Study and the 15-item Myasthenia Gravis Quality of Life Scale), anxiety and depressive symptoms. The Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale showed high internal consistency and good concurrent validity with the 36-item Short Form of the Medical Outcomes Study and its subscales. Determinants of quality of life in Brazilian patients with myasthenia gravis included the current status of myasthenia gravis as assessed by the Myasthenia Gravis Composite, the current prednisone dose and the levels of anxiety and depression. The Brazilian version of the 15-item Myasthenia Gravis Quality of Life Scale is a valid instrument. Symptom severity, prednisone dosage and anxiety and depression levels impact the quality of life of patients with myasthenia gravis.
... of myasthenia are due to problems in the communication between nerve cells and muscles. Most involve the activities of neurotransmitters. Neurotransmitters are chemicals that allow neurons to relay information from one cell to the ...
Gilhus, Nils Erik; Verschuuren, Jan J
Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis. Copyright © 2015 Elsevier Ltd. All rights reserved.
... that medications can be discontinued. In a few cases, the severe weakness of myasthenia gravis may cause respiratory failure, which requires immediate emergency medical care. Clinical Trials Throughout the U.S. and Worldwide NINDS Clinical ...
Leon-Sarmiento, Fidias E; Leon-Ariza, Juan S; Prada, Diddier; Leon-Ariza, Daniel S; Rizzo-Sierra, Carlos V
Myasthenia gravis is a paradigmatic muscle disorder characterized by abnormal fatigue and muscle weakness that worsens with activities and improves with rest. Clinical and research studies done on nicotinic acetylcholine receptors have advanced our knowledge of the muscle involvement in myasthenia. Current views still state that sensory deficits are not "features of myasthenia gravis". This article discusses the gap that exists on sensory neural transmission in myasthenia that has remained after >300years of research in this neurological disorder. We outline the neurobiological characteristics of sensory and motor synapses, reinterpret the nanocholinergic commonalities that exist in both sensory and motor pathways, discuss the clinical findings on altered sensory pathways in myasthenia, and propose a novel way to score anomalies resulting from multineuronal inability associated sensory troubles due to eugenic nanocholinergic instability and autoimmunity. This medicine-based evidence could serve as a template to further identify novel targets for studying new medications that may offer a better therapeutic benefit in both sensory and motor dysfunction for patients. Importantly, this review may help to re-orient current practices in myasthenia. Copyright © 2016 Elsevier B.V. All rights reserved.
Dong Hyun Seo
Full Text Available The actual incidence of multiple thymoma is unknown and rarely reported because it remains controversial whether the cases represent a disease of multicentric origin or a disease resulting from intrathymic metastasis. In this case, a patient underwent total thymectomy for multiple thymoma with myasthenia gravis via bilateral video-assisted thoracic surgery. A well-encapsulated multinodular cystic mass, measuring 57 mm×50 mm×22 mm in the right lobe of the thymus, and a well-encapsulated mass, measuring 32 mm×15 mm×14 mm in the left lobe, were found. Both tumors were type B2 thymoma. Few cases of multiple thymoma with myasthenia gravis have ever been reported in the literature. We report a case of synchronous multiple thymoma associated with myasthenia gravis.
This patent describes an improvement in a process for diagnosing myasthenia gravis. The process comprises the steps of preparing a complex of acetycholine receptor protein, toxin and a radioactive isotope, incubating the complex with a serum sample from a patient so as to join antibodies engendered in connection with myasthenia gravis to the complex, precipitating the complex joined with antibody with anti-immunoglobulin and measuring radioactivity, from the radioactive isotope, of the precipitated complex. The improvement is that the acetylcholine receptor protein is derived from cells of the TE671 Line
This patent describes an improvement in a process for diagnosing myasthenia gravis. The process comprises the steps of preparing a complex of acetycholine receptor protein, toxin and a radioactive isotope, incubating the complex with a serum sample from a patient so as to join antibodies engendered in connection with myasthenia gravis to the complex, precipitating the complex joined with antibody with anti-immunoglobulin and measuring radioactivity, from the radioactive isotope, of the precipitated complex. The improvement is that the acetylcholine receptor protein is derived from cells of the TE671 Line.
... Institutes of Health (NIH), the leading supporter of biomedical research in the world. Although there is no cure ... understand the fundamental processes in neuromuscular development. This research could reveal new therapies for neuromuscular diseases like myasthenia gravis. Researchers are ...
Spasojevic, Ivana; Hajdukovic, Danica; Komarcevic, Milena; Petrovic, Stanislava; Jovanovic, Jelena; Ciric, Aleksandra
Myasthenia gravis is an autoimmune disease caused by antibodies leading to the destruction of nicotinic acetylcholine receptors on the neuromuscular junction. It is characterized by muscle weakness that gets aggravated with physical activity and improves at rest. Myasthenia Gravis Foundation of America made the clinical classification of Myasthenia gravis which is still in use today. "Tensilon test" is still the gold standard for the diagnosis of Myasthenia gravis. In addition to this test repeated muscular stimulation can be used as well as the analysis of specific autoantibodies. Treatment of Myasthenia Gravis. In conservative treatment of Mysthenia gravis anticholinesterases, immunosuppressants and plasmapheresis can be used. If conservative treatment does not lead to the desired remission, surgical treatment is indicated. The most accepted indication for thymectomy is the presence of thymoma with generalized form of Myasthenia gravis in adults. How to Distinguish Myasthenic From Cholinergic Crisis.'The following is important to make a difference between these two crises: knowledge of the events that preceded the crisis, the size of pupils as well as the presence of muscarinic signs and tensilon test. Specific Features of Anesthesia in Patients with Myasthienia Gravis. Mechanism of the disease development is the reason'for the increased sensitivity or resistance of these patients to certain types of drugs used in anesthesia. Protocol of Perioperative Anesthesia in Patients with Myasthenia Gravis. Based on 35 years of experience in the surgical treatment of patients with Myasthenia gravis anesthesiologists at the Department of Thoracic Surgery, Institute for Pulmonary Diseases of Vojvodina. made the protocol of anesthesia and perioperative treatment for these patients. Anesthesiologists may have to deal with a patient with myasthenia gravis in different types of surgical interventions. The protocol for anesthesia and perioperative management of these patients
Bak, Mads; Boonen, Susanne E; Dahl, Christina
of developing diabetes mellitus type 2 later in life. Transient neonatal diabetes mellitus 1 is caused by overexpression of the maternally imprinted genes PLAGL1 and HYMAI on chromosome 6q24. One of the mechanisms leading to overexpression of the locus is hypomethylation of the maternal allele of PLAGL1......BACKGROUND: Transient neonatal diabetes mellitus 1 (TNDM1) is a rare imprinting disorder characterized by intrautering growth retardation and diabetes mellitus usually presenting within the first six weeks of life and resolves by the age of 18 months. However, patients have an increased risk...... and HYMAI. A subset of patients with maternal hypomethylation at PLAGL1 have hypomethylation at additional imprinted loci throughout the genome, including GRB10, ZIM2 (PEG3), MEST (PEG1), KCNQ1OT1 and NESPAS (GNAS-AS1). About half of the TNDM1 patients carry mutations in ZFP57, a transcription factor...
Pedersen, E G; Hallas, Jesper; Hansen, K
BACKGROUND: An increase in late-onset myasthenia gravis (MG) has been reported. There are few large population-based studies over longer periods of time reflecting recent developments in MG incidence. METHODS: We identified a nationwide cohort of patients with incident myasthenia in Denmark in 1996...
Yoo, Yung Ju; Han, Sang Beom; Yang, Hee Kyung; Hwang, Jeong-Min
Ocular myasthenia gravis is a localized form of myasthenia gravis, which is a postsynaptic disorder of the neuromuscular junction that causes fluctuating weakness of extraocular muscles resulting from autoimmune mechanisms. In women with myasthenia, changes in sex hormone levels and administration of corticosteroids can trigger or worsen symptoms of myasthenia gravis. To describe a case of seronegative ocular myasthenia gravis whose first symptom appeared a day after in vitro fertilization procedure. A 37-year-old woman suddenly developed mild ptosis and fluctuating diplopia that worsened in the evening. Before the development of symptoms, she had undergone in vitro fertilization procedure and had taken oral steroids. Ocular motility examination revealed an intermittent exotropia in primary gaze at both distance and near. The neostigmine test confirmed her diagnosis as ocular myasthenia gravis. When taking a history for young women with sudden onset of binocular diplopia, steroids and sex hormones should be taken into account, which may trigger or exacerbate symptoms of ocular myasthenia gravis.
Full Text Available Ocular myasthenia gravis in conjunction with thyroid disorders, although rare, has been reported in the past. However, the similarity in the presentation of both the entities and the tendency of myasthenia gravis to get overlooked easily, even by experienced clinicians, necessitates a thorough knowledge, a strong consideration, and a vigilant approach, to aid in its diagnosis. We discuss a case of a female in a thyrotoxic state, with symptoms of ocular myasthenia gravis, and a brief overview of this entity.
Poornima A Shah
Full Text Available Man-in-the-barrel syndrome (MBS is an uncommon presentation due to bilateral, predominantly proximal muscle weakness that has not been described to be associated with myasthenia gravis. We describe a case of myasthenia gravis presenting as MBS. Additionally, he had significant wasting of the deltoids bilaterally with fibrillations on electromyography (EMG at rest and brief duration (3-6 ms bi/triphasic motor unit potentials (MUPs on submaximal effort apart from a decremental response on repetitive nerve stimulation (RNS at 2 Hz. While electrophysiology is an important tool in the diagnosis of myasthenia gravis, pathological EMG patterns do not exclude the diagnosis of myasthenia gravis.
Shah, Poornima A; Wadia, Pettarusp Murzban
Man-in-the-barrel syndrome (MBS) is an uncommon presentation due to bilateral, predominantly proximal muscle weakness that has not been described to be associated with myasthenia gravis. We describe a case of myasthenia gravis presenting as MBS. Additionally, he had significant wasting of the deltoids bilaterally with fibrillations on electromyography (EMG) at rest and brief duration (3-6 ms) bi/triphasic motor unit potentials (MUPs) on submaximal effort apart from a decremental response on repetitive nerve stimulation (RNS) at 2 Hz. While electrophysiology is an important tool in the diagnosis of myasthenia gravis, pathological EMG patterns do not exclude the diagnosis of myasthenia gravis. PMID:27011638
This is a 10 year retrospective review of patients managed at the Ahmadu Bello Teaching hospital, Zaria, Nigeria for myasthenia gravis. Only 4 patients were identified from the hospitals records. Myasthenia gravis appears uncommon in this environment. Reasons for the apparent rarity of this condition and other ...
José Lamartine de Assis
Full Text Available Two pairs of siblings with myasthenia gravis, belonging to two different families, are reported. This is the only record of familial myasthenia during the past twenty years, in a total of 145 patients seen at the Neurological Clinic of the São Paulo Medical School. In spite of the fact that myasthenia gravis does not show hereditary characteristics, the peculiar features of the four cases justify the present report. The two pairs of siblings were born from non myasthenic nor consanguineous parents. The disease started at birth showing bilateral partial eyelid ptosis in all patients. The course of the illness has been favorable. There was no thymoma.
Wolfe, Gil I; Kaminski, Henry J; Aban, Inmaculada B; Minisman, Greg; Kuo, Hui-Chien; Marx, Alexander; Ströbel, Philipp; Mazia, Claudio; Oger, Joel; Cea, J Gabriel; Heckmann, Jeannine M; Evoli, Amelia; Nix, Wilfred; Ciafaloni, Emma; Antonini, Giovanni; Witoonpanich, Rawiphan; King, John O; Beydoun, Said R; Chalk, Colin H; Barboi, Alexandru C; Amato, Anthony A; Shaibani, Aziz I; Katirji, Bashar; Lecky, Bryan R F; Buckley, Camilla; Vincent, Angela; Dias-Tosta, Elza; Yoshikawa, Hiroaki; Waddington-Cruz, Márcia; Pulley, Michael T; Rivner, Michael H; Kostera-Pruszczyk, Anna; Pascuzzi, Robert M; Jackson, Carlayne E; Garcia Ramos, Guillermo S; Verschuuren, Jan J G M; Massey, Janice M; Kissel, John T; Werneck, Lineu C; Benatar, Michael; Barohn, Richard J; Tandan, Rup; Mozaffar, Tahseen; Conwit, Robin; Odenkirchen, Joanne; Sonett, Joshua R; Jaretzki, Alfred; Newsom-Davis, John; Cutter, Gary R
Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone. We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone. Patients 18 to 65 years of age who had generalized nonthymomatous myasthenia gravis with a disease duration of less than 5 years were included if they had Myasthenia Gravis Foundation of America clinical class II to IV disease (on a scale from I to V, with higher classes indicating more severe disease) and elevated circulating concentrations of acetylcholine-receptor antibody. The primary outcomes were the time-weighted average Quantitative Myasthenia Gravis score (on a scale from 0 to 39, with higher scores indicating more severe disease) over a 3-year period, as assessed by means of blinded rating, and the time-weighted average required dose of prednisone over a 3-year period. A total of 126 patients underwent randomization between 2006 and 2012 at 36 sites. Patients who underwent thymectomy had a lower time-weighted average Quantitative Myasthenia Gravis score over a 3-year period than those who received prednisone alone (6.15 vs. 8.99, Pmyasthenia gravis. (Funded by the National Institute of Neurological Disorders and Stroke and others; MGTX ClinicalTrials.gov number, NCT00294658.).
Rivner, Michael H; Pasnoor, Mamatha; Dimachkie, Mazen M; Barohn, Richard J; Mei, Lin
Around 20% of patients with myasthenia gravis are acetylcholine receptor antibody negative; muscle-specific tyrosine kinase antibodies (MuSK) were identified as the cause of myasthenia gravis in 30% to 40% of these cases. Anti MuSK myasthenia gravis is associated with specific clinical phenotypes. One is a bulbar form with fewer ocular symptoms. Others show an isolated head drop or symptoms indistinguishable from acetylcholine receptor-positive myasthenia gravis. These patients usually respond well to immunosuppressive therapy, but not as well to cholinesterase inhibitors. Other antibodies associated with myasthenia gravis, including low-density lipoprotein receptor-related protein 4, are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.
Kirzinger, Lukas; Khomenko, Andrei; Schulte-Mattler, Wilhelm; Backhaus, Roland; Platen, Sabine; Schalke, Berthold
Adult and pediatric patients suffering from MuSK (muscle-specific kinase) -antibody positive myasthenia gravis exhibit similar features to individuals with acetylcholine receptor (AChR) antibodies, but they differ in several characteristics such as a predominant bulbar, respiratory and neck weakness, a generally worse disease severity and a tendency to develop muscle atrophy. Muscle atrophy is a rare phenomenon that is usually restricted to the facial muscles. We describe a girl with MuSK-antibody positive myasthenia gravis who developed a myopathy with severe generalized muscular weakness, muscle atrophy, and myopathic changes on electromyography. This is the first published example of a generalized myopathic syndrome in myasthenia gravis. We review the relevant literature and discuss the hypothesis of a mitochondrial myopathy as a pathogenic mechanism in MuSK-antibody positive myasthenia gravis. Copyright Â© 2016 Elsevier Inc. All rights reserved.
Weijnen, FG; Wokke, JHJ; Kuks, JBM; van der Glas, HW; Bosman, F
Masticatory muscle strength was quantified in patients with bulbar myasthenia gravis and compared with that of patients with ocular myasthenia gravis, patients in clinical remission (whether or not pharmacological) who previously suffered from bulbar myasthenia gravis, and healthy subjects. Maximal
Richards, Jason; Howard, James F
Myasthenia gravis (MG) is generally caused by antibodies directed against the neuromuscular junction, including antibodies against the postsynaptic nicotinic acetylcholine receptor (AChR). Pathologic abnormalities of the thymus gland, including thymoma, are associated with MG. We report a 56-year-old woman who presented with double vision. Single fiber EMG confirmed myasthenia gravis. AChR, striational muscle and MuSK antibodies were absent in the serum. Chest CT demonstrated a malignant thymoma. We report the first case of seronegative myasthenia gravis associated with malignant thymoma. The case challenges the conventional wisdom that all patients with thymoma associated MG test positive for antibodies against AChR. Copyright © 2017 Elsevier B.V. All rights reserved.
Kosachev, V D; Alekseeva, T M; Khalmurzina, A N
In the present work the results of the clinic-epidemiological analysis of 223 patients with the onset of the myasthenia at 60 y. o. and later, admitted and treated in the clinic of neurology for the passed 25years are represented. A dynamic growth of incidence of the late-onset myasthenia through the passed 10 years was administered. We administered a prevalence of the generalized form of the myasthenia gravis (61,5 %). The whole clinical table of the myasthenia was developed during an year in 76,7 % of the cases. A wide range of the concomitant somatic pathology in this group of the patients (especially, with a cardio-vascular pathology - 93,3 %) was found to worsen the course of the myasthenia itself. We found that the set of the therapeutic measures in myasthenia in the elderly is determined by the course of the myasthenia and the multiple organ failure due to the concomitant diseases. The scheme of complex corrective therapy of myasthenia gravis in elderly was developed.
Bettini, Mariela; Gonorazky, Hernan; Chaves, Marcelo; Fulgenzi, Ernesto; Figueredo, Alejandra; Christiansen, Silvia; Cristiano, Edgardo; Bertini, Enrico S; Rugiero, Marcelo
Cases of acquired rippling muscle disease in association with myasthenia gravis have been reported. We present three patients with iRMD (immune-mediated rippling muscle disease) and AChR-antibody positive myasthenia gravis. None of them had thymus pathology. They presented exercise-induced muscle rippling combined with generalized myasthenia gravis. One of them had muscle biopsy showing a myopathic pattern and a patchy immunostaining with caveolin antibodies. They were successfully treated steroids and azathioprine. The immune nature of this association is supported by the response to immunotherapies and the positivity of AChR-antibodies. Copyright © 2016 Elsevier B.V. All rights reserved.
March, Katherine L; Samarin, Michael J; Sodhi, Amik; Owens, Ryan E
Purpose Pembrolizumab, a monoclonal antibody which inhibits the programmed cell death 1 receptor, has been shown to efficaciously enhance pre-existing immune responses to malignancies. However, safety concerns must also be considered as pembrolizumab use has been associated with several life-threatening immune-related adverse events (irAEs). We report a fatal case of pembrolizumab-induced myasthenia gravis in a patient with no prior myasthenia gravis history. Case report A 63-year-old male presented with right eyelid drooping, puffiness, blurred vision, and shortness of breath two weeks after an initial infusion of pembrolizumab. He was subsequently diagnosed with new onset acetylcholine-receptor positive myasthenia gravis. Despite aggressive treatment with corticosteroids, pyridostigmine, intravenous immunoglobulin, and plasmapheresis, the patient clinically deteriorated and ultimately expired from acute respiratory failure after a 12-day hospitalization. Discussion Current package labeling for pembrolizumab warns against various irAEs associated with its use including pneumonitis, colitis, and endocrinopathies. To date, only one case of new onset myasthenia gravis and two case reports of myasthenia gravis exacerbation have been identified. This case further highlights the mortality risk associated with development of irAEs. Conclusion While rare, evidence for the development of MG associated with pembrolizumab is growing. Prompt recognition of symptoms and discontinuation of pembrolizumab is necessary to help improve prognosis.
BACK GROUND: Myasthenia gravis (MG) is generally a rare disorder and may thus be easily misdiagnosed. Misdiagnosis is even more likely when the presentation is atypical. OBJECTIVE: To present and discuss an unusual presentation of myasthenia gravis METHOD: A 67-year-old man presented with progressive ...
Background : Nemaline rod disease is a congenital myopathy, presentation of which may mimic myasthenia gravis. Methods : We report a suspected case of nemaline rod disease in a female adolescent who presented with features similar to myasthenia gravis but failed to respond effectively to its conventional management ...
Yu, S; Li, F; Chen, B; Lin, J; Yang, M; Fu, X; Li, J; Bu, B
To depict the long-term outcome of patients with myasthenia gravis after thymectomy in combination with immunotherapy, and the factors that may potentially affect the outcome. The 306 patients with myasthenia gravis who underwent extended thymectomy from January 1984 to December 2011 at Tongji Hospital were retrospectively evaluated. The patients consisted of 174 cases with thymoma and 132 cases without thymoma. Pharmaceutical treatment was tailored for each case during follow-up. Nine patients with thymomatous myasthenia gravis died during the perioperative period, and 297 patients were followed for 8.6 years. By their latest visits, 241 patients (81.1%) gained satisfactory efficacy, 24 cases died (8.1%), and 32 cases (10.8%) remained unchanged or deteriorated. Favorable factors for satisfactory efficacy included the presence of ocular myasthenia gravis before operation, no presence of thymoma, and lack of concomitant diseases. It is interesting to mention that, patients with non-thymomatous myasthenia gravis obtained significantly higher rates of complete stable remission and clinical remission than the patients with thymomatous myasthenia gravis. Extended thymectomy combined with immunotherapy is a preferred treatment with a satisfactory long-term remission rate. Patients with non-thymomatous myasthenia gravis have a much more promising prognosis than the patients with thymomatous myasthenia gravis. However, appropriate caution must be taken to discontinue pharmaceutical therapy as relapse remains a major concern after a patient who has already undergone thymectomy becomes symptom-free. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Mori, Shuuichi; Motohashi, Norio; Takashima, Rumi; Kishi, Masahiko; Nishimune, Hiroshi; Shigemoto, Kazuhiro
Since the first report of experimental animal models of myasthenia gravis (MG) with autoantibodies against low-density lipoprotein receptor-related protein 4 (LRP4), there have not been any major reports replicating the pathogenicity of anti-LRP4 antibodies (Abs). Recent clinical studies have cast doubt on the specificity and pathogenicity of anti-LRP4 antibodies for MG, highlighting the need for further research. In this study, we purified antigens corresponding to the extracellular region of human LRP4 stably expressed with chaperones in 293 cells and used these antigens to immunize female A/J mice. Immunization with LRP4 protein caused mice to develop myasthenia having similar electrophysiological and histological features as are observed in MG patients with circulating Abs against muscle-specific kinase (MuSK). Our results clearly demonstrate that active immunization of mice with LRP4 proteins causes myasthenia similar to the MG induced by anti-MuSK Abs. Further experimental and clinical studies are required to prove the pathogenicity of anti-LRP4 Abs in MG patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Myasthenia gravis (MG) is an acquired autoimmune disorder causing skeletal muscle fatigue and weakness. This is a report of one woman and her daughter presenting with myasthenia and gravis and Grave\\'s disease. It highlights possible hereditary component of this condition which has not been commonly reported in ...
Nair, Akshay Gopinathan; Patil-Chhablani, Preeti; Venkatramani, Devendra V; Gandhi, Rashmin Anilkumar
Myasthenia gravis (MG) is a disease that affects the neuro-muscular junction resulting in classical symptoms of variable muscle weakness and fatigability. It is called the great masquerader owing to its varied clinical presentations. Very often, a patient of MG may present to the ophthalmologist given that a large proportion of patients with systemic myasthenia have ocular involvement either at presentation or during the later course of the disease. The treatment of ocular MG involves both the neurologist and ophthalmologist. Thus, the aim of this review was to highlight the current diagnosis, investigations, and treatment of ocular MG. PMID:25449931
Full Text Available Netherton syndrome, a rare autosomal recessive genetic disorder, is classified as an ichthyosiform syndrome. In this report we present the case of a neonate with erythroderma shortly after birth, accompanied by severe hypernatremia, recurrent infections, transient hyperaldosteronism, and signs of growth hormone (GH deficiency. DNA molecular analysis in the SPINK5 gene revealed heterozygosity in our index patient for 238insG and 2468delA frameshift mutations in exons 4 and 26, respectively, in the maternal allele and 1431-12G>A splice-site mutation in intron 15 in the paternal allele as well as the missense variation E420K in homozygous state. Combination of the identified mutations along with transient hyperaldosteronism and possible GH deficiency have not been described before. Accordingly, the importance of early multidisciplinary approach is highlighted, in order to reach accurate diagnosis, initiate prompt treatment, and ensure survival with fewer disease complications.
Corina Ramona Nicolescu
Full Text Available Diabetes, rare in the neonatal period, should be evoked in every newborn presenting with unexplained intrauterine and early postnatal growth retardation.This case report illustrates the clinical course and therapeutic approach of a newborn diagnosed with transient diabetes. The baby was born at 37 weeks of gestation with a severe intrauterine growth restriction. Except a mild macroglossia and signs of growth restriction, physical examination was normal. On the 5th day of life hyperglycemia (180 mg/dl was noted and the next day the diagnosis of diabetes was confirmed (high blood sugar, glucosuria, undetectable levels of insulin and C-peptide. Insulin infusion, initially intravenously and then subcutaneously was started, tailored to assure the growth catch-up and normalize the blood sugar levels. At the age of 4 weeks, the baby returned at home under pump.At 8 weeks, the clinical impression of evolution to a transient diabetes (decreasing needs of insulin with very satisfactory weight gain was genetically confirmed (paternal uniparental disomy of chromosome 6.There is no screening for neonatal diabetes, but the clinical suspicion avoids the metabolic decompensation and allows early initiation of insulin therapy. The genetic approach (for disease itself and its associated features relies on timely clinical updates.
Hugh J Freeman; Helen R Gillett; Peter M Gillett; Joel Oger
Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a glutenfree diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological studies. Frozen stored serum samples from 23 acetylcholine receptor antibody positive myasthenia gravis patients with no intestinal symptoms were used to screen for celiac disease. Both endomysial and tissue transglutaminase antibodies were examined. One of 23 (or, about 4.3%) was positive for both IgA-endomysial and IgA tissue transglutaminase antibodies. Endoscopic studies subsequently showed duodenal mucosal scalloping and biopsies confirmed the histopathological changes of celiac disease. Celiac disease and myasthenia gravis may occur together more often than is currently appreciated. The presence of motor weakness in celiac disease may be a clue to occult myasthenia gravis, even in the absence of intestinal symptoms.
Barnett, Carolina; Bril, Vera; Kapral, Moira; Kulkarni, Abhaya; Davis, Aileen M
Myasthenia gravis is characterized by weakness and fatigability of different muscle groups, including ocular, bulbar and the limbs. Therefore, a measure of disease severity at the impairment level in myasthenia needs to reflect all the relevant impairments, as well as their variations with activity and fatigue. We conducted a qualitative study of patients with myasthenia, to explore their experiences and related impairments, aimed at developing a conceptual framework of disease severity at the impairment level in myasthenia gravis. Twenty patients representing the spectrum of disease participated in semi-structured interviews. Interviews were recorded and the transcripts were analyzed by content analysis using an inductive approach with line-by-line open coding. Themes were generated from these codes. Two main themes were identified: the severity of the impairments and fatigability (i.e., triggering or worsening of an impairment with activity). The impairments were further classified within body regions (ocular, bulbar and axial/limbs). Fatigability was described as a phenomenon affecting the whole body but also affecting specific impairments, and was associated with fluctuation of the symptoms. Patients were concerned that clinical examination at a single point in time might not reflect their true clinical state due to fatigability and fluctuations in severity. This conceptual framework reflects the relevance of both severity and fatigability in understanding impairment-based disease severity in myasthenia. This framework could inform the development of impairment measures in myasthenia gravis.
Full Text Available BACKGROUND: Myasthenia gravis is characterized by weakness and fatigability of different muscle groups, including ocular, bulbar and the limbs. Therefore, a measure of disease severity at the impairment level in myasthenia needs to reflect all the relevant impairments, as well as their variations with activity and fatigue. We conducted a qualitative study of patients with myasthenia, to explore their experiences and related impairments, aimed at developing a conceptual framework of disease severity at the impairment level in myasthenia gravis. METHODS: Twenty patients representing the spectrum of disease participated in semi-structured interviews. Interviews were recorded and the transcripts were analyzed by content analysis using an inductive approach with line-by-line open coding. Themes were generated from these codes. RESULTS: Two main themes were identified: the severity of the impairments and fatigability (i.e., triggering or worsening of an impairment with activity. The impairments were further classified within body regions (ocular, bulbar and axial/limbs. Fatigability was described as a phenomenon affecting the whole body but also affecting specific impairments, and was associated with fluctuation of the symptoms. Patients were concerned that clinical examination at a single point in time might not reflect their true clinical state due to fatigability and fluctuations in severity. CONCLUSIONS: This conceptual framework reflects the relevance of both severity and fatigability in understanding impairment-based disease severity in myasthenia. This framework could inform the development of impairment measures in myasthenia gravis.
Yeh, J-H; Lin, C-M; Chiu, H-C; Bai, C-H
The objective of the study was to examine predictors for sleep-disordered breathing (SDB) in patients with myasthenia gravis (MG) using Watch-PAT. We prospectively studied 58 consecutive patients with MG without respiratory symptoms for a full-night Watch-PAT with concomitant recording of the MG score and acetylcholine receptor antibody concentration and analyzed potential risk factors of SDB. Twenty-four patients (41%) had definitive SDB, which was mild in 12 patients, moderate in six, and severe in six. Assessing risk factors with multivariate models, we found four significant predictors (BMI, age, male gender, and use of azathioprine); BMI was the most powerful predictor. The severity and prevalence of sleep-disordered breathing had no significant association with MG score, myasthenia stage, or seropositivity of acetylcholine receptor antibody. The prevalence of SDB in myasthenic patients with mild and moderate weakness was high when using the Watch-PAT. Both myasthenia-specific factors (use of azathioprine) and general predictors in terms of BMI, age, and male gender predisposed the development of SDB in patients with myasthenia gravis. Careful screening of patients with myasthenia gravis at risk of SDB using Watch-PAT might improve the quality of sleep and cardiovascular health through proper treatment of underlying SDB. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Liu, Chanchan; Gui, Mengcui; Cao, Yayun; Lin, Jing; Li, Yue; Ji, Suqiong; Bu, Bitao
Myasthenia gravis tends to affect children in China. Oral pyridostigmine and prednisone could effectively improve the symptoms, but multiple side effects become a major concern after long-term oral prednisone. To avoid the long-term complications of prednisone therapy and to obtain more satisfactory improvement, we tested the efficacy and safety of tacrolimus in children with myasthenia gravis. Children with myasthenia gravis who had not achieved satisfactory improvement or who experienced severe side effects after prednisone therapy were recruited between January 2015 and December 2016 at Tongji Hospital. All the children were treated with tacrolimus 1 mg to 2 mg daily and the dose was adjusted on the basis of the clinical response and the serum concentration. The dosage of prednisone, the severity of symptoms, blood samples, the serum concentration of tacrolimus, and titers of antiacetylcholine receptor antibodies were evaluated every four weeks. Fourteen children were enrolled. One child withdrew two weeks after the enrollment. Thirteen children have completed the therapy for one year. At the end point, the dosage of prednisone was significantly decreased (P myasthenia gravis score, and myasthenia gravis-specific manual muscle testing and myasthenia gravis-activities of daily living scores were significantly improved (P myasthenia gravis. Randomized clinical trials are needed to confirm the observation. Copyright © 2017 Elsevier Inc. All rights reserved.
Full Text Available Abstract Myasthenia gravis is an autoimmune disorder that is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. Diagnosis of myasthenia gravis is made following clinical and physical examination and is confirmed by serum immunoassays to measure autoantibody levels. Myasthenia gravis especially when associated with pregnancy is a high-risk disease, and its course is unpredictable. We described the second report about use of sugammadex after rocuronium for a caesarean delivery with myasthenia gravis, but, unlike our case that formerly was diagnosed with myasthenia gravis, the patient was extubated on postoperative successfully and we did not encounter any respiratory problems.
Good nutrition is important for everyone. This is especially true when you have a chronic disorder like myasthenia gravis ( ... difficulty with chewing and swallowing may interfere with nutrition and create safety issues. Diet modifications may be ...
Sehgal, Shekhar; Rebello, Roshan; Wolmarans, Louise; Elston, Marianne
We present two patients with Graves' disease and concurrent myasthenia gravis. The impact of the dual diagnosis on the clinical course and the potential for a delayed diagnosis of myasthenia gravis is discussed. Patient 1, a 28-year-old man was diagnosed with Graves' disease following his second respiratory arrest. His history was strongly suggestive of a second pathology. Patient 2, a 66-year-old Cantonese woman with established Graves' disease presented with thionamide-related neutropaenia. Examination revealed bilateral ptosis and right lateral rectus palsy. Both patients had thyrotoxicosis secondary to Graves' disease with concurrent myasthenia gravis. Although neuromuscular weakness is common in Graves' disease, coexisting myasthenia gravis (MG) is rare and can cause profound morbidity. Ocular signs in both diseases may cause diagnostic confusion although ptosis suggests coexisting MG. In both cases, the thyrotoxicosis delayed the diagnosis of MG. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Background Since there has been no conclusive evidence regarding the treatment of ocular myasthenia, treatment guidelines were recently issued by the European Federation of Neurological Societies/European Neurological Society (EFNS/ENS). However, the therapeutic outcomes concerning the quality-of-life (QOL) of patients with ocular myasthenia are not yet fully understood. Methods We investigated the therapeutic outcomes of patients with purely ocular myasthenia in a multicenter cross-sectional survey in Japan. To evaluate the severity of ocular symptoms, we used the ocular-quantitative MG (QMG) score advocated by Myasthenia Gravis Foundation of America. We used the Japanese translated version of the MG-QOL15, a self-appraised scoring system. Results Of 607 myasthenia gravis (MG) patients with an observation-duration of illness ≥ 2 years, the cases of 123 patients (20%) were limited to ocular muscles (purely ocular myasthenia). During the entire clinical course, 81 patients experienced both ptosis and diplopia, 36 had ptosis alone, and six had diplopia alone. Acetyl-cholinesterase inhibitors and prednisolone were used in 98 and 52 patients, respectively. Treatment improved ocular symptoms, with the mean reduction in ocular-QMG score of 2.3 ± 1.8 points. However, 47 patients (38%) failed to gain minimal manifestation or a better status. Patients with unfavorable outcomes also self-reported severe QOL impairment. Multivariate analyses showed that the pretreatment ocular-QMG score was associated with unfavorable outcomes, but not associated with the patient’s QOL. Conclusion A treatment strategy designed in accord with a patient's ocular presentation must be considered in order to improve ocular symptoms and the patient's QOL. PMID:24996227
Suzuki, Masayuki; Takashima, Tsutomu; Itoh, Hiroshi
In this report, preoperative CT diagnosis of the thymus was reevaluated in 15 operated patients with myasthenia gravis. Using GE CT/T 8800 wholebody scanner, pre- and/or post-contrast study was performed from the apex to the diaphragm level. Five cases of thymoma, 5 out of 6 cases of thymic hyperplasia and 3 cases of normal thymus were correctly diagnosed. One hyperplasia was diagnosed as normal and one normal thymus as hyperplasia. At the CT evaluation of the thymus in patients with myasthenia gravis, it is easy to detect thymoma, but it is often difficult to differentiate thymic hyperplasia and normal thymus due to the aging changes in the gland and the presence of localized hyperplasia. (author)
Soyoral, Lokman; Goktas, Ugur; Cegin, Muhammed Bilal; Baydi, Volkan
Myasthenia gravis is an autoimmune disorder that is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. Diagnosis of myasthenia gravis is made following clinical and physical examination and is confirmed by serum immunoassays to measure autoantibody levels. Myasthenia gravis especially when associated with pregnancy is a high-risk disease, and its course is unpredictable. We described the second report about use of sugammadex after rocuronium for a caesarean delivery with myasthenia gravis, but, unlike our case that formerly was diagnosed with myasthenia gravis, the patient was extubated on postoperative successfully and we did not encounter any respiratory problems. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.
Soyoral, Lokman; Goktas, Ugur; Cegin, Muhammed Bilal; Baydi, Volkan
Myasthenia gravis is an autoimmune disorder that is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. Diagnosis of myasthenia gravis is made following clinical and physical examination and is confirmed by serum immunoassays to measure autoantibody levels. Myasthenia gravis especially when associated with pregnancy is a high-risk disease, and its course is unpredictable. We described the second report about use of sugammadex after rocuronium for a caesarean delivery with myasthenia gravis, but, unlike our case that formerly was diagnosed with myasthenia gravis, the patient was extubated on postoperative successfully and we did not encounter any respiratory problems. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.
Hargreave, Marie; Kjaer, Susanne Krüger; Jørgensen, Marit Eika
AIMS: The study of imprinting disorders in the context of infertility and its treatment is important, as studies have indicated an increased risk. In this study, we evaluated the risk of transient neonatal diabetes mellitus (TNDM), defined here as diabetes mellitus presenting within the first six...... for TNDM, after adjustment for birth year, maternal age at birth and parental history of diabetes, although this was not statistically significant (HR = 1.49; 95% CI 0.73-3.03). The risk of children born in the period 1994-2010 (a period with more comprehensive information on maternal fertility problems...... and with more invasive fertility treatment procedures) was increased almost twofold (HR = 1.92; 95% CI 0.92-4.00) but was still not statistically significant. CONCLUSIONS: Our results indicate that children born to women with fertility problems, particularly after 1993, may be at an elevated risk for TNDM...
Ko, Eun Sook; Jeon, Kyung Nyeo; Bae, Kyung Soo; Yoo, Jin Jong; Kang, Duk Sik
A thymoma often occurs in patients with myasthenia gravis, but the development of multiple thymoma is very rare. The authors report the radiologic and pathologic findings of multiple invasive thymoma in a 59-year-old male with myasthenia gravis
Ko, Eun Sook; Jeon, Kyung Nyeo; Bae, Kyung Soo; Yoo, Jin Jong [College of Medicine, Gyeongsang National Univ., Jinju (Korea, Republic of); Kang, Duk Sik [College of Medicine, Kyungpook National Univ., Daegu (Korea, Republic of)
A thymoma often occurs in patients with myasthenia gravis, but the development of multiple thymoma is very rare. The authors report the radiologic and pathologic findings of multiple invasive thymoma in a 59-year-old male with myasthenia gravis.
Alam, Md. Shahid
Full Text Available Myasthenia gravis is an autoimmune disorder affecting the neuromuscular junction. Ocular myasthenia gravis presents as ptosis with extraocular motility restriction and is prone to be misdiagnosed as third nerve palsy or congenital or aponeurotic ptosis. Juvenile ocular myasthenia gravis in very young children is difficult to diagnose and can be easily labeled as a case of congenital ptosis, the more so when the condition is bilateral. We present a case of a two-year-old child who presented with bilateral ptosis and was diagnosed as a case of simple congenital ptosis elsewhere with the advice to undergo tarsofrontalis sling surgery. The child was diagnosed with juvenile myasthenia gravis on thorough history, examination, and systemic evaluation and was started on anti-myasthenic treatment.
Meriggioli, Matthew N; Sanders, Donald B
Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. A number of molecules, including ion channels and other proteins at the neuromuscular junction, may be targeted by autoantibodies leading to abnormal neuromuscular transmission. In approximately 85% of patients, autoantibodies, directed against the postsynaptic nicotinic acetylcholine receptor can be detected in the serum and confirm the diagnosis, but in general, do not precisely predict the degree of weakness or response to therapy. Antibodies to the muscle-specific tyrosine kinase are detected in approximately 50% of generalized myasthenia gravis patients who are seronegative for anti-acetylcholine receptor antibodies, and levels of anti-muscle-specific tyrosine kinase antibodies do appear to correlate with disease severity and treatment response. Antibodies to other muscle antigens may be found in the subsets of myasthenia gravis patients, potentially providing clinically useful diagnostic information, but their utility as relevant biomarkers (measures of disease state or response to treatment) is currently unclear. PMID:22882218
Barnett, Carolina; Bril, Vera; Kapral, Moira; Kulkarni, Abhaya V; Davis, Aileen M
To study responsiveness and meaningful change of the Myasthenia Gravis Impairment Index (MGII) and its relative efficiency compared to other measures. We enrolled 95 patients receiving prednisone, IV immunoglobulin (IVIg), or plasma exchange (PLEX) and 54 controls. Patients were assessed with the MGII and other measures-including the Quantitative Myasthenia Gravis Score, Myasthenia Gravis Composite, and Myasthenia Gravis Activities of Daily Living-at baseline and 3-4 weeks after treatment. Statistical markers of responsiveness included between-groups and within-group differences, and we estimated the relative efficiency of the MGII compared to other measures. Patient-meaningful change was assessed with an anchor-based method, using the patient's impression of change. We determined the minimal detectable change (MDC) and the minimal important difference (MID) at the group and individual level. Treated patients had a higher change in MGII scores than controls (analysis of covariance p 1 favoring the MGII. The MGII demonstrated responsiveness to prednisone, IVIg, and PLEX in patients with myasthenia. There is a differential response in ocular and generalized symptoms to type of therapy. The MGII has higher relative efficiency than comparison measures and is viable for use in clinical trials. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
Almeida, Carlos; Coutinho, Ester; Moreira, Daniela; Santos, Ernestina; Aguiar, José
Myasthenia gravis is an autoimmune neuromuscular disease, usually affecting women in the second and third decades. The course is unpredictable during pregnancy and puerperium. Myasthenia gravis can cause major interference in labour and partum and exacerbations of the disease frequently occur. The aim of this series of cases is to analyse retrospectively the anaesthetic management of myasthenia gravis patients and complications during the peripartum period. Retrospective, single centre study from clinical files of female myasthenia gravis patients who delivered between 1985 and 2007 at Hospital de Santo António, Porto, Portugal. Seventeen myasthenia gravis patients delivered between 1985 and 2007 in Hospital Santo António. Two women were not included in the study as they had a spontaneous abortion in the first trimester. Four patients presented exacerbations of the disease during pregnancy, no exacerbation occurred in eight patients and three patients presented their first symptoms of myasthenia gravis during pregnancy (without diagnosis at time of delivery). Concerning the eight patients without exacerbations of the disease during pregnancy, pregnancy was brought to term in 87.5% of the cases; five women were submitted to nonurgent caesarean section (62.5%); and epidural block was performed in six patients (75%). No complications related to anaesthesia occurred in the peripartum period. Concerning the four patients with exacerbations of the disease, pregnancy was brought to term in three cases (75%); three women were submitted to nonurgent caesarean section (75%); and epidural block was performed in three patients (75%). One patient underwent an uncomplicated thymectomy under general anaesthesia during pregnancy and, in the postpartum period, there was a myasthenic crisis in another patient. Concerning the three patients without a myasthenia gravis diagnosis at partum, one woman already being followed for presenting muscular weakness had a vaginal delivery under
Vázquez-Roque, F J; Hernández-Oliver, M O; Medrano Plana, Y; Castillo Vitlloch, A; Fuentes Herrera, L; Rivero-Valerón, D
Radical or extended thymectomy is an effective treatment for myasthenia gravis in the adult population. There are few reports to demonstrate the effectiveness of this treatment in patients with juvenile myasthenia gravis. The main objective of this study was to show that extended transsternal thymectomy is a valid option for treating this disease in paediatric patients. Twenty-three patients with juvenile myasthenia gravis underwent this surgical treatment in the period between April 2003 and April 2014; mean age was 12.13 years and the sample was predominantly female. The main indication for surgery, in 22 patients, was the generalised form of the disease (Osserman stage II) together with no response to 6 months of medical treatment. The histological diagnosis was thymic hyperplasia in 22 patients and thymoma in one patient. There were no deaths and no major complications in the postoperative period. After a mean follow-up period of 58.87 months, 22 patients are taking no medication or need less medication to manage myasthenic symptoms. Extended (radical) transsternal thymectomy is a safe and effective surgical treatment for juvenile myasthenia gravis. Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Manoj K Sanwal
Full Text Available Myasthenia Gravis (MG is an acquired, autoimmune disorder affecting neuromuscular junction presenting with easy fatigability, progressive weakness, diplopia, difficulty in speaking and swallowing and even ventilatory failure in severe cases. During pregnancy the disease may go into remission or may exacerbate at any time during first, second and third trimesters or postpartum period. We are reporting the case of a 28 year old primigravida, known case of MG, who underwent caesarean section and developed muscular weakness on third postoperative day. Her neonate also had tachypnoea and hypotonia, Both, the mother and the baby were managed aggressively and responded well to therapy.
Eizaguirre, María Bárbara; Aguirre, Florencia; Yastremiz, Cecilia; Vanotti, Sandra; Villa, Andrés
Myasthenia gravis is a chronic autoimmune disease that affects the neuromuscular transmission. Controversial findings had been reported about cognitive impairment in this disease. The aim of this study was to investigate the cognitive pattern of patients with myasthenia gravis. There were enrolled 24 patients with myasthenia gravis, anti-acetylcholine receptor antibodies (ACRA) positive, and 24 healthy controls. age 43.9 ± 14.8, years of education 10.9 ± 3.3. age 44.5 ± 15.4, years of education 11.5 ± 3.3. The following areas were evaluated: verbal memory: (long-term storage, retrieval, delayed recall) of the Selective Remained Test; attention: Paced Auditory Serial Addition Task (PASAT 2 and 3 seconds); executive functions: analogies and numbers-letters sequence. Also, it was administered the Beck Depression Inventory II (BDI II). About 33.3% of patients obtained abnormal performance in two or more cognitive tests. 37.5% showed deterioration in attention; 33.3% in verbal memory; 29.2% in executive functions. Significant differences between patients and healthy controls were found in long-term storage (p = 0.001); retrieval (p = 0.007); delayed recall (p = 0.000); PASAT 3 (p = 0.009); PASAT 2 (p = 0.009) and analogies (p = 0.003). Evidence of depression was found: mild in 4.2% of patients; moderate in 25% and severe in 29.2%. Neuropsychological performance declines in patients with myasthenia gravis: attention was more affected than other cognitive areas.
Kim, Guk Hee [Insung Hospital, Chuncheon (Korea, Republic of); Kang, Eun Young; Lee, Nam Joon; Suh, Won Hyuck [Korea University College of Medicine, Seoul (Korea, Republic of)
The relationship between myasthenia gravis and the thymus was well establish and myasthenia gravis occurs in the presence of thymic hyperplasia or thymoma or occasionally in histologically normal thymus. Since not every patients with myasthenia gravis is a candidate for thymectomy, unless a thymoma is present, the differentiation of normal and hyperplastic thymus from thymoma becomes important. Authors reviewed retrospectively clinical records and chest CT scans of 18 patients with myasthenia gravis who underwent thymectomy during recent 5 years, to evaluate the role of CT scan. The results were as follows. 1 Of total 18 cases, 5 cases had normal thymus, 6 cases had thymic hyperplasia, 4 cases had benign thymoma and 3 cases had malignant thymoma. 2. Of 5 cases of normal thymus, no false positive cases were noted in CT scan. 3. Of 6 cases of thymic hyperplasia, CT findings were normal except 1 cases of thickened left thymic lobe. 4. Of 7 cases of thymoma, no false negative cases were noted in CT scan. 5. CT findings of benign thymoma were round or oval shaped, discrete, slightly enhancing soft tissue mass in anterior mediastinum. 6. CT findings of malignant thymoma were lobulated contoured, infiltrative, soft tissue mass lesion in anterior mediastinum with calcifications, pleural tumor implants, and SVC compression. CT yielded valuable information on differential diagnosis of thymoma, thymic hyperplasia and normal thymus. Also CT was a highly sensitive method in the detection of thymoma and determining the extent and invasiveness.
Kim, Guk Hee; Kang, Eun Young; Lee, Nam Joon; Suh, Won Hyuck
The relationship between myasthenia gravis and the thymus was well establish and myasthenia gravis occurs in the presence of thymic hyperplasia or thymoma or occasionally in histologically normal thymus. Since not every patients with myasthenia gravis is a candidate for thymectomy, unless a thymoma is present, the differentiation of normal and hyperplastic thymus from thymoma becomes important. Authors reviewed retrospectively clinical records and chest CT scans of 18 patients with myasthenia gravis who underwent thymectomy during recent 5 years, to evaluate the role of CT scan. The results were as follows. 1 Of total 18 cases, 5 cases had normal thymus, 6 cases had thymic hyperplasia, 4 cases had benign thymoma and 3 cases had malignant thymoma. 2. Of 5 cases of normal thymus, no false positive cases were noted in CT scan. 3. Of 6 cases of thymic hyperplasia, CT findings were normal except 1 cases of thickened left thymic lobe. 4. Of 7 cases of thymoma, no false negative cases were noted in CT scan. 5. CT findings of benign thymoma were round or oval shaped, discrete, slightly enhancing soft tissue mass in anterior mediastinum. 6. CT findings of malignant thymoma were lobulated contoured, infiltrative, soft tissue mass lesion in anterior mediastinum with calcifications, pleural tumor implants, and SVC compression. CT yielded valuable information on differential diagnosis of thymoma, thymic hyperplasia and normal thymus. Also CT was a highly sensitive method in the detection of thymoma and determining the extent and invasiveness
María Bárbara Eizaguirre
Full Text Available Myasthenia gravis is a chronic autoimmune disease that affects the neuromuscular transmission. Controversial findings had been reported about cognitive impairment in this disease. The aim of this study was to investigate the cognitive pattern of patients with myasthenia gravis. There were enrolled 24 patients with myasthenia gravis, anti-acetylcholine receptor antibodies (ACRA positive, and 24 healthy controls. Patients: age 43.9 ± 14.8, years of education 10.9 ± 3.3. Controls: age 44.5 ± 15.4, years of education 11.5 ± 3.3. The following areas were evaluated: verbal memory: (long-term storage, retrieval, delayed recall of the Selective Remained Test; attention: Paced Auditory Serial Addition Task (PASAT 2 and 3 seconds; executive functions: analogies and numbers-letters sequence. Also, it was administered the Beck Depression Inventory II (BDI II. About 33.3% of patients obtained abnormal performance in two or more cognitive tests. 37.5% showed deterioration in attention; 33.3% in verbal memory; 29.2% in executive functions. Significant differences between patients and healthy controls were found in long-term storage (p = 0.001; retrieval (p = 0.007; delayed recall (p = 0.000; PASAT 3 (p = 0.009; PASAT 2 (p = 0.009 and analogies (p = 0.003. Evidence of depression was found: mild in 4.2% of patients; moderate in 25% and severe in 29.2%. Neuropsychological performance declines in patients with myasthenia gravis: attention was more affected than other cognitive areas
Aragonès, J M; Altimiras, J; Roura, P; Alonso, F; Bufill, E; Munmany, A; Alfonso, S; Illa, I
The reported prevalence of myasthenia gravis ranges between 5 and 24 cases per 100,000, and people over 65years account for less than 50% of all cases. The prevalence and clinical characteristics of myasthenia gravis in the county of Osona were studied in patients younger and older than 65. The study draws from the county-based prospective myasthenia gravis register implemented by the Neurology Department at Hospital General de Vic in 1991. The prevalence of myasthenia gravis was 32.89×10 5 inhabitants (95%CI, 23.86-41.91). The standardized prevalence (European population) was 35.47×10 5 inhabitants (95%CI, 26.10-44.84). The ratio of women to men was 1.3. Overall, the group of patients older than 65 accounted for 62.75% of all cases. The prevalence of myasthenia gravis increased considerably in older age groups. No cases were registered among patients under 25years old, prevalence was 21.87×10 5 in the 25 to 64 age group, and prevalence in patients over 65 years increased to 122.35×10 5 . The clinical characteristics prior to treatment and at the cut-off date are similar (P>.05) in patients younger than 65 and those aged 65 and older. These figures show the highest prevalence rate reported to date. This high prevalence is due to the rate observed among patients older than 65. These results provide a new warning that myasthenia gravis may be underdiagnosed in the elderly population. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.
Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E. [Haukeland Sykehus, Bergen (Norway)
The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs.
Martínez Torre, S; Gómez Molinero, I; Martínez Girón, R
Myasthenia gravis is one of the most common disorders that affect neuromuscular transmission. It is currently one of the most understood and characterised autoimmune disorders Its typical symptoms are fluctuating weakness and fatigue that affects a combination of ocular muscles, bulbar functions, as well as limb and respiratory muscles, which are due to an immune attack against the postsynaptic membrane of the neuromuscular junction. The diagnosis of myasthenia gravis is based on clinical and serological test. It is a disease that can be effectively controlled with the current therapeutic lines, even achieving a complete remission. An update of this interesting disorder is now presented. Copyright © 2018 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.
Motobayashi, Mitsuo; Inaba, Yuji; Nishimura, Takafumi; Kobayashi, Norimoto; Nakazawa, Yozo; Koike, Kenichi
Myasthenia gravis is a B cell-mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell-activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell-activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. Serum B cell-activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell-activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell-activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. Circulating B cell-activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis. Copyright © 2015 Elsevier Inc. All rights reserved.
Croitoru Cristina Georgiana
Full Text Available Myasthenia gravis is one of the neurological diseases with a relatively recent history, full of mistakes, in which the British and German neurology schools have attempted to find answers when confronted with the unknown. The paper aims at making a historical account of the disease from its discovery in the 16th century, when the first case of myasthenia gravis was medically diagnosed, to the beginning of the 20th century, when the dawn of modern therapy started to show.
Erkan Turan, Kadriye; Kocabeyoglu, Sibel; Bekircan-Kurt, Can Ebru; Bezci, Figen; Erdem-Ozdamar, Sevim; Irkec, Murat
To evaluate ocular surface alterations and characteristics of corneal basal epithelium and subbasal nerves in patients with myasthenia gravis. Myasthenia gravis patients (n = 21) and healthy controls (n = 20) were enrolled. All participants underwent ocular surface testing in the following order: tear break-up time, lissamine green staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index questionnaire. The Cochet-Bonnet esthesiometer was used to measure corneal sensitivity. Basal epithelial cells and subbasal nerves were evaluated using in vivo confocal microscopy. Myasthenia gravis patients had higher Ocular Surface Disease Index score (13.9 ± 15.0 vs 1.4 ± 2.2, p myasthenia gravis had lower basal epithelial cell density (3775.7 ± 938.1 vs 4983.1 ± 608.5, p myasthenia gravis and the number of corneal nerves (rho = -0.497, p = 0.022). Significant alterations of basal epithelial cells and subbasal nerves were demonstrated in myasthenia gravis patients although there was no difference of corneal sensitivity between myasthenia gravis patients and healthy controls. Thus, it should be borne in mind that myasthenia gravis patients deserve further evaluation with regard to ocular surface disease.
Koopman, Wilma J; LeBlanc, Nicole; Fowler, Sue; Nicolle, Michael W; Hulley, Denise
Myasthenia gravis significantly impacts quality of life. However, the relationship between hope, coping, and quality of life (QOL)in myasthenia patients has not been studied (Kulkantrakorn & Jarungkiatkul, 2009; Raggi et al., 2010). The aim of this study was to explore the relationship between hope, coping, and quality of life in adults with myasthenia gravis. Subjects with MG (n = 100) completed six questionnaires, including a demographic profile, the Myasthenia Gravis Activities of Daily Living Scale (MG-ADL), Herth Hope Index (HHI), Jalowiec Coping Scale (JCS), Myasthenia Gravis Quality-of-Life Scale (MG-QOL15), and Short Form Health Survey (SF-36v2). Mean hope scores indicated a high level of hope. An optimistic coping style was the most common and effective coping strategy identified by subjects. Positive thinking and humour were also frequently used strategies. Participants identified quality of life as good tolerability, above general population mental well-being, and below general populationphysical well-being. Participants who identified good quality of life had low scores on the MG-QOL15 scale and high scores on the SF36v2. Hope and independence for activities of daily living were found to correlate with improved quality of life and mental well-being(p life in the relationship between hope and coping. Hope and coping were not important factors for well-being or quality of life. Nurses caring for adults with myasthenia gravis should use interventions that continue to support hope, quality of life, and coping throughout the unpredictable and chronic course of MG.
Lee, John-Ih; Jander, Sebastian
Myasthenia gravis is the most frequent acquired disorder of neuromuscular transmission. In the majority of cases, pathogenic antibodies against components of the postsynaptic muscle endplate membrane can be detected. In recent years there have been significant advances in the pathophysiological understanding and therapy of the disease. Areas covered: PubMed searches were conducted for the term 'myasthenia gravis' cross-referenced with the terms 'immunology', 'subgroups', 'antibody', 'ocular', 'thymoma', 'treatment' and 'thymectomy'. Additionally, we summarized the current state of immunopathology and therapy. Expert commentary: Immunological research defined new target antigens at the postsynaptic neuromuscular junction which along with clinical features allow a refined definition of disease subgroups. Overall the prognosis of myasthenia gravis with best possible symptomatic, immunosuppressive and supportive treatment is good but new immunomodulatory treatment options are developed for patients who do not respond well to the first line therapy. For most patients individually adapted long-term drug therapy is needed.
Helgeland, G.; Petzold, A.F.S.; Luckman, S.P.; Gilhus, N.E.; Plant, G.T.; Romi, F.R.
Introduction: Myasthenia gravis (MG) is an autoimmune disease with weakness in striated musculature due to anti-acetylcholine receptor (AChR) antibodies or muscle specific kinase at the neuromuscular junction. A subgroup of patients has periocular symptoms only; ocular MG (OMG). Matrix
Zeitlhofer, J.; Maida, E.M.; Mamoli, B.; Mayr, N.
In a retrospective study in 47 patients with myasthenia gravis acetylcholine-receptor-antibody-titers (AChR-AB) were correlated with the severity of the disease. In 18 patients the course of titers was studied and two groups of patients could be differentiated: patients with relative constant and patients with fluctuating titers. Age, age of begin of myasthenia and sex did not influence the titers. Also the duration of the disease and the severity of symptoms did not influence the level of AChR-AB-titers. In this retrospective study the influence of immunsuppressive therapy on the intra-individual course of AB-titers and their correlation with the clinical symptoms could not be judged. Measurement of AChR-AB is of value for the diagnosis of myasthenia gravis and important for judging the clinical course and the effect of therapy. (Author)
Bagheri, Reza; Boonstani, Reza; Sadrizadeh, Ali; Salehi, Maryam; Afghani, Reza; Rahnama, Ali; Azmounfar, Vahab; Hakimian, Saeed; Baradaran Firoozabadi, Mohammad
Thymectomy considered as a standard procedure in treatment of all the steps of myasthenia gravis. Video-assisted thoracoscopic surgery (VATS) thymectomy is one of the minimally invasive procedures that because of the short duration of hospitalization, less postoperative pain, and scar after surgery, nowadays it is replaced the traditional methods of surgery for patients with myasthenia gravis, but there are still differences and concerns. The aim of this study was to compare outcomes of two different techniques of surgery, VATS versus transsternal (TS) in the treatment of myasthenia gravis. In this pilot study, 42 patients with myasthenia gravis and without a thymus tumor were evaluated based on Myasthenia Gravis Foundation of America classification and drug consumption. Then, they randomly underwent two different techniques of surgery: VATS versus TS. Patients were evaluated based on preoperative and postoperative variables. Duration of intensive care unit stay and hospitalization has been reduced in patients who underwent VATS thymectomy operation technique. In addition, duration of surgical procedure has been reduced significantly in these patients. These patients have less blood loss during surgery compared with TS group. The Myasthenia Gravis Foundation of America postoperative status in VATS thymectomy revealed that the number of patients with complete stable remission was higher and number of persons remained unchanged was lower in this group. VATS thymectomy is a safe and appropriate approach comparing with traditional methods such as TS thymectomy for patients with myasthenia gravis. This method has better results after surgery and can be used as a minimally invasive alternative method instead of TS thymectomy.
Full Text Available Objective. To present a case of maternal myasthenia gravis in pregnancy and give a systematic review of the literature. Case. We report the case of a 38-year-old parturient with a life-threatening complication of immune-mediated myasthenia gravis shortly after an elective cesarean section on patient's request under spinal anesthesia at 35 + 3 weeks of gestation. The newborn was transferred to the pediatric unit for surveillance and did not show any signs of muscular weakness in the course of time. The mother developed a respiratory insufficiency on the second day postpartum. The myasthenic crisis led to a progressive dyspnoea within minutes, which exacerbated in a secondary generalized seizure with cardiac-circulatory arrest. After successful cardiopulmonary resuscitation, the patient was transferred to intensive care. The interdisciplinary therapeutic approach included ventilatory assistance via endotracheal intubation, parenteral pyridostigmine, azathioprine, and steroids. By interdisciplinary measures, a stable state was regained. Conclusion. Myasthenia gravis especially when associated with pregnancy is a high-risk disease. As this disease predominantly occurs in women of reproductive age, it is important to be aware of this condition in obstetrics and its interdisciplinary diagnostic and therapeutic management.
Idiaquez, J F; Gonzalez, S; Lasso-Penafiel, J; Barnett, C
Medication adherence is a public health problem and this has not been previously studied in myasthenia gravis patients. To determine if patients with myasthenia gravis are adherent to treatment and to describe the clinical factors of patients who are non-adherent to treatment. Cross-sectional study of patients with myasthenia gravis followed at Padre Hurtado Hospital, Santiago de Chile, who received their medication through the hospital and therefore were on the pharmacy's list. Patients' participation was voluntary and anonymous. Medication adherence was assessed with the Morisky-Green-Levine survey (4 items). Patients were assessed for myasthenia gravis severity with the Manual Muscle Test, and myasthenia gravis-related quality of life with the MG-QOL15. Finally, patients were screened for depression with the 12-Item General Health Questionnaire. 26 patients were enrolled and 15 (57.7%) were women. Only 10 (38.5%) of patients were adherent to treatment. Patients who were not adherent to medication had more weakness (p = 0.06), worse quality of life (p = 0.008), were taking a greater number of myasthenia gravis drugs (p = 0.003) and had a higher risk of depression (p = 0.03). In this cohort of myasthenia gravis patients, three out of five patients were not adherent to treatment. These patients tended to have more weakness, worse quality of life and higher risk of depression. Medication adherence should be assessed routinely in patients with myasthenia gravis.
Cejvanovic, S; Vissing, J
OBJECTIVE: Myasthenia gravis (MG) is characterized by fatigue and fluctuating muscle weakness as a result of impaired neuromuscular transmission (NMT). Although MG is a prototypic fatiguing disorder, little is known about how the condition affects fixed weakness, and if present, whether weakness...
Rahbek, Martin Amadeus; Mikkelsen, Erik Elgaard; Overgaard, Kristian
Introduction: It has not been established whether progressive resistance training (PRT) and aerobic training (AT) are feasible and efficient in myasthenia gravis (MG). Methods: Fifteen subjects with generalized MG (Myasthenia Gravis Foundation of America (MGFA) clinical classification II-IV) were...... randomly assigned to 20 training sessions during 8 weeks of either PRT or AT. Feasibility was evaluated based on adherence, drop-out rate, adverse events, and Quantitative Myasthenia Gravis (QMG) score. Results: Twelve subjects (MGFA II, n = 11; MGFA III, n=1) completed the intervention with a mean...
Mineo, Tommaso Claudio; Tamburrini, Alessandro; Schillaci, Orazio; Ambrogi, Vincenzo
Patients with thymoma and without clinical or electromyographical myasthenic signs may occasionally develop myasthenia several years after thymectomy. Hereby, we investigated the predictors and the evolution of this peculiar disease. We performed a retrospective analysis in 104 consecutive patients who underwent thymectomy between 1987 and 2013 for thymoma without clinical or electromyographic signs of myasthenia gravis. Predictors of post-thymectomy onset of myasthenia gravis were investigated with univariate time-to-disease analysis. Evolution of myasthenia was analyzed with time-to-regression analysis. Eight patients developed late myasthenia gravis after a median period of 33 months from thymectomy. No significant correlation was found for age, gender, Masaoka's stage, and World Health Organization histology. Only high preoperative serum acetylcholine-receptor antibodies titer (>0.3 nmol/L) was significantly associated with post-thymectomy myasthenia gravis at univariate time-to-disease (P = 0.003) analysis. Positron emission tomography was always performed in high-titer patients, and increased metabolic activity was detected in 4 of these patients. Surgical treatment through redo-sternotomy or video-assisted thoracoscopy was performed in these last cases with a remission in all patients after 12, 24, 32 and 48 months, respectively. No patient under medical treatment has yet developed a complete remission. In our study the presence of preoperative high-level serum acetylcholine receptor antibodies was the only factor significantly associated with the development of post-thymectomy myasthenia gravis. The persistence of residual islet of ectopic thymic tissue was one of the causes of the onset of myasthenia and its surgical removal was successful. Copyright © 2018 Elsevier Inc. All rights reserved.
Peeler, Crandall E; De Lott, Lindsey B; Nagia, Lina; Lemos, Joao; Eggenberger, Eric R; Cornblath, Wayne T
The sensitivity of acetylcholine receptor (AChR) antibody testing is thought to be lower in ocular myasthenia gravis (OMG) compared with generalized disease, although estimates in small-scale studies vary. There is little information in the literature about the implications of AChR antibody levels and progression from OMG to generalized myasthenia gravis. To test the hypothesis that serum AChR antibody testing is more sensitive in OMG than previously reported and to examine the association between AChR antibody levels and progression from OMG to generalized myasthenia gravis. A retrospective, observational cohort study was conducted of 223 patients (mean [SD] age, 59.2 [16.4] years; 139 [62.3%] male) diagnosed with OMG between July 1, 1986, and May 31, 2013, at 2 large, academic medical centers. Baseline characteristics, OMG symptoms, results of AChR antibody testing, and progression time to generalized myasthenia gravis (if this occurred) were recorded for each patient. Multiple logistic regression was used to measure the association between all clinical variables and antibody result. Kaplan-Meier survival analysis was performed to examine time to generalization. Among the 223 participants, AChR antibody testing results were positive in 158 participants (70.9%). In an adjusted model, increased age at diagnosis (odds ratio [OR], 1.03; 95% CI, 1.01-1.04; P = .007) and progression to generalized myasthenia gravis (OR, 2.92; 95% CI, 1.18-7.26; P = .02) were significantly associated with positive antibody test results. Women were less likely to have a positive antibody test result (OR, 0.36; 95% CI, 0.19-0.68; P = .002). Patients who developed symptoms of generalized myasthenia gravis had a significantly higher mean (SD) antibody level than those who did not develop symptoms of generalized myasthenia gravis (12.7 [16.5] nmol/L vs 4.2 [7.9] nmol/L; P = .002). We demonstrate a higher sensitivity of AChR antibody testing than previously reported in the
Full Text Available About 5-10% of patients with myasthenia gravis concomitantly have other autoimmune diseases. However, the coexistence of myasthenia gravis and pernicious anemia is rare. Here, we report a 73-year-old Taiwanese woman who developed myasthenia gravis 5 months after the onset of pernicious anemia. Her myasthenic and pernicious anemia symptoms markedly improved after pyridostigmine, prednisolone and hydroxo-cobalamine treatment. It is important to recognize concurrence of myasthenia gravis and pernicious anemia in the same patient because the therapeutic results for both diseases are rewarding.
Pedersen, E G; Pottegård, A; Hallas, J
The association between use of azathioprine and risk of non-melanoma skin cancer (NMSC) in patients with myasthenia was evaluated in a nationwide setting. Treatment of autoimmune myasthenia frequently involves long-term exposure to immunosuppressants, including azathioprine. Use of azathioprine...
Yang, Jing; Liu, Chanchan; Li, Tao; Li, Chengyan
To compare the post-thymectomy prognosis in different conditions of myasthenia gravis (MG) patients with thymus hyperplasia. Collecting medical record and carrying out the follow-up study of 123 myasthenia gravis patients with thymus hyperplasia who have underwent thymectomy during the period between 2003 and 2013. Dividing into different groups based on gender, age of onset, duration of disease and Myasthenia Gravis Association of America (MGFA) clinical classification to analyze different prognosis in different groups. Complete stable remission (CSR) was achieved in 71 of 123 patients (59.5%). There is no gender-related difference in achieving CSR. Patients with early onset of MG (≤40 years old) or disease duration less than 12 months had significantly higher CSR rates than those with late onset of MG (>40 years old) or disease duration more than 12 months respectively, while no difference was found in remission rate between MGFA clinical classification I and MGFA II. Myasthenia gravis patients with thymus hyperplasia who had thymectomy are proved to possess greater chance of achieving CSR. The onset age of disease and duration are the prognostic factors.
Shah, Poornima A; Wadia, Pettarusp Murzban
Man-in-the-barrel syndrome (MBS) is an uncommon presentation due to bilateral, predominantly proximal muscle weakness that has not been described to be associated with myasthenia gravis. We describe a case of myasthenia gravis presenting as MBS. Additionally, he had significant wasting of the deltoids bilaterally with fibrillations on electromyography (EMG) at rest and brief duration (3-6 ms) bi/triphasic motor unit potentials (MUPs) on submaximal effort apart from a decremental response on r...
Qi, Guoyan; Liu, Peng; Gu, Shanshan; Yang, Hongxia; Dong, Huimin; Xue, Yinping
Our study is aimed to explore the underlying genetic basis of myasthenia gravis. We collected a Chinese pedigree with myasthenia gravis, and whole-exome sequencing was performed on the two affected siblings and their parents. The candidate pathogenic gene was identified by bioinformatics filtering, which was further verified by Sanger sequencing. The homozygous mutation c.G40A (p.V14M) in interferon gamma receptor 1was identified. Moreover, the mutation was also detected in 3 cases of 44 sporadic myasthenia gravis patients. The p.V14M substitution in interferon gamma receptor 1 may affect the signal peptide function and the translocation on cell membrane, which could disrupt the binding of the ligand of interferon gamma and antibody production, contributing to myasthenia gravis susceptibility. We discovered that a rare variant c.G40A in interferon gamma receptor 1 potentially contributes to the myasthenia gravis pathogenesis. Further functional studies are needed to confirm the effect of the interferon gamma receptor 1 on the myasthenia gravis phenotype.
Kisabay, Aysin; Sari, Ummu Serpil; Boyaci, Recep; Batum, Melike; Yilmaz, Hikmet; Selcuki, Deniz
Myasthenia gravis is a disease of neuromuscular junction due to auto-immune destruction of the acetylcholine receptors. Behçet's disease, on the other hand, is a multisystemic vascular-inflammatory disease. Both conditions are not common in the general population although their association has not been reported in the literature. We wanted to present our patient who developed clinical course of myasthenia gravis following discontinuation of medications due to complications of corticosteroid for Behçet's disease. It was observed that clinical findings of myasthenia gravis recovered following restarting steroid treatment and he did not experience attacks of both conditions. Although Myasthenia gravis and Behçet's disease are distinct entities clinically as well as in terms of pathogenesis, they share common physiopathological features and their treatment is based on their common features. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
Myasthenia gravis, a rare disorder of the neuromuscular transmission, is increasingly acknowledged as a syndrome more than as a single disease. This review summarizes recent advances in pathophysiology which confirm the disease heterogeneity, and may help find disease-targeted and patient-targeted therapies. Antibodies to the acetylcholine receptor, the muscle-specific tyrosine kinase and the lipoprotein receptor protein 4, characterize disease subtypes with distinct clinical traits and immune-pathogenic mechanisms. Genome-wide approaches have identified susceptibility loci within genes that participate in the immune response. Regulatory T and B cells appear to be defective in myasthenia gravis. In patients with acetylcholine receptor antibodies, thymectomy associated with prednisone proved more effective than prednisone alone in a multicenter randomized trial. New therapeutic options target B cells, B-cell growth factors and complement inhibition, and are currently reserved for patients with refractory disease. In the recent past, there has been an active search for new antigens in myasthenia gravis, whereas clinical and experimental studies have provided new insights of crucial pathways in immune regulation, which might become the targets of future therapeutic interventions.
Gratton, Sean M; Herro, Angela M; Feuer, William J; Lam, Byron L
Myasthenia gravis is an autoimmune disease of the neuromuscular junction, commonly affecting the ocular muscles. Cigarette smoking has been shown to influence many autoimmune diseases, including multiple sclerosis and rheumatoid arthritis, but its effect on myasthenia gravis has not been well studied. We sought to determine whether cigarette smoking influenced disease-related symptoms in ocular myasthenia gravis (OMG). We performed a prospective, clinic-based cross-sectional study in a single academic neuro-ophthalmology practice. All patients diagnosed with OMG between November 2006 and April 2014 were included. A prospective telephone survey was administered to determine smoking status and myasthenia gravis-related symptom severity. The main outcome measure was the myasthenia gravis-specific activities of daily living (MG-ADL) score, a well-validated marker of symptoms and quality of life in myasthenia gravis. Forty-four patients were included in the analysis. Comparison of MG-ADL ocular subscores between current smokers (3.4 ± 2.6), former smokers (1.8 ± 2.1), and never smokers (1.1 ± 1.5) revealed a statistically significant relationship (P = 0.031) where current smokers had the highest MG-ADL ocular subscores and never smokers the lowest. Comparison of MG-ADL total scores revealed the same relationship (current 5.6 ± 4.5, former 2.9 ± 3.1, never 1.4 ± 2.5, P = 0.003). There were borderline significant correlations of pack years with MG-ADL ocular subscore (r = 0.27, P = 0.074) and MG-ADL total score (r = 0.30, P = 0.051). Our findings indicate an association between cigarette smoking and symptom severity in OMG. This association suggests that smoking cessation in OMG patients may lead to improved symptom-related quality of life.
E. D. Gasymly
Full Text Available Aim. To study the epidemiological features of myasthenia gravis in the Krasnoyarsk region.Materials and methods. 314 cases of myasthenia gravis, registered by the Krasnoyarsk regional health information analytical center, 87 of these patients were under constant monitoring.Results. Mean age of the patients was 45.4 (SD 4.5 years. The number of women in the observed group – 66 (75.86 %, which was 3 times more than men – 21 (24.14 %. The prevalence was 10.98 per 100.000 population, the primary incidence – 0.01 by 1000.Conclusion. Clinical features of the disease in the region were established, the register of patients with myasthenia was formed. From September 2016 a department of the neuromuscular pathology on the basis of advice Regional Hospital was formed.
Horigome, H; Nomura, T; Saso, K; Joh, T; Ohara, H; Akita, S; Sobue, S; Mizuno, Y; Kato, Y; Itoh, M
We present a case that suggests a relationship between primary biliary cirrhosis and myasthenia gravis. A 43-year-old Japanese woman was admitted to the Nagoya City University Medical School, First Department of Internal Medicine with abnormal liver function in August 1991. She had had ptosis of the right eye since 1990. She had not been treated for liver disease. Ptosis of the right eye and hepatomegaly were present. Serum laboratory examinations revealed elevated biliary enzymes and IgM levels; tests were positive for antimitochondrial antibody and antiacetylcholine antibody. Liver histology revealed chronic non-suppurative destructive cholangitis and led to a diagnosis of primary biliary cirrhosis. The tensilon test was positive. Electromyography with repetitive motor nerve stimulation revealed a neuromuscular junction defect; i.e., the primary characteristic of myasthenia gravis. The patient was diagnosed with myasthenia gravis. Although the development of myasthenia gravis has previously been reported in patients with primary biliary cirrhosis during D-penicillamine administration, this is a very rare case of the coexistence of both diseases before such treatment.
Tessitore, Adele; Vita, Maria Letizia; Cusumano, Giacomo; Congedo, Maria Teresa; Filotico, Mariella; Meacci, Elisa; Porziella, Venanzio; Margaritora, Stefano; Granone, Pierluigi
We describe the technique, the benefits and the drawbacks of an original video-assisted thymectomy (VAT), performed through an inframammary cosmetic incision and median sternotomy in myasthenia gravis (MG) patients. This procedure is clinically valuable and cosmetically satisfactory so as to be very well accepted by patients, especially by young women. Minimal-access thymectomy has become increasingly popular as surgical treatment for patients with nonthymomatous myasthenia gravis because of its comparable efficacy, safety, and lesser degree of tissue trauma with conventional open surgery. We report a review/interview of 180 MG patients treated between 1993 and 2005. According to Myasthenia Gravis Foundation of America (MGFA), complete stable remission (CSR) and pharmacologic remission (PR) were calculated at the end of a minimal period of 12 months. A clinical remission was obtained in 41.1% (CR 27.8%, PR 13.3%), who had been followed for at least 12 months from surgery. 95% of these patients judged their cosmetic results to be excellent or good. Thymectomy in MG video-assisted infra-mammary cosmetic incision has shown to be a useful surgical approach as demonstrated by the good functional and very good aesthetic results, associated with a very low morbidity and no mortality.
Pedersen, Emil Greve; Hallas, Jesper; Hansen, Klaus
We validated a new method of identifying patients with incident myasthenia in automated Danish registers for the purpose of conducting epidemiological studies of the disorder.......We validated a new method of identifying patients with incident myasthenia in automated Danish registers for the purpose of conducting epidemiological studies of the disorder....
Saidi, Trust; Sivarasu, Sudesh; Douglas, Tania S
Pharmacologic treatment of Myasthenia Gravis presents challenges due to poor tolerability in some patients. Conventional ptosis crutches have limitations such as interference with blinking which causes ocular surface drying, and frequent irritation of the eyes. To address this problem, a modular and adjustable ptosis crutch for elevating the upper eyelid in Myasthenia Gravis patients has been proposed as a non-surgical and low-cost solution. Areas covered: This paper reviews the literature on the challenges in the treatment of Myasthenia Gravis globally and focuses on a modular and adjustable ptosis crutch that has been developed by the Medical Device Laboratory at the University of Cape Town. Expert commentary: The new medical device has potential as a simple, effective and unobtrusive solution to elevate the drooping upper eyelid(s) above the visual axis without the need for medication and surgery. Access to the technology is provided through an open source platform which makes it available globally. Open access provides opportunities for further open innovation to address the current limitations of the device, ultimately for the benefit not only of people suffering from Myasthenia Gravis but also of those with ptosis from other aetiologies.
Fujimoto, Masafumi; Terasaki, Shuhei; Nishi, Masaaki; Yamamoto, Tatsuo
Several previous studies using univariate analysis have suggested that the pre-anaesthetic train-of-four (TOF) ratio, concentration of anti-acetylcholine receptor (AChR) antibodies and the presence of preoperative generalised muscular involvement are determinants of an increased response to neuromuscular blocking agents (NMBAs) in patients with myasthenia gravis. However, the determinants of the response of patients with myasthenia gravis to rocuronium, which is expected to be used more frequently since the advent of sugammadex, have not been studied. To clarify whether previously suggested determinants of the response to other intermediate-acting NMBAs would also affect the response to rocuronium and to reveal the determinants of the increased response to rocuronium in individual patients with myasthenia gravis using multivariate analysis. Case control study. Kumamoto University Hospital, November 2010 to September 2013. Thirty-eight patients with myasthenia gravis having surgery using a total intravenous anaesthetic technique were investigated. After induction of general anaesthesia, the 95% effective dose (ED95) of rocuronium was calculated using cumulative dose-finding methods. Neuromuscular function was monitored by acceleromyographic assessment of TOF responses of the adductor pollicis muscle to ulnar nerve stimulation. Patients were then divided into the increased response (ED95 rocuronium injection (baseline TOF ratio), concentration of anti-AChR antibodies, Osserman classification and treatment for myasthenia gravis in the two groups were compared. Stepwise logistic regression identified baseline TOF ratio and age of onset of myasthenia gravis as determinants of the increased response to rocuronium in patients with myasthenia gravis [odds ratios (95% confidence interval) of 0.87 (0.77 to 0.98; P = 0.02) and 0.92 (0.86 to 0.99; P = 0.03), respectively]. Multivariate analysis identified baseline TOF ratio and age of disease onset as determinants of
Full Text Available Myasthenia gravis is an autoimmune disorder that is characterized by muscle weakness that fluctuates, worsening with exertion, and improving with rest. Diagnosis of myasthenia gravis is made following clinical and physical examination and is confirmed by serum immunoassays to measure autoantibody levels. Myasthenia gravis especially when associated with pregnancy is a high-risk disease, and its course is unpredictable. We described the second report about use of sugammadex after rocuronium for a caesarean delivery with myasthenia gravis, but, unlike our case that formerly was diagnosed with myasthenia gravis, the patient was extubated on postoperative successfully and we did not encounter any respiratory problems. Resumo: Miastenia grave (MG é uma doença autoimune caracterizada por fraqueza muscular que flutua, piorando com o esforço físico e melhorando com o repouso. O diagnóstico de MG é feito após exame clínico e físico e confirmado por imunoensaios séricos para medir os níveis de autoanticorpos. MG, especialmente quando associada à gravidez, é uma doença de alto risco e de curso imprevisível. Descrevemos o segundo relato sobre o uso de sugamadex após rocurônio para um parto cesário com miastenia grave, mas, ao contrário de nosso caso que foi previamente diagnosticado com miastenia grave, a paciente foi extubada com sucesso no pós-operatório sem qualquer problema respiratório. Keywords: Myasthenia gravis, Sugammadex, Pregnancy, Palavras-chave: Miastenia grave, Sugammadex, Gravidez
Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar
Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27-53 years. In our study 25 patients (32.89%) belonged to the age group of 21-30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA 1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% ( p =3.3x10 -8 ) to 94.6% ( p =2.2x10 -14 ) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA 1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low.
Sieb, J P
This paper provides a thorough overview of the current advances in diagnosis and therapy of myasthenia gravis (MG). Nowadays the term ‘myasthenia gravis’ includes heterogeneous autoimmune diseases, with a postsynaptic defect of neuromuscular transmission as the common feature. Myasthenia gravis should be classified according to the antibody specificity [acetylcholine, muscle-specific receptor tyrosine kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), seronegative], thymus histology (thymitis, thymoma, atrophy), age at onset (in children; aged less than or more than 50 years) and type of course (ocular or generalized). With optimal treatment, the prognosis is good in terms of daily functions, quality of life and survival. Symptomatic treatment with acetylcholine esterase inhibition is usually combined with immunosuppression. Azathioprine still remains the first choice for long-term immunosuppressive therapy. Alternative immunosuppressive options to azathioprine include cyclosporin, cyclophosphamide, methotrexate, mycophenolate mofetil and tacrolimus. Rituximab is a promising new drug for severe generalized MG. Emerging therapy options include belimumab, eculizumab and the granulocyte– macrophage colony-stimulating factor. One pilot study on etanercept has given disappointing results. For decades, thymectomy has been performed in younger adults to improve non-paraneoplastic MG. However, controlled prospective studies on the suspected benefit of this surgical procedure are still lacking. In acute exacerbations, including myasthenic crisis, intravenous immunoglobulin, plasmapheresis and immunoadsorption are similarly effective. PMID:24117026
Weijnen, FG; Bosman, F; van der Glas, HW; Kuks, JBM
Mastication was evaluated in patients with bulbar myasthenia gravis and compared with that of patients with ocular myasthenia gravis, patients in remission who previously suffered from bulbar symptoms, and healthy controls. Bulbar myasthenia gravis may impair mastication due to weakness of the
Niks, Erik H.; Kuks, Jan B. M.; Verschuuren, Jan J. G. M.
The epidemiology of myasthenia gravis subtypes and the frequency of antibodies to muscle-specific kinase (MuSK) was studied in patients with generalised myasthenia gravis without anti-acetylcholine receptor antibodies who had an onset of symptoms between 1990 and 2004 in a well-defined region in the
Full Text Available Introduction. Autoimmune polyglandular syndrome type 2 is defined as adrenal insufficiency associated with autoimmune primary hypothyroidism and/or with autoimmune type 1 diabetes mellitus, but very rare with myasthenia gravis. Case report. We presented a case of an autoimmune polyglandular syndrome, type 2 associated with myasthenia gravis. A 49-year-old female with symptoms of muscle weakness and low serum levels of cortisol and aldosterone was already diagnosed with primary adrenal insufficiency. Primary hypothyroidism was identified with low values of free thyroxine 4 (FT4 and raised values of thyroidstumulating hormone (TSH. The immune system as a cause of hypothyroidism was confirmed by the presence of thyroid antibodies to peroxidase and TSH receptors. Myasthenia gravis was diagnosed on the basis of a typical clinical feature, positive diagnostic tests and an increased titre of antibodies against the acetylcholine receptors. It was not possible to confirm the immune nature of adrenal insufficiency by the presence of antibodies to 21- hydroxylase. The normal morphological finding of the adrenal glands was an indirect confirmation of the condition as well as the absence of other diseases that might have led to adrenal insufficiency and low levels of both serum cortisol and aldosterone. Hormone replacement therapy, anticholinergic therapy and corticosteroid therapy for myasthenia gravis improved the patient’s general state of health and muscle weakness. Conclusion. This case report indicates a need to examine each patient with an autoimmune disease carefully as this condition may be associated with another autoimmune diseases.
Costa, Sandra; Rocha, Gustavo; Leitão, Andreia; Guimarães, Hercília
Identify perinatal risk factors for transient tachypnea and pneumonia in neonates, and compare the outcome of these clinical conditions during the Neonatal Intensive Care Unit (NICU) stay. Retrospective review of newborns admitted to a level III NICU, comparing patients with transient tachypnea, pneumonia and a control group of healthy neonates. We included 202 patients with transient tachypnea, 29 with pneumonia and 498 controls. Perinatal infectious risk factors were more frequent in patients with pneumonia than in transient tachypnea (p ventilatory support more frequently and for a longer period. Comparing with controls, Apgar score at one and five minutes was higher in controls than in patients with pneumonia (p0.032 and p newborns with transient tachypnea and pneumonia are indistinguishable at presentation but clinical evolution is significantly different. The presence of perinatal infectious risk supports the diagnosis of pneumonia. Low Apgar score at one and five minutes was associated with both diseases, suggesting that etiologic factors may already be present at birth.
Jonsson, Dagur Ingi; Pirskanen, Ritva; Piehl, Fredrik
Muscle fatigue associated with myasthenia gravis is caused by autoantibodies interfering with neuromuscular transmission. Immunomodulating treatment is widely used in moderate to severe myasthenia, although the use of newer biological drugs except rituximab is rare. We describe the effect of tocilizumab, a blocker of interleukin-6 signalling, in two female myasthenia patients with high titres of serum acetylcholine receptor antibodies and insufficient response to rituximab. The first patient had been treated with high dose immunoglobulins regularly for several years and the second patient had been treated both with different oral immune suppressants and immunoglobulins before testing a low dose of rituximab without significant clinical effect. Subsequent treatment with tocilizumab resulted in clinical improvement within a few months. The first patient was switched back to rituximab, which resulted in worsening until tocilizumab was restarted. Tocilizumab can be a therapeutic option in cases not responding to rituximab. Copyright © 2017 Elsevier B.V. All rights reserved.
Aline de Almeida Xavier Aguiar
Full Text Available A retrospective chart review was performed on patients diagnosed as having myasthenia gravis in Ceará State, Brazil and who were followed from October 1981 to June 2009. Clinical and epidemiologic aspects were evaluated. In this work, 122 patients were studied, of whom 85 (69.7% were females and 37 (30.3% were males. The disease duration ranged from five months to 50 years (8.9±8.1 years. Age at the first symptoms varied from 0 to 74 years (31.9±14.4 years. The first main symptoms and signs were ptosis, diplopia and limb weakness. Generalized myasthenia was the most common clinical presentation, but 5.1% (n=6 persisted as ocular myasthenia. Thymectomy was performed in 42.6% (n=52 of myasthenic patients. A thymoma was present in 10 patients. Serum acetylcholine receptor (AChR antibodies were present in 80% (n=20 of specimens tested. The data presented are similar to those of studies performed in other countries.
N. I. Shcherbakova
Full Text Available Letus present a unique clinical case course of autoimmune non paraneoplastic myasthenic syndrome of Lambert–Eaton on the background of pregnancy, in the 24 years old patient, with a 3-year history of the disease. Throughout the pregnancy, birth and early postpartum period, patient was taking a stable unmodified drug therapy, which allowed observing "natural" course for neuromuscular disease. The first trimester of pregnancy proceeded without deterioration of the myasthenic syndrome. From the middle of the second trimester (19–20 weeks gestation, and the entire third trimester until parturition, the patient's condition for neuromuscular disease has improved, which was accompanied by an increase in strength of proximal limb muscles and the positive dynamics of the basic parameters of neuromuscular transmission. Deliveries came on ime, preceeded safely through vaginal delivery, without weakness of generic forces. There was born clinically healthy male child, weighing 2970 g, growth of 52 cm (7/8 Apgar score. However , on the second day in the newborn was marked negative dynamics of muscular hypotonia, extinction of neonatal reflexes, sucking weakness, episodes of apnea, which required tube feeding and non invasive oxygen support. Neuromuscular defect was transient in character and resolved within 5–7 days with administration in the morning hours of 20 mg of prednisone parenteral. The child was discharged with full recovery of function of the neuromuscular system on the 13th day breastfed. Shortly after birth the mother appeared in a state of negative dynamics: the increased weakness of the proximal muscles of the legs and arms, deteriorated parameters of the neuromuscular conduct. By analogy with myasthenia there appeared the similar influence of pregnancy on the Lambert Eaton myasthenic syndrome: 1 improvmem of the neuromuscular disease in II–III trimester of pregnancy, 2 intact ability to birth vaginally, 3 no evidence of
Torres-Vega, Estefanía; Mancheño, Nuria; Cebrián-Silla, Arantxa; Herranz-Pérez, Vicente; Chumillas, María J; Moris, Germán; Joubert, Bastien; Honnorat, Jérôme; Sevilla, Teresa; Vílchez, Juan J; Dalmau, Josep; Graus, Francesc; García-Verdugo, José Manuel; Bataller, Luis
To identify cell-surface antibodies in patients with neuromyotonia and to describe the main clinical implications. Sera of 3 patients with thymoma-associated neuromyotonia and myasthenia gravis were used to immunoprecipitate and characterize neuronal cell-surface antigens using reported techniques. The clinical significance of antibodies against precipitated proteins was assessed with sera of 98 patients (neuromyotonia 46, myasthenia gravis 52, thymoma 42; 33 of them with overlapping syndromes) and 219 controls (other neurologic diseases, cancer, and healthy volunteers). Immunoprecipitation studies identified 3 targets, including the Netrin-1 receptors DCC (deleted in colorectal carcinoma) and UNC5A (uncoordinated-5A) as well as Caspr2 (contactin-associated protein-like 2). Cell-based assays with these antigens showed that among the indicated patients, 9 had antibodies against Netrin-1 receptors (7 with additional Caspr2 antibodies) and 5 had isolated Caspr2 antibodies. Only one of the 219 controls had isolated Caspr2 antibodies with relapsing myelitis episodes. Among patients with neuromyotonia and/or myasthenia gravis, the presence of Netrin-1 receptor or Caspr2 antibodies predicted thymoma ( p myasthenia gravis, and neuromyotonia, often with Morvan syndrome ( p = 0.009). Expression of DCC, UNC5A, and Caspr2 proteins was demonstrated in paraffin-embedded thymoma samples (3) and normal thymus. Antibodies against Netrin-1 receptors (DCC and UNC5a) and Caspr2 often coexist and associate with thymoma in patients with neuromyotonia and myasthenia gravis. This study provides Class III evidence that antibodies against Netrin-1 receptors can identify patients with thymoma (sensitivity 21.4%, specificity 100%). © 2017 American Academy of Neurology.
Oger, Joel; Frykman, Hans
This review describes the state of the art for the use of laboratory testing in myasthenia gravis. The review brings a detailed description of the different clinical forms of auto-immune myasthenia and of the Lambert Eaton Myasthenic Syndrome (LEMS). They stress the differences between the different forms of acquired (auto-immune) myasthenia. Then they present a summary of the different antibodies found in the disease. They insist on the advantage of the RIPA assay to measure antibodies to the acetylcholine receptor. They stress the different types of contribution of each of these antibodies to the clinical diagnosis. They also describe the methods to measure each of the specific antibodies that have recently permitted to split the diagnosis: Abs to omega-conotoxin receptor in Lambert Eaton Myasthenic Syndrome (LEMS), abs to the acetylcholine receptor (AchR) in MG, Abs to muscle specific tyrosine kinase (MuSK) in Ab negative MG, and Abs to low molecular weight receptor related low-density lipo protein-4 (LRP-4). They also broach over the striated antibodies, less frequent and clinically less useful such as anti-titin, -ryanodine, -agrin and -rapsyn. This represent a 360° view of the field as presented in Toronto in October 2014. Copyright © 2015. Published by Elsevier B.V.
Maria F. Finnis
Full Text Available Myasthenia gravis (MG is an autoimmune disease in which antibodies are directed against the postsynaptic membrane of the neuromuscular junction, resulting in muscle weakness and fatigability. Juvenile myasthenia gravis (JMG is a rare condition of childhood and has many clinical features that are distinct from adult MG. Prepubertal children in particular have a higher prevalence of isolated ocular symptoms, lower frequency of acetylcholine receptor antibodies, and a higher probability of achieving remission. Diagnosis in young children can be complicated by the need to differentiate from congenital myasthenic syndromes, which do not have an autoimmune basis. Treatment commonly includes anticholinesterases, corticosteroids with or without steroid-sparing agents, and newer immune modulating agents. Plasma exchange and intravenous immunoglobulin (IVIG are effective in preparation for surgery and in treatment of myasthenic crisis. Thymectomy increases remission rates. Diagnosis and management of children with JMG should take account of their developmental needs, natural history of the condition, and side-effect profiles of treatment options.
Reynolds, Adam; O'Connell, Susan M; Kenny, Louise Clare; Dempsey, Eugene
We report a case of transient neonatal hypercalcaemia secondary to excess maternal vitamin D intake in pregnancy. Vitamin D insufficiency and deficiency in pregnancy are associated with adverse pregnancy outcomes, but there is no definite benefit to supplementation. The Royal College of Obstetrics and Gynaecology recommends routine supplementation with vitamin D 3 400 IU/day, but higher dose preparations usually recommended for the treatment of vitamin D deficiency are readily available over the counter. This case highlights the risks of excess supplementation, especially at higher doses and in women without evidence of vitamin D deficiency. The amount used in this case was at the upper end of the generally accepted safe dose range, but still less than that commonly recognised to cause problems. Neonatal hypercalcaemia is a potentially serious condition. The current local or national recommendations for vitamin D supplementation and the possible adverse effects of excess vitamin D consumption should be clearly communicated to pregnant women. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Kuks, JBM; Skallebaek, D
Plasmapheresis plays an important role in the acute management of patients with severe myasthenia gravis. Although plasmapheresis is now in use for more than 20 years, some controversies remain about the indication and the place in the therapy. It is generally found that the effect starts one week
Tajima, Shogo; Yanagiya, Masahiro; Sato, Masaaki; Nakajima, Jun; Fukayama, Masashi
Among human neoplasms, thymomas are well known for their association with paraneoplastic autoimmune diseases such as myasthenia gravis. However, regarding rare metaplastic thymoma, only one case of an association with myasthenia gravis has been reported. Here, we present the second case of a 44-year-old woman with metaplastic thymoma associated with myasthenia gravis. In metaplastic thymoma, intratumoral terminal deoxynucleotidyl transferase-positive T-cells (immature T-cells) are generally scarce, while they were abundant in the present case. We believe that these immature T-cells could be related to the occurrence of myasthenia gravis.
Stefanou, M I; Komorowski, L; Kade, S; Bornemann, A; Ziemann, U; Synofzik, M
Myasthenia gravis is an autoimmune neuromuscular disorder, which has only rarely been reported to co-manifest with myositis. The diagnosis of concomitant myositis in patients with myasthenia gravis is clinically challenging, and requires targeted investigations for the differential diagnosis, including EMG, autoantibody assays, muscle biopsy and, importantly, imaging of the mediastinum for thymoma screening. This report presents a case-vignette of a 72-year-old woman with progressive proximal muscle weakness and myalgias, diagnosed with thymoma-associated myasthenia and bioptically verified granulomatous myositis, with positive autoantibody status for ryanodine receptor and titin antibodies. The diagnosis of concurrent myositis and myasthenia gravis, especially in the presence of ryanodine receptor and titin antibodies, should lead neurologists to adopt different treatment strategies compared to those applied in myasthenia or myositis alone. Moreover, further evidence is warranted that titin and, particularly, ryanodine receptor antibodies may co-occur or be pathophysiologically involved in myasthenia-myositis cases.
Full Text Available Muscle-specific tyrosine kinase- (MuSK- antibodies-positive Myasthenia Gravis accounts for about one third of Seronegative Myasthenia Gravis and is clinically characterized by early onset of prominent bulbar, neck, shoulder girdle, and respiratory weakness. The response to medical therapy is generally poor. Here we report a case of late-onset MuSK-antibodies-positive Myasthenia Gravis presenting with signs of cognitive impairment and parkinsonism in addition to bulbar involvement and external ophthalmoplegia. The pattern of involvement of both peripheral and central nervous system dysfunction might suggest a common pathogenic mechanism, involving impaired cholinergic transmission.
Renton, Alan E.; Pliner, Hannah A.; Provenzano, Carlo; Evoli, Amelia; Ricciardi, Roberta; Nalls, Michael A.; Marangi, Giuseppe; Abramzon, Yevgeniya; Arepalli, Sampath; Chong, Sean; Hernandez, Dena G.; Johnson, Janel O.; Bartoccioni, Emanuela; Scuderi, Flavia; Maestri, Michelangelo; Raphael Gibbs, J.; Errichiello, Edoardo; Chiò, Adriano; Restagno, Gabriella; Sabatelli, Mario; Macek, Mark; Scholz, Sonja W.; Corse, Andrea; Chaudhry, Vinay; Benatar, Michael; Barohn, Richard J.; McVey, April; Pasnoor, Mamatha; Dimachkie, Mazen M.; Rowin, Julie; Kissel, John; Freimer, Miriam; Kaminski, Henry J.; Sanders, Donald B.; Lipscomb, Bernadette; Massey, Janice M.; Chopra, Manisha; Howard, James F.; Koopman, Wilma J.; Nicolle, Michael W.; Pascuzzi, Robert M.; Pestronk, Alan; Wulf, Charlie; Florence, Julaine; Blackmore, Derrick; Soloway, Aimee; Siddiqi, Zaeem; Muppidi, Srikanth; Wolfe, Gil; Richman, David; Mezei, Michelle M.; Jiwa, Theresa; Oger, Joel; Drachman, Daniel B.; Traynor, Bryan J.
IMPORTANCE Myasthenia gravis is a chronic, autoimmune, neuromuscular disease characterized by fluctuating weakness of voluntary muscle groups. Although genetic factors are known to play a role in this neuroimmunological condition, the genetic etiology underlying myasthenia gravis is not well understood. OBJECTIVE To identify genetic variants that alter susceptibility to myasthenia gravis, we performed a genome-wide association study. DESIGN, SETTING, AND PARTICIPANTS DNA was obtained from 1032 white individuals from North America diagnosed as having acetylcholine receptor antibody–positive myasthenia gravis and 1998 race/ethnicity-matched control individuals from January 2010 to January 2011. These samples were genotyped on Illumina OmniExpress single-nucleotide polymorphism arrays. An independent cohort of 423 Italian cases and 467 Italian control individuals were used for replication. MAIN OUTCOMES AND MEASURES We calculated P values for association between 8114394 genotyped and imputed variants across the genome and risk for developing myasthenia gravis using logistic regression modeling. A threshold P value of 5.0 × 10−8 was set for genome-wide significance after Bonferroni correction for multiple testing. RESULTS In the over all case-control cohort, we identified association signals at CTLA4 (rs231770; P = 3.98 × 10−8; odds ratio, 1.37; 95% CI, 1.25–1.49), HLA-DQA1 (rs9271871; P = 1.08 × 10−8; odds ratio, 2.31; 95% CI, 2.02 – 2.60), and TNFRSF11A (rs4263037; P = 1.60 × 10−9; odds ratio, 1.41; 95% CI, 1.29–1.53). These findings replicated for CTLA4 and HLA-DQA1 in an independent cohort of Italian cases and control individuals. Further analysis revealed distinct, but overlapping, disease-associated loci for early- and late-onset forms of myasthenia gravis. In the late-onset cases, we identified 2 association peaks: one was located in TNFRSF11A (rs4263037; P = 1.32 × 10−12; odds ratio, 1.56; 95% CI, 1.44–1.68) and the other was detected
Full Text Available Intestinal pseudo-obstruction is considered to be one of the most frequent gastrointestinal manifestations of myasthenia gravis, accompanied by the presence of neoplasia of the thymus gland in the vast majority of the cases presented in the international literature. Despite the fact that myasthenia gravis has been implicated to be the cause of recurrent episodes of intestinal pseudo-obstruction, adhesive ileus has never been reported to complicate this – in any sense rare – condition. We present a unique case of a patient with myasthenia gravis, free of thymus neoplasia, who was submitted to emergency surgery due to the presence of extended adhesive ileus as a complication of chronic intestinal functional obstruction.
Miarzynska, M.; Szlezak, L.; Fibak, J.; Wolski, M.; Lis-Podrzycka, E.; Miarzynski, K.
The rare case of malignant tumor of thymus - Thymoma malignum was described. The initial diagnosis was difficult, because of the irregular symptoms of myasthenia gravis. The diagnostic difficulties, treatment and clinical features of this neoplasm were also discussed. (author)
Hussain, N.; Ahmed, S.W.; Ahmed, T.; Hafeez, A.B.; Baloch, R.; Ali, S.
Objective: To determine the outcome of thymectomy in patients with myasthenia gravis and safety of median sternotomy approach. Methodology: An observational descriptive study was conducted in the department of thoracic surgery JPMC from February 2005 to January 2009. Twenty two patients having persistent generalized or ocular myasthenia gravis referred to our department by neurologists and general physicians, partially or not responding to medical treatment with or without thymoma, were included in the study. Those who were not fit for anaesthesia were excluded. Preoperatively 2 to 3 sessions of plasmaphaeresis were done and each patient was given anti myasthenia gravis treatment. Clinical staging was done by Modified Osserman classification. Median sternotomy approach was used. Outcome was assessed on the basis of remission of disease in different Osserman groups. All patients were followed for a minimum of 6 months. Results: Out of 22 patients, 16 (72.7%) were females and 6 (27.2%) males. Mean age at presentation was 35.2 +- 14.5 years. Mean duration of symptoms was 1.5 +- 1.2 years. A total of 4 (18.1%) patients with myasthenia gravis had thymoma and histopathology of 18 (81.9%) patients showed thymic hyperplasia. Remission was seen in most grades of Osserman. The best response was seen in Grade I where all patients achieved remission. Most patients in Grade II A and II B were benefited. The only patient in Grade III had no improvement of symptoms. No patient in Grade IV underwent thymectomy. Overall 86.3 % had a positive outcome on basis of remission and improvement. Conclusion: Thymectomy by median sternotomy is safe and effective with more favourable outcomes for patients of myasthenia gravis not responding to medical treatment. (author)
Sudulagunta, Sreenivasa Rao; Sepehrar, Mona; Sodalagunta, Mahesh Babu; Settikere Nataraju, Aravinda; Bangalore Raja, Shiva Kumar; Sathyanarayana, Deepak; Gummadi, Siddharth; Burra, Hemanth Kumar
Introduction: Myasthenia gravis (MG) is an antibody mediated autoimmune neuromuscular disorder characterized by fatigable muscle weakness. A proportion of myasthenia gravis patients are classified as refractory due to non responsiveness to conventional treatment. This retrospective study was done to evaluate clinical profile, epidemiological, laboratory, and features of patients with MG and mode of management using rituximab and complications. Methods: Data of myasthenia gravis patients admitted or presented to outpatient department (previous medical records) with MG between January 2008 and January 2016 were included. A total of 512 patients fulfilled the clinical and diagnostic criteria of myasthenia gravis of which 76 patients met the diagnostic certainty for refractory myasthenia gravis and were evaluated. Results: Out of 76 refractory MG patients, 53 (69.73%) patients fulfilled all the three defined criteria. The median age of onset of the refractory MG group was 36 years with a range of 27–53 years. In our study 25 patients (32.89%) belonged to the age group of 21–30 years. Anti-MuSK antibodies were positive in 8 non-refractory MG patients (2.06%) and 36 refractory MG patients (47.36%). Mean HbA1C was found to be 8.6±2.33. The dose of administered prednisone decreased by a mean of 59.7% (p=3.3x10–8) to 94.6% (p=2.2x10–14) after the third cycle of rituximab treatment. Conclusion: The refractory MG patients are most commonly female with an early age of onset, anti-MuSK antibodies, and thymomas. Refractory MG patients have higher prevalence and poor control (HbA1C >8%) of diabetes mellitus and dyslipidemia probably due to increased steroid usage. Rituximab is very efficient in treatment of refractory MG with adverse effects being low. PMID:27790079
Sund, K.K.; Skeie, G.O.; Gilhus, N.E.; Aarli, J.A.; Varhaug, J.E.
The authors have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group. The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data. 28 refs., 2 tabs
Boer, H.D. de; Egmond, J. van; Driessen, J.J.; Booij, L.H.D.J.
A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs
Full Text Available Based on long-term follow-up to perform comparative analysis of long-term results of surgical treatment of myasthenia. A retrospective analysis of long-term results of surgical treatment of 146 patients with myasthenia has been carried out. We used the modified Keynes classification to estimate the severity of myasthenia and to summarize the data relating to therapy volume and treatment results. In dependence on the type of thymus lesion patients were divided into two groups. Thymus hyperplasia was verified at — 106 (72.6 % patients, tumor lesion of the thymus gland (thymoma — at 40 (27.4 % ones. The results were estimated in the following periods after thymectomy: 1—2 years, 3—4 years, 5—6 years, 7 — 9 years, 10—14 years, and over 15 years. Short- and longterm results of surgical treatment of myasthenia for the patients without tumor lesions of the thymus gland were significantly better. Positive effects of surgical treatment of myasthenia in patients with hyperplasia are observed after 1 year of surgery (p = 0.0023, and the best results are observed after 5 — 6 year of the disease, then after 7 — 9 year one notes some deterioration of state (p = 0.026. In the myasthenia patients with thymoma one notes the similar trends in dynamics of state, but in general, the results are significantly (p = 0.042 badly than in the group of the patients with hyperplasia. Starting from the first year after operation treatment the patients with myasthenia with thymus hyperplasia have statistically significant (p = 0.048 decrease of average doses of glucocorticoids, and anticholinesterase drugs. The statistically best treatment results were noted for the patients operated at the first year of the disease. Positive result of surgical treatment of myasthenia is noted both in the short- and long-term period and at thymomas. In the group of patients with thymoma one has noted significantly badly results in comparison with group of hyperplasia. It is
S. I. Dedaev
Full Text Available Myasthenia gravis is a classic autoimmune disease, which clinical manifestations in the form of weakness and abnormal muscle fatigue, due to the damaging effect of polyclonal antibodies to different structures of the neuromuscular synapse and muscles. The study of autoimmune substrate with myasthenia is routine in many clinics dealing with the problems of neuromuscular pathology, and the identification of high concentration of serum antibodies to a number of antigenic structures is the gold standard in diagnosis.Determination of serum antibodies to various autoimmune targets is an important tool in clinical practice. The majority of patients shows the high concentration of antibodies to AchR that gives the opportunity to use it as an important diagnostic criterion. The specificity of changes in the concentration of AchR-antibodies due to pathogenetic treatment allows to objectify the suppression of autoimmune aggression and evaluate the reliability of remission. However, the absence of AchR-antibodies when there are clear clinical and electromyography signs of myasthenia gravis suggests an autoimmune attack against a number of other targets, the most studied of which is the MuSK. On the contrary, patients with myasthenia gravis associated with thymoma, almost always have a higher level of AchR-antibodies. The presence of thymoma is accompanied by the generation of antibodies to titin and RyR, which is also observed in persons with late-onset myasthenia without thymoma. High concentration of antibodies to these structures can be interpreted as a reliable sign of thymoma in patients younger than 60 years.
Gonzalez, Natalia L; Puwanant, Araya; Lu, Angela; Marks, Stanley M; Živković, Saša A
Immune checkpoint molecules are potent regulators of immunologic homeostasis that prevent the development of autoimmunity while maintaining self-tolerance. Inhibitors of immune checkpoint molecules are used as immunotherapy in the treatment of melanoma and different types of refractory cancer, and can trigger various autoimmune complications including myositis and myasthenia gravis. We describe a case of generalized myasthenia gravis induced by pembrolizumab and review 11 other cases. Five patients also had elevated serum CK levels ranging from 1200 to 8729 IU/L, and biopsy showed myositis in one. Severity was highly variable as symptoms normalized spontaneously in one patient, but three others developed myasthenic crisis (including two with fatal outcomes). Steroids have been recommended as a preferred treatment of autoimmune complications of immune-checkpoint inhibitors. Myasthenia gravis should be considered when weakness, diplopia or bulbar symptoms are seen after treatment with immune checkpoint inhibitors, and additional studies are needed to characterize association with hyperCKemia. Copyright © 2017 Elsevier B.V. All rights reserved.
Wirtz, P. W.; Sotodeh, M.; Nijnuis, M.; van Doorn, P. A.; van Engelen, B. G. M.; Hintzen, R. Q.; de Kort, P. L. M.; Kuks, J. B.; Twijnstra, A.; de Visser, M.; Visser, L. H.; Wokke, J. H.; Wintzen, A. R.; Verschuuren, J. J.
Background: Myasthenia gravis and the Lambert-Eaton myasthenic syndrome (LEMS) may have a similar distribution of muscle weakness. Deciding on a diagnosis of myasthenia gravis or LEMS on clinical grounds may therefore be difficult. Objective: To compare the localisation of initial muscle weakness
Howard, James F; Utsugisawa, Kimiaki; Benatar, Michael
BACKGROUND: Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients...... with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. METHODS: We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76...... hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease...
Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M.
Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications
Kaplan, I.; Blakely, B.T.; Pavlath, G.K.; Travis, M.; Blau, H.M. (Stanford Univ. School of Medicine, CA (USA))
Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. The authors show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. The results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also a direct effect on muscle. They propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.
Linda L Kusner
Full Text Available The mechanisms that underlie the development and maintenance of autoimmunity in myasthenia gravis are poorly understood. In this investigation, we evaluate the role of survivin, a member of the inhibitor of apoptosis protein family, in humans and in two animal models. We identified survivin expression in cells with B lymphocyte and plasma cells markers, and in the thymuses of patients with myasthenia gravis. A portion of survivin-expressing cells specifically bound a peptide derived from the alpha subunit of acetylcholine receptor indicating that they recognize the peptide. Thymuses of patients with myasthenia gravis had large numbers of survivin-positive cells with fewer cells in the thymuses of corticosteroid-treated patients. Application of a survivin vaccination strategy in mouse and rat models of myasthenia gravis demonstrated improved motor assessment, a reduction in acetylcholine receptor specific autoantibodies, and a retention of acetylcholine receptor at the neuromuscular junction, associated with marked reduction of survivin-expressing circulating CD20+ cells. These data strongly suggest that survivin expression in cells with lymphocyte and plasma cell markers occurs in patients with myasthenia gravis and in two animal models of myasthenia gravis. Survivin expression may be part of a mechanism that inhibits the apoptosis of autoreactive B cells in myasthenia gravis and other autoimmune disorders.
Whereas the coexistence of different autoimmune or rheumatologic diseases with myasthenia gravis (MG) is well documented, its combination with sarcoidosis is extremely rare. Presented here is an interesting case with coexisting MG and sarcoidosis.
J Gordon Millichap
Full Text Available A late infantile case of myasthenia gravis (MG with anti-muscle-specific receptor tyrosine kinase (MuSK high antibody (Ab titer is reported from Kyushu University, Fukuoka; and Nagasaki University, Japan.
Oren, Asaf; Wang, Michael K; Brnjac, Lori; Mahmud, Farid H; Palmert, Mark R
To examine a large population of infants with mild neonatal hyperthyrotrophinaemia (MNH) and determine prevalence, clinical characteristics and treatment history. Retrospective study of infants with MNH followed at The Hospital for Sick Children between 2000 and 2011. MNH was defined by an abnormal newborn screen followed by thyroid-stimulating hormone (TSH) between 5 and 30 mU/l and normal free T4 (FT4) on confirmatory tests. Mild neonatal hyperthyrotrophinaemia represented 22·3% of patients (103/462; 60 boys, 43 girls) within our clinic. Incidence increased from two of 20 in 2000 to 31 of 74 cases in 2010. Seventy eight percent of patients started L-thyroxine (initial dose: 8·3 ± 2·5 mcg/kg). The treated group had higher confirmatory TSH levels (P = 0·001) and had undergone thyroid scintigraphy more often (P = 0·0001) compared with the nontreated group. Evidence of overtreatment was detected in 45% of thyroid function tests obtained during treatment. Among the treated infants who had reached 3 years of age, 45% (N = 14) underwent a trial-off medication. Compared with those not trialled-off therapy, these infants were less likely to have had dose escalations during treatment (P = 0·001). The trial-off treatment was successful in 50% of cases. In the subset of infants with confirmatory TSH >10 mU/l, trial-off therapy was successful in 40%. None of the assessed variables predicted success of trial-off therapy. Mild neonatal hyperthyrotrophinaemia is an increasingly common diagnosis. It is more common in males and is often transient, but predictors of success of trial-off therapy were not identified. Further studies are needed to determine optimum L-thyroxine dosing and to determine whether treatment improves neurocognitive outcomes. © 2013 John Wiley & Sons Ltd.
Zhu, Kai; Li, Jiaoxing; Huang, Xin; Xu, Wei; Liu, Weibin; Chen, Jiaxin; Chen, Pei; Feng, Huiyu
Ocular myasthenia gravis, an autoimmune disease, is characterized by extraocular muscle weakness. Myasthenia gravis is closely associated with the functional status of the thymus gland. The efficacy of thymectomy for non-thymomatous ocular myasthenia gravis remains controversial. Here, we present the first systematic review and meta-analysis of studies assessing the outcome of thymectomy in patients with non-thymomatous ocular myasthenia gravis and found that the pooled rate of complete stable remission was 0.5074 with considerable heterogeneity. Furthermore, subgroup analysis showed that the efficacy of thymectomy differed according to geographical location. Furthermore, thymectomy outcomes are better in children than they are in adults. Thymectomy clearly represents an effective treatment for patients with non-thymomatous ocular myasthenia gravis. However, more multicenter, randomized, controlled clinical trials are now required to confirm these conclusions.
Isabela de Souza Jardim
Com o objetivo de verificar a necessidade de aplicação dos testes de Emissões Otoacústicas Evocadas por Estímulos Transientes (EOAT) e Potencial Evocado auditivo de Tronco Encefálico (PEATEA) combinados e comparar a ocorrência de resultados " Passa" entre os grupos de berçário comum e de UTI-Neonatal, foram avaliados 150 recém-nascidos de berçário comum e 70 recém-nascidos de UTI-Neonatal. Os testes de EOAT e PEATEA apresentaram ocorrência de resposta semelhante quando os grupos foram analisa...
Du, Ailian; Huang, Shiqian; Zhao, Xiaonan; Feng, Kuan; Zhang, Shuangyan; Huang, Jiefang; Miao, Xiang; Baggi, Fulvio; Ostrom, Rennolds S; Zhang, Yanyun; Chen, Xiangjun; Xu, Congfeng
Myasthenia gravis is an autoimmune disorder of the neuromuscular junction manifested as fatigable muscle weakness, which is typically caused by pathogenic autoantibodies against postsynaptic CHRN/AChR (cholinergic receptor nicotinic) in the endplate of skeletal muscle. Our previous studies have identified CA3 (carbonic anhydrase 3) as a specific protein insufficient in skeletal muscle from myasthenia gravis patients. In this study, we investigated the underlying mechanism of how CA3 insufficiency might contribute to myasthenia gravis. Using an experimental autoimmune myasthenia gravis animal model and the skeletal muscle cell C2C12, we find that inhibition of CAR3 (the mouse homolog of CA3) promotes CHRN internalization via a lipid raft-mediated pathway, leading to accelerated degradation of postsynaptic CHRN. Activation of CAR3 reduces CHRN degradation by suppressing receptor endocytosis. CAR3 exerts this effect by suppressing chaperone-assisted selective autophagy via interaction with BAG3 (BCL2-associated athanogene 3) and by dampening endoplasmic reticulum stress. Collectively, our study illustrates that skeletal muscle cell CAR3 is critical for CHRN homeostasis in the neuromuscular junction, and its deficiency leads to accelerated degradation of CHRN and development of myasthenia gravis, potentially revealing a novel therapeutic approach for this disorder.
Shirai, Takushi; Sano, Tasuku; Kamijo, Fuminao; Saito, Nana; Miyake, Tomomi; Kodaira, Minori; Katoh, Nagaaki; Nishie, Kenichi; Okuyama, Ryuhei; Uhara, Hisashi
We reported an 81-year-old woman with metastatic melanoma, in whom myasthenia gravis and rhabdomyolysis developed after nivolumab monotherapy. The first symptom of myasthenia gravis was dyspnea. Ultrasonography detected hypokinesis of the bilateral diaphragm suggesting myasthenia gravis, although there was no abnormal finding of the lungs in computed tomography images. Acetylcholine receptor binding antibodies were low-titer positive in the preserved serum before administration of nivolumab, strongly suggesting that the myasthenia gravis was a nivolumab-related immune adverse event. Despite the remarkable clinical benefits of immune checkpoint inhibitors for patients with advanced melanoma, it is important to recognize unexpected immune-related adverse events. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: email@example.com.
Myasthenia Gravis (MG) is a disorder affecting components of the neuromuscular junction. Epidemiological studies show rising incidence and prevalence rates. The aim of this study was to determine the incidence and prevalence of MG in the Republic of Ireland. Data sources included patient lists from consultant neurologists and ophthalmologists, a neuroimmunology laboratory, general practitioners and the Myasthenia Gravis Association. A total of 1,715 cases were identified, of which 706 definite, probable or possible autoimmune and congenital MG cases were included. The overall prevalence rate from the data obtained is 15.38\\/100,000. The study demonstrated a female preponderance (female:male of 1.3: 1) and some geographical variation within Ireland. The average incidence rate for the years 2000 to 2009 was 11.3 per year; the rate for the current decade is 18 per year. The increasing number of diagnoses may be due to improved access to diagnostic investigations and increasing awareness of the clinical manifestations.
Full Text Available Vocal cord palsy can have myriad causes. Unilateral vocal cord palsy is common and frequently asymptomatic. Trauma, head, neck and mediastinal tumors as well as cerebrovascular accidents have been implicated in causing unilateral vocal cord palsy. Viral neuronitis accounts for most idiopathic cases. Bilateral vocal cord palsy, on the other hand, is much less common and is a potentially life-threatening condition. Myasthenia gravis, an autoimmune disorder caused by antibodies targeting the post-synaptic acetylcholine receptor, has been infrequently implicated in its causation. We report here a case of bilateral vocal cord palsy developing in a 68-year-old man with no prior history of myasthenia gravis 2 months after he was operated on for diverticulitis of the large intestine. Delay in considering the diagnosis led to endotracheal intubation and prolonged mechanical ventilation with attendant complications. Our case adds to the existing literature implicating myasthenia gravis as an infrequent cause of bilateral vocal cord palsy. Our case is unusual as, in our patient, acute-onset respiratory distress and stridor due to bilateral vocal cord palsy was the first manifestation of a myasthenic syndrome.
Mazzoli, Marco; Ariatti, Alessandra; Valzania, Franco; Kaleci, Shaniko; Tondelli, Manuela; Nichelli, Paolo F; Galassi, Giuliana
50%-60% of patients with ocular myasthenia gravis (OMG) progress to generalized myasthenia gravis (GMG) within two years. The aim of our study was to explore factors affecting prognosis of OMG and to test the predictive role of several independent clinical variables. We reviewed a cohort of 168 Caucasian patients followed from September 2000 to January 2016. Several independent variables were considered as prognostic factors: gender, age of onset, results on electrophysiological tests, presence and level of antibodies against acetylcholine receptors (AChR Abs), treatments, thymic abnormalities. The primary outcome was the progression to GMG and/or the presence of bulbar symptoms. Secondary outcomes were either achievement of sustained minimal manifestation status or worsening in ocular quantitative MG subscore (O-QMGS) or worsening in total QMG score (T-QMGS), assessed by Myasthenia Gravis Foundation of America (MGFA) quantitative scores. Changes in mental and physical subscores of health-related quality of life (HRQoL) were assessed with SF-36 questionnaire. Variance analysis was used to interpret the differences between AChR Ab titers at different times of follow up among the generalized and non-generalized patients. Conversion to GMG occurred in 18.4% of patients; it was significantly associated with sex, later onset of disease and anti-AChR Ab positivity. Antibody titer above the mean value of 25.8 pmol/mL showed no significant effect on generalization. Sex and late onset of disease significantly affected T-QMGS worsening. None of the other independent variables significantly affected O-QMGS and HRQoL. Sex, later onset and anti-AChR Ab positivity were significantly associated with clinical worsening.
Full Text Available Abstract Background Myasthenia gravis, an uncommon autoimmune syndrome, is commonly associated with thymus abnormalities. Thymomatous myasthenia gravis is considered to have worst prognosis and thymectomy can reverse symptoms if precociously performed. Case report We describe a case of a patient who underwent mitral valve repair and was found to have an occasional thymomatous mass during the surgery. A total thymectomy was performed concomitantly to the mitral valve repair. Conclusion The diagnosis of thymomatous myasthenia gravis was confirmed postoperatively. Following the surgery this patient was strictly monitored and at 1-year follow-up a complete stable remission had been successfully achieved.
Kuroda, Yoshikazu; Miyamoto, Mariko; Maki, Masako; Yamazaki, Toshiro.
35 cases of myasthenia gravis were studied with RI scintigraphy. 67 Ga-citrate was used in 34 patients and 76 Se-selenomethionine in 5 patients for thymus scintigraphy. RI scintigram was negative in non-tumorous thymus, regardless of the severity of illness and it was positive in seven of nine patients with thymomas. RI accumulation in thymus was found both in benign and malignant thymomas. RI seems to accumulated in lymphocytic and mixed thymus more than epithelial type. (author)
Sival, Deborah A; van Weerden, Tiemen W; Vles, Johan S H; Timmer, Albertus; den Dunnen, Wilfred F A; Staal-Schreinemachers, A L; Hoving, Eelco W.; Sollie, Krystyne M; Kranen-Mastenbroek, Vivianne J M; Sauer, Pieter J J; Brouwer, Oebele F
OBJECTIVE: In neonates with spina bifida aperta (SBA), leg movements innervated by spinal segments located caudal to the meningomyelocele are transiently present. This study in neonates with SBA aimed to determine whether the presence of leg movements indicates functional integrity of neuronal
LEMS) in the same patient is rarely described. This is a case report of a patient who initially presented with myasthenia gravis and later complicated with presumably auto-immune LEMS. The patient was noted to be HIV positive. The interest lies in ...
O'Sullivan, S S
We describe a patient with the diagnoses of acquired neuromyotonia, cutaneous lupus erythematosus and alopecia areata, occurring many years after a thymectomy for myasthenia gravis associated with a thymoma. We review the current literature on autoimmune conditions associated with myasthenia gravis and thymectomy. To our knowledge, this combination of multiple autoimmune conditions has not been reported previously.
Kassardjian, Charles D; Murray, Brian J; Kokokyi, Seint; Jewell, Dana; Barnett, Carolina; Bril, Vera; Katzberg, Hans D
The relationship between sleep and neuromuscular fatigue is understood poorly. The goal of this study was to evaluate the effects of napping on quantitative measures of neuromuscular fatigue in patients with myasthenia gravis (MG). Eight patients with mild to moderate MG were recruited. Patients underwent maintenance of wakefulness tests (MWT) and multiple sleep latency tests (MSLT). The Quantitative Myasthenia Gravis Score (QMGS) was measured before nap and after each nap to examine the effects of napping and sleep on neuromuscular weakness. Results showed that QMGS improves only after naps where patients slept more than 5 min but not where patients did not sleep or slept less than 5 min. Daytime napping mitigates neuromuscular fatigue in patients with MG, especially if patients slept for more than 5 min. Copyright © 2013 Wiley Periodicals, Inc.
Leishangthem, Lakshmi; Satti, Sudhakar Reddy
71-year-old woman with progressive left-sided, monocular diplopia and ptosis. Her symptoms mimicked ocular myasthenia, but she had an indirect carotid cavernous fistula (CCF). She was diagnosed with monocular myasthenia gravis (negative acetylcholinesterase antibody) after a positive ice test and started on Mestinon and underwent a thymectomy complicated by a brachial plexus injury. Months later, she developed left-sided proptosis and ocular bruit. She was urgently referred to neuro-interventional surgery and was diagnosed with an indirect high-flow left CCF, which was treated with Onyx liquid and platinum coil embolisation. Mestinon was discontinued. Her ophthalmic symptoms resolved. However, she was left with a residual left arm and hand hemiparesis and dysmetria secondary to a brachial plexus injury. Indirect CCF usually can present with subtle and progressive symptoms leading to delayed diagnosis or misdiagnosis. It is important for ophthalmologists to consider this differential in a patient with progressive ocular symptoms. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Kuroda, Yoshikazu; Miyamoto, Mariko (Tokyo Metropolitan Fuchu Hospital (Japan)); Maki, Masako; Yamazaki, Toshiro
35 cases of myasthenia gravis were studied with RI scintigraphy. /sup 67/Ga-citrate was used in 34 patients and /sup 76/Se-selenomethionine in 5 patients for thymus scintigraphy. RI scintigram was negative in non-tumorous thymus, regardless of the severity of illness and it was positive in seven of nine patients with thymomas. RI accumulation in thymus was found both in benign and malignant thymomas. RI seems to accumulated in lymphocytic and mixed thymus more than epithelial type.
Jung Jin Lee
Full Text Available Aim. To estimate the clinical significance of anti-acetylcholine receptor antibody (anti-AChR-Ab levels in suspected ocular myasthenia gravis. Methods. In total, 144 patients complaining of fluctuating diplopia and ptosis were evaluated for serum levels of anti-acetylcholine receptor antibody and their medical charts were retrospectively reviewed. Subjects were classified into three groups: variable diplopia only, ptosis only, and both variable diplopia and ptosis. We investigated serum anti-AChR-Ab titer levels and performed thyroid autoantibody tests. Results. Patients’ chief complaints were diplopia (N=103, ptosis (N=12, and their concurrence (N=29. Abnormal anti-AChR-Ab was observed in 21 of 144 patients (14.1%. Between the three groups, mean age, number of seropositive patients, and mean anti-AChR-Ab level were not significantly different (P=0.224, 0.073, and 0.062, resp.. Overall, 27.5% of patients had abnormal thyroid autoantibodies. Conclusion. The sensitivity of anti-AChR-Ab was 14.1% in suspected ocular myasthenia gravis and seropositivity in myasthenia gravis patients showed a high correlation with the presence of thyroid autoantibodies.
cardiomyopathy, may occur3,4 and cardiac and respiratory involvement have been documented as indices of worse ... The heart is not involved in myasthenia gravis and electrocardiographic findings remain normal .... transmission and of Motor neurons. In: Berhman. RE, Kliegman RM, Jenson HB eds. Nelson extbook of ...
Glathe, S.; Neufang, K.F.R.; Haupt, F.W.
Radiologic imaging in myasthenia gravis is used for the evaluation of pathologic changes of the thymus gland. Computed tomography can demonstrate tumors of the anterior mediastinum in nearly 90% and is therefore superior to conventional radiography.Because of the variety of size and shape of the normal thymus gland, differentiation between normal thymus, follicular hyperplasia and thymoma is rarely possible especially in younger patients. In elderly patients with myasthenia gravis and involution of the thymus gland tumors of the thymus are reliably detected by computed tomography, whereas the ability of computed tomography to predict the histological diagnosis is poor even with intravenous administration of contrast media. (orig.) [de
Howard, James F; Freimer, Miriam; O'Brien, Fanny; Wang, Jing Jing; Collins, Stephen R; Kissel, John T
A phase 2 study of eculizumab for treating myasthenia gravis (MG) used the quantitative myasthenia gravis score (QMG) and myasthenia gravis activities of daily living profile (MG-ADL) to evaluate baseline disease severity and treatment response. Correlations were then analyzed between these assessments. Patients were given eculizumab or placebo during the first 16-week treatment period of the crossover study, with treatment assignments reversed for the second treatment period following a 5-week washout. QMG and MG-ADL scores at baseline and endpoint of each treatment period generated correlation coefficients for baseline status and treatment response during eculizumab therapy. Correlation strength between QMG and MG-ADL scores was higher for treatment response (R = 0.726; 95% confidence interval, 0.264-0.907; P = 0.0036) than for assessing baseline disease status (R = 0.552; 95% confidence interval, -0.022-0.839; P = 0.0495). MG-ADL may be more sensitive for assessing treatment response than point-in-time disease status. Muscle Nerve 56: 328-330, 2017. © 2016 Wiley Periodicals, Inc.
Rahbek, Martin Amadeus; Mikkelsen, Erik Elgaard; Overgaard, Kristian; Vinge, Lotte; Andersen, Henning; Dalgas, Ulrik
It has not been established whether progressive resistance training (PRT) and aerobic training (AT) are feasible and efficient in myasthenia gravis (MG). Fifteen subjects with generalized MG (Myasthenia Gravis Foundation of America (MGFA) clinical classification II-IV) were randomly assigned to 20 training sessions during 8 weeks of either PRT or AT. Feasibility was evaluated based on adherence, drop-out rate, adverse events, and Quantitative Myasthenia Gravis (QMG) score. Twelve subjects (MGFA II, n = 11; MGFA III, n=1) completed the intervention with a mean adherence of 95 % ± 8. One dropout (PRT) could potentially be related to PRT. Both groups reported adverse events, including bulbar symptoms (n = 2) and increased fatigue (n = 3), but no change in QMG score was observed in either group. The PRT group showed increases in maximal strength and functional capacity. Eight weeks of moderate to high intensity AT and PRT were feasible for most patients with mild MG. Maximal strength and functional capacity increased in the PRT group. Muscle Nerve 56: 700-709, 2017. © 2017 Wiley Periodicals, Inc.
Lee, Ha Neul; Kang, Hoon-Chul; Lee, Joon Soo; Kim, Heung Dong; Shin, Ha Young; Kim, Seung Min; Sunwoo, Il Nam; Lee, Young-Mock
Juvenile myasthenia gravis presents before 18 years of age with different characteristics according to racial background and pubertal development. The authors aimed to determine the clinical characteristics of children and adolescents of Korean ethnicity with myasthenia gravis, and evaluate the presentation and clinical outcomes according to the sex and onset age of the patients. The authors recruited 88 Korean juvenile myasthenia gravis patients between September 2005 and August 2015. Worse clinical severity from presentation, more aggressive treatment strategies, and worse final treatment outcomes were noted in girls with postpubertal onset than in the other patients. The symptoms were milder (pure ocular presentation in 96.6% [85/88]) and the disease course was more benign (94.3% [83/88]) in this study than in the literature. The homogenous racial background might have contributed to these results. These findings highlight the influence of pubertal development and the need for timely and appropriate active treatment, including thymectomy, to improve prognosis. © The Author(s) 2016.
André P.C. Matta
Full Text Available Myasthenia gravis (MG is a relatively uncommon disorder with an annual incidence of approximately 7 to 9 new cases per million. The prevalence is about 70 to 165 per million. The prevalence of the disease has been increasing over the past five decades. This is thought to be due to better recognition of the condition, aging of the population, and the longer life span of affected patients. MG causes weakness, predominantly in bulbar, facial, and extra-ocular muscles, often fluctuating over minutes to weeks, in the absence of wasting, sensory loss, or reflex changes. The picture of fluctuating, asymmetric external ophthalmoplegia with ptosis and weak eye closure is virtually diagnostic of myasthenia. We report an atypical MG case with three semiological cardinal signs.
Szobor, A.; Fornet, B.
The 75 Se-seleno-methionine isotope thymus scanning was examined in a series of patients with myasthenia gravis. The patients were given 4 μC/kg hence a total of 250-300 μC 75 Se-seleno-methionine, intravenously. The method proved useful and informative in the diagnostics of myasthenia. Prior to thymectomy, the thymic tumour or a large gland could be observed and some hints could be gained for the biological activity of the gland. After the operation, the success of thymectomy could be checked and later a possible recidive could be shown or excluded. In non-operative cases the change in thymic activity could be followed which was an important sign of a malignant or tumorous growth of the thymus. (author)
Al-Hashel, Jasem Y; Ismail, Ismail Ibrahim; John, John K; Ibrahim, Mohammed; Ali, Mahmoud
Myasthenia gravis is an autoimmune disease characterized by muscle weakness due to autoantibodies affecting the neuromuscular junction. Co-occurrence of myasthenia gravis and schizophrenia is very rare and raises a challenge in management of both diseases. Antipsychotic drugs exhibit anticholinergic side effects and have the potentials of worsening myasthenia. Long-acting risperidone is an injectable atypical antipsychotic drug that has not been previously reported to worsen myasthenia gravis in literature. We report the first case report of worsening of myasthenia after receiving long-acting risperidone injection for schizophrenia in a 29-year-old female with both diseases. She started to have worsening 2 weeks following the first injection and her symptoms persisted despite receiving plasma exchange. This could be explained by the pharmacokinetics of the drug. We recommend that long-acting risperidone should be used with caution in patients with myasthenia gravis, and clinicians must be aware of the potential risks of this therapy. Copyright © 2016 Elsevier B.V. All rights reserved.
Bak, Mads; Boonen, Susanne E; Dahl, Christina; Hahnemann, Johanne M D; Mackay, Deborah J D G; Tümer, Zeynep; Grønskov, Karen; Temple, I Karen; Guldberg, Per; Tommerup, Niels
Transient neonatal diabetes mellitus 1 (TNDM1) is a rare imprinting disorder characterized by intrautering growth retardation and diabetes mellitus usually presenting within the first six weeks of life and resolves by the age of 18 months. However, patients have an increased risk of developing diabetes mellitus type 2 later in life. Transient neonatal diabetes mellitus 1 is caused by overexpression of the maternally imprinted genes PLAGL1 and HYMAI on chromosome 6q24. One of the mechanisms leading to overexpression of the locus is hypomethylation of the maternal allele of PLAGL1 and HYMAI. A subset of patients with maternal hypomethylation at PLAGL1 have hypomethylation at additional imprinted loci throughout the genome, including GRB10, ZIM2 (PEG3), MEST (PEG1), KCNQ1OT1 and NESPAS (GNAS-AS1). About half of the TNDM1 patients carry mutations in ZFP57, a transcription factor involved in establishment and maintenance of methylation of imprinted loci. Our objective was to investigate whether additional regions are aberrantly methylated in ZFP57 mutation carriers. Genome-wide DNA methylation analysis was performed on four individuals with homozygous or compound heterozygous ZFP57 mutations, three relatives with heterozygous ZFP57 mutations and five controls. Methylation status of selected regions showing aberrant methylation in the patients was verified using bisulfite-sequencing. We found large variability among the patients concerning the number and identity of the differentially methylated regions, but more than 60 regions were aberrantly methylated in two or more patients and a novel region within PPP1R13L was found to be hypomethylated in all the patients. The hypomethylated regions in common between the patients are enriched for the ZFP57 DNA binding motif. We have expanded the epimutational spectrum of TNDM1 associated with ZFP57 mutations and found one novel region within PPP1R13L which is hypomethylated in all TNDM1 patients included in this study. Functional
Triagem auditiva neonatal: incidência de deficiência auditiva neonatal sob a perspectiva da nova legislação paulista Neonatal auditory screening: the incidence of neonatal hearing impairment in the context of the new São Paulo legislation
Khalil Fouad Hanna
Full Text Available OBJETIVOS: identificar a incidência de recém-nascidos com deficiência auditiva, em maternidade particular da cidade de São Paulo. MÉTODOS: estudo de coorte transversal, realizado no período de 2004 a 2008, em maternidade localizada na zona sul da cidade de São Paulo, com 20.615 recém-nascidos de ambos os sexos, sem indicadores de risco para deficiência auditiva e submetidos à triagem auditiva neonatal. O teste foi realizado por intermédio das Emissões Otoacústicas Evocadas Transientes (EOAET. Os pacientes que falharam nas EOAET nas duas fases foram encaminhados para a realização do Potencial Evocado Auditivo do Tronco Encefálico (PEATE para a confirmação da deficiência auditiva neonatal. Empregou-se o Teste Exato de Fischer e o nível de significância adotado foi de 0,05 oupOBJECTIVES: to determine the incidence of hearing impairment in newborns, at a private maternity hospital in the city of São Paulo. METHODS: a cross-sectional cohort study was carried out covering the period between 2004 and 2008, at a maternity hospital located in the southern zone of the city of São Paulo, including 20,615 newborns of both sexes, with no risk factors for hearing impairment and who had undergone neonatal auditory screening. The test was carried out using the Evoked Transient Otoacoustic Emissions test. Patients who failed both phases of this test were referred to do a Brainstem Auditory Evoked Potential test to confirm the presence of neonatal auditory deficiency. Fischer 's exact test was used with a level of significance of 0.05 orp<0.05. RESULTS: the incidence of neonatal hearing impairment found in this study was 1.2/1000. CONCLUSION: state legislation allows neonatal auditory screening to be more effective in achieving early detection of neonatal hearing impairment. Neonatal auditory screening prevents future impairment of oral development and language acquisition in a social, professional and educational context.
Diaz, Andres; Black, Edward; Dunning, Joel
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was if thymectomy in non-thymomatous myasthenia gravis was of any benefit? Overall, 137 papers were found using the reported search, of which 16 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The outcome variables were similar in all of the papers, including complete stable remission (CSR), pharmacological remission, age at presentation, gender, duration of symptoms, preoperative classification (Oosterhius, Osserman or myasthenia gravis Foundation of America (MGFA)), thymic pathology, preoperative medications (steroids, immunosuppressants), mortality and morbidity. We conclude that evidence-based reviews have shown that relative rates of thymectomy patients compared with non-thymectomy patients attaining outcome indicate that the former group of patients is more likely to achieve medication-free remission, become asymptomatic and clinically improve (54%, P benefit rate (BR), P benefits has not been established due to factors such as the confounding differences between myasthenia gravis patients receiving and not receiving thymectomy, the non-randomized nature of class II studies and the lack of Class I evidence to support its use. There is currently a randomized trial ongoing looking at thymectomy by sternotomy vs controls and the results are eagerly awaited.
Aim:To evaluate the management of post thymectomy myasthenia gravis (MG) patient in our centre; to highlight those aspects of patient care that could improve outcome and to serve as a bench mark for developing a standardized protocol for management. Method: A retrospective study of 5 cases of post thymectomy MG ...
Hye Young Jin
Full Text Available Transient neonatal diabetes mellitus (TNDM has been associated with paternal uniparental isodisomy of chromosome 6, paternally inherited duplication of 6q24, or a methylation defect at a CpG island of the ZAC or HYMAI gene. We experienced a case of TNDM in which the patient presented with hyperglycemia, macroglossia, and intrauterine growth retardation, caused by a paternally derived HYMAI. An 18-day-old female infant was admitted to the hospital because of macroglossia and recurrent hyperglycemia. In addition to the macroglossia, she also presented with large fontanelles, micrognathia, and prominent eyes. Serum glucose levels were 200–300 mg/dL and they improved spontaneously 2 days after admission. To identify the presence of a maternal methylated allele, bisulfite-treated genomic DNA from peripheral blood was prepared and digested with BssHII after polymerase chain reaction (PCR amplification with methylation-specific HYMAI primers. PCR and restriction fragment length polymorphism analysis showed that the patient had only the paternal origin of the HYMA1 gene. TNDM is associated with a methylation defect in chromosome 6, suggesting that an imprinted gene on chromosome 6 is responsible for this phenotype.
Mariana Inés Ybarra
Full Text Available OBJECTIVE: To investigate the prevalence of psychiatric disorders in patients with myasthenia gravis (MG. METHOD: Forty-one patients with MG answered to a structured psychiatric interview (MINI-Plus. RESULTS: Eleven (26.1% patients were diagnosed with a depressive disorder and 19 (46.3% were diagnosed with an anxiety disorder. Patients with dysthymia were older (p=0.029 and had longer disease duration (p=0.006. Patients with social phobia also had longer disease duration (p=0.039. CONCLUSION: Psychiatric disorders in MG are common, especially depressive and anxiety disorders.
De Roxas, Ranhel C; Bagnas, Marjorie Anne C; Baldonado, Jobelle Joyce Anne R; Rivera, Jonathan P; Roxas, Artemio A
Myasthenia gravis is an autoimmune neuromuscular disorder characterized by the production of abnormal autoantibodies directed against the receptors present in the neuromuscular junction. It has been the standard practice to offer thymectomy in all generalized myasthenia gravis patients despite the lack of robust evidence. The objectives of this study are to describe the clinical profile and differentiate the clinical outcomes of thymectomy versus non-thymectomy and thymomatous versus non-thymomatous myasthenia gravis patients in the Philippine General Hospital. Between 2009 and 2014, a total of 69 postthymectomy and 16 non-thymectomy patient records were successfully retrieved. The demographic characteristics, surgical approach, and histopathologic results were obtained. The clinical outcome after 6 months or 1 year-follow-up was also determined and grouped according to the following: (1) complete remission, (2) pharmacological remission, (3) no clinical change, (4) worsening symptoms, and (5) mortality. Majority of the patients were females (68.0%) with a mean age of 39.8 years and a mean duration of myasthenic symptoms of 21 months. Using the Myasthenia Gravis Foundation of America classification, 54.1% of patients fell under Class II and 48.2% of them presented with generalized weakness. In this study, 60.8% of postthymectomy myasthenia gravis patients had either complete remission or pharmacologic remission compared with 12.5% among non-thymectomy patients (p-value myasthenia gravis after thymectomy (p-value = 0.29). This study showed that both thymomatous and non-thymomatous myasthenia gravis patients who underwent thymectomy had a higher incidence of complete stable remission and pharmacologic remission as compared with myasthenia gravis patients who did not undergo thymectomy.
Full Text Available BACKGROUND Von Hippel-Lindau disease (VHL is a rare autosomal dominant inherited disorder characterized by an increased risk of tumours in a number of locations (eyes, brain, adrenal gland, pancreas, liver, kidneys, or other areas of the body. It is caused by germline mutation in the VHL gene. The VHL gene is a tumour suppressor gene that has been identified on the short arm of chromosome 3. CASE REPORT We report a case of a 60 year-old female with the clinical diagnosis of VHL type 1 (cerebellar haemangioblastoma, pancreatic cysts with subsequent steatorrhoea, and bilateral renal carcinoma who developed weakness and fatigability of skeletal muscles, left lid ptosis, snarling expression and nasal timbre speech. Acetylcholine receptor antibodies were negative in serum, while the electrodiagnostic test demonstrated an alteration of neuromuscolar junction which was consistent with the diagnosis of myasthenia gravis. Contrast-enhanced TC scan of the anterior mediastinum was performed, which excluded thymus enlargement. VHL gene evaluation in this patient identified a new mutation (c279delC9 and polymorphism c291C>G. At present the patient still suffers from ataxia and dysmetria due to cerebellar involvement in VHL, while fatigue and lid ptosis improved after the treatment with oral pyridostigmine 60 mg tid. DISCUSSION AND CONCLUSIONS To our knowledge this is the first report of a case of VHL associated with myasthenia gravis without thymoma. A case of VHL associated with a form of myasthenia gravis related to thymoma has been recently reported. In our case the absence of acetylcholine receptor antibodies may suggest a genetic origin also for the myasthenia gravis.
Gagua, R.; Todua, F.; Kuchava, V.; Gzirishvili, L.; Tsivtsivadze, G.; Vashakidze, M.
The aim of this work is to improve the results of diagnosis and surgical treatment of mediastinal thymomas. With this reason, 128 patients with the tumors of thymus have been undergone operations at the Thoracic Department of the National Cancer Centre (NCC) of Georgia. Material and methods: Out of 128 patients, type A thymomas were diagnosed in 7, type AB - in 14, type B1 - in 52, typer B2 - in 32, type B3 - in 18 patients. Myasthenia was revealed in 51 patients. Most frequently myasthenia was found in type B1 (48.1%) and in type B2 (40.8%) thymomas while in type A and type AB - in 28.6% and in 28.5% correspondingly, but in type B3 myasthenia was found in 16.7%. Results: Helical Computerized Tomography (CT) is leading in diagnosis of mediastinal thymomas. Surgical method in the volume of thymomtymectomy is the best choice of treatment of thymomas and it is performed basically by sternotomic approach. The effectiveness of surgical treatment depended upon the optimization of patients presurgical preparing and it often included steroidal therapy and plasmapheresis. The period of post surgical liquidation of myasthenia signs was between 1 - 14 months. The remote results of treatment depend on histological type of tumor and its stage. At I-II stages of A and AB type thymomas, 100% of patients survived 5 and more years after radical operation, while in III stage - 86%. 5-year survival rate was 95-97% in thymomas of B1-3 types stage I, but at stage III it was no more than 38%. (author)
Ali Hassan, FCPS
Full Text Available Although rare, the co-occurrence of myasthenia gravis and preeclampsia during pregnancy is responsible for considerable maternal and foetal morbidity and mortality. Both careful selection of medications and a multidisciplinary approach are required for treating such cases. This study presents a case report of a patient with a known history of generalized myasthenia gravis who presented with preeclampsia at 33 weeks' gestation. Subsequently, the patient developed recurrent seizures that necessitated the use of multiple medications, including phenytoin, valproic acid, levetiracetam, and propofol. Magnesium sulphate was not administered due to its blocking effect on calcium channels at the neuromuscular junction. The patient underwent a caesarean section under spinal anaesthesia and gave birth to a baby with intrauterine growth restriction (IUGR. Blood pressure control was achieved with the administration of methyldopa and parenteral hydralazine, an increased dose of pyridostigmine, and intravenous immunoglobulin therapy. The status of the patient's myasthenia gravis remained stable. This case serves to highlight the conflicts in the management of these two disorders and suggests strategies to resolve these conflicts in clinical management.
Oct 10, 2013 ... Intraoperative myasthenia crisis was managed with neostigmine infusion. She was managed in ... but world-wide, it is twice as common in women as in men and frequently .... could be a challenge when they present for surgery. The ideal anaesthetic ... intravenous opioids, neuromuscular blocking drugs,.
Bouchikh, M; Zouaidia, F; Benhaddou, E H A; Mahassini, N; Achir, A; El Malki, H O
The receptor for advanced glycation end-products (RAGE) is a membranous immunoglobulin involved in the pathogenesis of numerous autoimmune diseases and tumors. The aim of this study was to investigate the possible involvement of RAGE in the pathogenesis of myasthenia gravis. This prospective study included 41 cases of myasthenia gravis treated at our institution between 2010 and 2015. There were 18 men and 23 women, with an average age of 36.44±14.47 years. The majority of patients (24.4%) were classified as IIb, according to MGFA scoring, and 21 of them required corticosteroid and/or immunosuppressive treatment. Assessment of RAGE in thymus specimens was done by immunohistochemistry using RAGE antibody (C-term). RAGE expression was assessed according to various clinical, paraclinical and pathological parameters. Histopathological studies found 18 thymomas, 17 hyperplasias and six other types of pathology. Expression of RAGE was negative/weak in 19 cases and moderate/strong in 22 cases. It was more important in thymoma type B2 (Pmyasthenia was short (P=0.04), and was not significantly related to either myasthenia clinical severity or preoperative treatment. Our results suggest that the RAGE pathway is involved in myasthenia gravis pathophysiology, especially at disease onset, and in forms with thymomas. Further studies would be indispensable to explore other aspects of this signaling pathway, especially the potential role of different ligands and soluble forms of RAGE. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Background. Myasthenia gravis (MG) is a treatable autoimmune disease characterised by fatiguable weakness of skeletal muscles. More than 85% of MG patients have antibodies to the acetylcholine receptor (AChR) at the neuromuscular junction or are seropositive for MG (SPMG). In the developed world the incidence of ...
Full Text Available An important problem in management of the case with myasthenia gravis (MG is the control of exacerbation. There are several possible causes of exacerbation of MG including the use of drug. Here, the authors report a case of MG exacerbation and diarrhea associated with erythromycin treatment.
Giraldo, Lilliana María; Duque, Camilo; Uribe, Carlos Santiago; Hernández, Olga Helena
Myasthenia gravis is an antibody-mediated autoimmune disease. Approximately 10-15% of patients present with a thymoma, the presence of which is associated with greater severity of symptoms, myasthenic crisis, and irresponsiveness to front-line therapy. A thymectomy is recommended in young patients with generalized myasthenia gravis and in all patients presenting with thymoma. The patient was a 43-year-old woman, who first showed symptoms of myasthenic crisis in 2005 and presented with invasive thymoma managed with thymectomy and radiotherapy. In the subsequent three years, the patient presented with severe symptoms and two myasthenic crises that required mechanical ventilation and immunoglobulin treatment. Contrast chest computed tomography examinations showed no recurrence. Between 2009 and 2012, the patient experienced decreased symptom severity. In 2013, the patient presented with an exacerbation of symptoms; a contrast chest magnetic resonance scan showed a lesion in the anterior mediastinum, previously observed in 2011, suggestive of residual tissue as opposed to fibrosis. Regular management was started with immunoglobulins; a positron emission tomography scan was inconclusive, requiring a new resection, which showed no evidence of tumor recurrence. Patients with myasthenia gravis and those with myasthenia-related thymoma both share thymectomy as an element of treatment. However, following the procedure, exacerbation or reappearance of symptoms does not necessarily represent new alterations in the thymus.
Full Text Available Electrical myotonia is known to occur in a number of inherited and acquired disorders including myotonic dystrophies, channelopathies, and metabolic, toxic, and inflammatory myopathies. Yet, electrical myotonia in myasthenia gravis associated with antibodies against muscle-specific tyrosine kinase (MuSK has not been previously reported. We describe two such patients, both of whom had a typical presentation of proximal muscle weakness with respiratory failure in the context of a significant electrodecrement in repetitive nerve stimulation. In both cases, concentric needle examination revealed electrical myotonia combined with myopathic motor unit morphology and early recruitment. These findings suggest that MuSK myasthenia should be included within the differential diagnosis of disorders with electrical myotonia.
Yang, D H; Su, Z Q; Chen, Y; Chen, Z B; Ding, Z N; Weng, Y Y; Li, J; Li, X; Tong, Q L; Han, Y X; Zhang, X
To assess the predictive value of the albumin to globulin ratio (AGR) in evaluation of disease severity and prognosis in myasthenia gravis patients. A total of 135 myasthenia gravis (MG) patients were enrolled between February 2009 and March 2015. The AGR was detected on the first day of hospitalization and ranked from lowest to highest, and the patients were divided into three equal tertiles according to the AGR values, which were T1 (AGR 1.53). The Kaplan-Meier curve was used to evaluate the prognostic value of AGR. Cox model analysis was used to evaluate the relevant factors. Multivariate Logistic regression analysis was used to find the predictors of myasthenia crisis during hospitalization. The median length of hospital stay for each tertile was: for the T1 21 days (15-35.5), T2 18 days (14-27.5), and T3 16 days (12-22.5) (Pmyasthenia gravis. At the multivariate Cox regression analysis, the AGR (Pmyasthenia gravis patients. Respectively, the hazard ratio (HR) were 4.655 (95% CI: 2.355-9.202) and 0.596 (95% CI: 0.492-0.723). Multivariate Logistic regression analysis showed the AGR (Pmyasthenia crisis. The AGR may represent a simple, potentially useful predictive biomarker for evaluating the disease severity and prognosis of patients with myasthenia gravis.
Liang, T; Boulos, M I; Murray, B J; Krishnan, S; Katzberg, H; Umapathy, K
Myasthenia gravis (MG) is an autoimmune neuromuscular disorder resulting from skeletal muscle weakness and fatigue. An early common symptom is fatigable weakness of the extrinsic ocular muscles; if symptoms remain confined to the ocular muscles after a few years, this is classified as ocular myasthenia gravis (OMG). Diagnosis of MG when there are mild, isolated ocular symptoms can be difficult, and currently available diagnostic techniques are insensitive, non-specific or technically cumbersome. In addition, there are no accurate biomarkers to follow severity of ocular dysfunction in MG over time. Single-fiber electromyography (SFEMG) and repetitive nerve stimulation (RNS) offers a way of detecting and measuring ocular muscle dysfunction in MG, however, challenges of these methods include a poor signal to noise ratio in quantifying eye muscle weakness especially in mild cases. This paper presents one of the attempts to use the electric potentials from the eyes or electrooculography (EOG) signals but obtained from three different forms of sleep testing to differentiate MG patients from age- and gender-matched controls. We analyzed 8 MG patients and 8 control patients and demonstrated a difference in the average eye movements detected between the groups. A classification accuracy as high as 68.8% was achieved using a linear discriminant analysis based classifier.
Holtsema, H; Mourik, J; Rico, RE; Falconi, [No Value; Kuks, JBM; Oosterhuis, HJGH
We carried out an epidemiological study on thr prevalence and annual incidence of myasthenia gravis on tropical islands Curacao and Aruba in the period 1980 1995. Twenty-one patients (seven men and 14 women) were identified. The point prevalence increased from 29 per million in 1980 to about 70 per
Tomulescu, Victor; Sgarbura, Olivia; Stanescu, Codrut; Valciu, Crisanda; Campeanu, Ana; Herlea, Vlad; Popescu, Irinel
The aim of this study was to analyze the 10-year results of thoracoscopic unilateral extended thymectomy (TUET) performed in nontumoral myasthenia gravis according to the Myasthenia Gravis Foundation of America recommendations. Thoracoscopic unilateral extended thymectomy has the benefits of a minimally invasive approach. Previous data have shown promising midterm results but long-term results were lacking. Two hundred forty patients with nontumoral myasthenia gravis who underwent surgery between 1999 and 2009 were eligible for the study. The mean follow-up was of 67 months (range: 12-125), 134 patients completed follow-up assessments more than 60 months after TUET. There were 39 males (16.3%) and 201 females (83.7%), with an age range from 8 to 60 years. The mean preoperative disease duration was 21.5 months. All patients underwent preoperative steroid therapy. Anticholinesterase drugs were required for 123 patients (51.3%), and immunosuppressive drugs were required for 87 (36.3%) patients. The pathologic findings were as follows: normal thymus in 13 patients (5.5%), involuted thymus in 65 patients (27%), and hyperplastic thymus in 162 patients (67.5%). The average weight of the thymus was 110 ± 45 g. Ectopic thymic tissue was found in 147 patients (61.3%). There was no mortality, and morbidity consisted of 12 patients (5%). Complete stable remission was achieved in 61% of the patients, and the cumulative probability of achieving complete stable remission was 0.88 at 10 years. With zero mortality, low morbidity, and comparable long-term results to open surgery, TUET can be regarded as the best treatment option for patients undergoing surgery for myasthenia gravis.
Makhoul, I.R.; Smolkin, T.; Sujov, P.; Shoshany, G.; Epelman, M.
Esophageal dilatation (ED) in neonates is rare. In the present case, ED was detected in a chest radiograph following repair of congenital diaphragmatic hernia (CDH) in a term neonate. A roentgenographic swallow study on the seventh day of life demonstrated ED and a sub-diaphragmatic stomach. The infant thrived adequately on enteral feeding. A swallow study on the twentieth day of life showed a normal-width esophagus with gastroesophageal reflux and small hiatus hernia. The longstanding herniated stomach in the fetus apparently caused kinking, edema, and obstruction of the gastroesophageal junction. This led to a significant ED and concealment of gastroesophageal reflux. We aim to arouse awareness about the occurrence of ED with CDH, and about its benign course under conservative management. (orig.)
Makhoul, I.R.; Smolkin, T.; Sujov, P. [Dept. of Neonatology, Rambam Medical Center and Rappaport Faculty of Medicine, Technion, Haifa (Israel); Shoshany, G. [Dept. of Pediatric Surgery, Rambam Medical Center and Rappaport Faculty of Medicine, Technion, Bat-Galim, Haifa (Israel); Epelman, M. [Dept. of Radiology, Rambam Medical Center and Rappaport Faculty of Medicine, Technion, Bat-Galim, Haifa (Israel)
Esophageal dilatation (ED) in neonates is rare. In the present case, ED was detected in a chest radiograph following repair of congenital diaphragmatic hernia (CDH) in a term neonate. A roentgenographic swallow study on the seventh day of life demonstrated ED and a sub-diaphragmatic stomach. The infant thrived adequately on enteral feeding. A swallow study on the twentieth day of life showed a normal-width esophagus with gastroesophageal reflux and small hiatus hernia. The longstanding herniated stomach in the fetus apparently caused kinking, edema, and obstruction of the gastroesophageal junction. This led to a significant ED and concealment of gastroesophageal reflux. We aim to arouse awareness about the occurrence of ED with CDH, and about its benign course under conservative management. (orig.)
Mohammad Etezad Razavi
Full Text Available Introduction: The aim of this study was to evaluate the efficacy of acupuncture therapy on relieving ocular symptoms in resistant Ocular Myasthenia Gravis (OMG. Case: In this pilot study, three patients with OMG were offered ten sessions of acupuncture therapy, twice weekly, while they received their routine medical treatment. Their symptoms included ptosis and diplopia. Subjective impression of changes was assessed based on Ocular-quantitative Myasthenia Gravis (QMG scoring before and after treatment sessions. Conclusion:All three patients enrolled in this study showed resolution of diplopia. Their subjective impression of symptoms was improved. However, the score of ptosis did not improve considerably. Acupuncture is another choice for reducing ocular symptoms besides conventional treatment in resistant Ocular Myasthenia Gravis (OMG. However, future randomized controlled trial studies are needed to approve this issue.
The prevalence of myasthenia gravis is low. The management implications of this disease in pregnant women are very challenging for anaesthetists. The objective is to highlight some of the challenges, the management and the lessons learnt during the management of this patient. This is a case report of a 31-year old ...
Full Text Available ObjectivesTo describe the clinical profile, clinical outcomes and factors that may affect the outcome of juvenile myasthenia gravis (JMG patients in southern China.MethodsWe reviewed information relating to JMG patients treated and evaluated at the First Affiliated Hospital, Sun Yat-sen University, between 1998 and 2015. The study involved 327 JMG patients who had been followed up for ≥1 year.ResultsOverall, 77.4% patients showed initial symptoms in the prepubertal period (<12 years. 306 patients showed only ocular symptoms at onset. By the final follow-up, 61 ocular myasthenia gravis (OMG patients (61/306, 19.9% had developed generalized myasthenia gravis (GMG. Anti-acetylcholine receptor antibodies (AChR-Ab titer was an independent risk factor for generalization. Eleven patients (3.4% experienced spontaneous remission, but four relapsed. Low-dose oral prednisone (0.25 mg/kg was administered when symptoms did not significantly improve after pyridostigmine treatment. Immunosuppressants were administered when prednisone was unsatisfactory. Optimal outcome was achieved in 59.6% of patients. Specifically, 60 patients (18.3% attained complete stable remission (CSR, 12 (3.7% attained pharmaceutical remission (PR, and 123 (37.6% attained minimal manifestation (MM. In total, 53 OMG patients (21.5% attained CSR, a significantly higher proportion than among the GMG patients (8.6%, P = 0.009. Moreover, 67.2% of patients with duration <2 years showed significant clinical improvement compared with 46.3% of those with duration >2 years (P < 0.001. Thymectomy did not exhibit definite efficacy for JMG patients.ConclusionThere was a low frequency of cases positive for AChR-Ab in the Chinese population. AChR-Ab titer was revealed as an independent risk factor for generalization. Low doses of prednisone could treat JMG effectively with few side effects.
de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.
Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis
de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.
Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.
Ptosis is the consequence of a general or an ophthalmologic pathology, whose etiological diagnosis and treatment can be complex. Eliminating life-threatening emergencies or chronic and severe diseases remain an obsession for the neurologist or the ophthalmologist. Autoimmune myasthenia gravis is a leading to evoke, ...
Kanatli, Irem; Akkaya, Bahar; Uysal, Hilmi; Kahraman, Sevim; Sanlioglu, Ahter Dilsad
Myasthenia Gravis is an autoantibody-mediated, neuromuscular junction disease, and is usually associated with thymic abnormalities presented as thymic tumors (~10%) or hyperplastic thymus (~65%). The exact role of thymus in Myasthenia Gravis development is not clear, yet many patients benefit from thymectomy. The apoptotic ligand TNF-Related Apoptosis-Inducing Ligand is thought to be involved in the regulation of thymocyte counts, although conflicting results are reported. We investigated differential expression profiles of TNF-Related Apoptosis-Inducing Ligand and its transmembrane receptors, Nuclear Factor-kB activation status, and apoptotic cell counts in healthy thymic tissue and pathological thymus from Myasthenia Gravis patients. All tissues expressed TNF-Related Apoptosis-Inducing Ligand and its receptors, with hyperplastic tissue having the highest expression levels of death receptors DR4 and DR5. No detectable Nuclear Factor-kB activation, at least via the canonical Protein Kinase A-mediated p65 Ser276 phosphorylation, was evident in any of the tissues studied. Apoptotic cell counts were higher in MG-associated tissue compared to the normal thymus. Possible use of the TNF-Related Apoptosis-Inducing Ligand within the concept of an apoptotic ligand-mediated medical thymectomy in thymoma- or thymic hyperplasia-associated Myasthenia Gravis is also discussed. Copyright © 2016 Elsevier B.V. All rights reserved.
Baglivo, Ilaria; Esposito, Sabrina; De Cesare, Lucia; Sparago, Angela; Anvar, Zahra; Riso, Vincenzo; Cammisa, Marco; Fattorusso, Roberto; Grimaldi, Giovanna; Riccio, Andrea; Pedone, Paolo V
In the mouse, ZFP57 contains three classical Cys2His2 zinc finger domains (ZF) and recognizes the methylated TGC(met)CGC target sequence using the first and the second ZFs. In this study, we demonstrate that the human ZFP57 (hZFP57) containing six Cys2His2 ZFs, binds the same methylated sequence through the third and the fourth ZFs, and identify the aminoacids critical for DNA interaction. In addition, we present evidences indicating that hZFP57 mutations and hypomethylation of the TNDM1 ICR both associated with Transient Neonatal Diabetes Mellitus type 1 result in loss of hZFP57 binding to the TNDM1 locus, likely causing PLAGL1 activation. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Soetje, G.; Brinkmann, G. (Kiel Univ. (Germany, F.R.). Abt. Radiologie); Striepling, E.; Engemann, R. (Kiel Univ. (Germany, F.R.). Abt. Allgemeine Chirurgie)
A 40-year old woman with an invasive thymoma and myasthenia gravis is described in this article. Chest-x-ray, CT and MRI of the mediastinum could not offer definite results on tumour malignancy. Radical surgical removal was the consequence. This revealed a tumour infiltration of the pleura and pericardium; hence an adjuvant irradiation must have been performed. Mestinon-treatment was afterwards gradually reduced. (orig.).
Fukuhara, Mitsuro; Higuchi, Mitsunori; Owada, Yuki; Inoue, Takuya; Watanabe, Yuzuru; Yamaura, Takumi; Muto, Satoshi; Hasegawa, Takeo; Suzuki, Hiroyuki
Microscopic thymomas, defined as epithelial proliferations smaller than 1 mm in diameter, characteristically occur in patients with myasthenia gravis without macroscopic thymic epithelial tumors. However, some clinical and pathological aspects of this entity are still unclear. This retrospective study includes five consecutive patients who had undergone extended thymectomy for myasthenia gravis at our institution from April 2007 to March 2016 and in whom microscopic thymomas were diagnosed by histopathological examination of the resected specimens. During the same period, we performed 32 extended transsternal thymothymectomies/thymectomies in patients with myasthenia gravis, including the above five cases. We here review 18 cases of microscopic thymoma, including our five cases and 13 previously reported cases. The incidence of previously undiagnosed microscopic thymoma in patients undergoing thymectomy for myasthenia gravis in our institution is 15.2%. Serum preoperative anti-acetylcholine receptor antibody (anti-AchR Ab) titers were abnormally high in all of our five cases h (74.4±53.3 nmol/L) and decreased significantly after surgery (11.7±13.5 nmol/L, P=0.037). We divided our cases into the following three groups: microscopic thymoma group (Group M), thymoma group (Group T) and non-thymic tumor group (Group N). The mean preoperative anti-AchR Ab titers of these groups were 74.4, 26.5, and 368 nmol/L, respectively. All these values decreased postoperatively. The mean anti-AchR Ab titer was significantly higher in Group M than in Group T (P=0.034). All five cases in Group M were found by post-operative pathological examination to have multifocal type A thymomas. Microscopic thymomas tend to be multifocal type A thymomas. Anti-AchR Ab titers decreased significantly in all groups. It is very important to both perform complete extended thymectomies in patients with myasthenia gravis and pathological examination of thin slices of thymic tissue to maximize detection
Van Berkel, Megan A; Twilla, Jennifer D; England, Bryan S
Myasthenic crisis is a rare, yet serious condition that carries a 3%-8% mortality rate. Although infection is a common cause of decompensation in myasthenia gravis, several antibiotics classes have also been associated with an exacerbation. Selecting antibiotics can be a daunting clinical task and, if chosen inappropriately, can carry significant deleterious consequences. Not only do clinicians have to focus on treating the underlying infection appropriately, but avoiding antibiotics that may potentiate a myasthenic crisis is also vital. An 85-year-old female with a history of myasthenia gravis presented to the emergency department (ED) with increasing generalized weakness and shortness of breath. Clinical work-up was consistent with a community-acquired pneumonia (CAP) diagnosis. Her medical history included a myasthenia gravis exacerbation shortly after receiving moxifloxacin for CAP. After reviewing the patient's allergies, as well as potential antibiotic triggers, the decision was made to treat with tigecycline. The patient responded well to tigecycline therapy and was deemed stable for discharge on day 4 of hospitalization. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Evaluation of the myasthenia gravis patient frequently originates in the ED. It is important for clinicians to be able to distinguish between an underlying illness and a myasthenic crisis. In the event of an infectious process causing clinical deterioration in a myasthenia patient, optimal antibiotic selection becomes paramount. This patient case highlights the addition of tigecycline to the armamentarium of therapies available to treat myasthenia gravis patients presenting to the emergency department with CAP. Copyright © 2016 Elsevier Inc. All rights reserved.
Druschky, K.F.; Stadler, H.W.; Daun, H.; Erlangen-Nuernberg Univ., Erlangen
Hyperplasia of the thymus gland is observed in 65% of all patients with myasthenia gravis, while the incidence of thymus tumor is reported to be 8.5-28%. Conventional radiological techniques provide little information in the diagnosis of mediastinal lesions. Even a clearly developed thymus tumor can escape clinical detection. Since March 1978 thoracic computer tomography has been performed in addition to X-rays of the chest in a series of 19 patients with myasthenia ravis, 10 women and 9 men ranging in age from 15-71 years and in 3 patients with suspected thymomas but without myasthenia gravis. These examinations were carried out with a Somatom II (Siemens) since September 1979. On the average 15-20 scans were made at the level of the upper two-third of the sternum. The chest X-rays in 2 planes revealed signs of a thymus tumor in 3 female patients. Thoracic computer tomography showed definite signs of a space-occupying lesion in the anterior mediastinum in 11 cases. At thymectomy 6 patients were found to have hyperplasia of the thymus, 2 patients had a benign thymoma and 3 patients a malignant thymoma. In 6 cases computer tomography showed only slight changes and in 5 patients no pathological findings could be demonstrated in the thymus gland. Thoracic computer tomography is a relatively harmless diagnostic measure without any risk for the patient. It has a high resolution and great accuracy in the evaluation of the thymus gland and is therefore the method of choice for the diagnosis of patients with myasthenia gravis. (orig.) [de
Druschky, K.F.; Stadler, H.W.; Daun, H.
Hyperplasia of the thymus gland is observed in 65% of all patients with myasthenia gravis, while the incidence of thymus tumor is reported to be 8.5-28%. Conventional radiological techniques provide little information in the diagnosis of mediastinal lesions. Even a clearly developed thymus tumor can escape clinical detection. Since March 1978 thoracic computer tomography has been performed in addition to X-rays of the chest in a series of 19 patients with myasthenia ravis, 10 women and 9 men ranging in age from 15-71 years and in 3 patients with suspected thymomas but without myasthenia gravis. These examinations were carried out with a Somatom II (Siemens) since September 1979. On the average 15-20 scans were made at the level of the upper two-third of the sternum. The chest X-rays in 2 planes revealed signs of a thymus tumor in 3 female patients. Thoracic computer tomography showed definite signs of a space-occupying lesion in the anterior mediastinum in 11 cases. At thymectomy 6 patients were found to have hyperplasia of the thymus, 2 patients had a benign thymoma and 3 patients a malignant thymoma. In 6 cases computer tomography showed only slight changes and in 5 patients no pathological findings could be demonstrated in the thymus gland. Thoracic computer tomography is a relatively harmless diagnostic measure without any risk for the patient. It has a high resolution and great accuracy in the evaluation of the thymus gland and is therefore the method of choice for the diagnosis of patients with myasthenia gravis.
Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas
Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of β-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/β-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity
Utsugisawa, Kimiaki; Nagane, Yuriko
Many patients with myasthenia gravis (MG) still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of oral corticosteroids, since full remission is not common. Our analysis demonstrated that disease severity, oral corticosteroids, and depressive state are the major factors negatively associated with QOL, and that QOL of MM status patients taking CSR and is a target of treatment. In order to achieve early MM or better status with prednisolne strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved status using low-dose oral corticosteroids and calcineurin inhibitors.
Full Text Available Abstract Ectopic cervical thymoma is rare and is often misdiagnosed as a thyroid tumor or other malignancy. Ectopic thymic tissue can be found along the entire thymic descent path during embryogenesis. However, a thymoma arising from such ectopic thymic tissue is extremely rare. Herein we report a patient with ectopic cervical thymoma and myasthenia gravis (MG and discuss the management.
Phillips, William D.; Vincent, Angela
Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms. PMID:27408701
Phillips, William D; Vincent, Angela
Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ) caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (Ig)G1 and IgG3 antibodies to the acetylcholine receptor (AChR). They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.
Laurinaviciene, Rasa; Christesen, Henrik Thybo; Bygum, Anette
Neonatal lupus erythematosus (NLE) is a rare, passively acquired autoimmune disease, caused by maternal autoantibodies. Characteristic clinical features of NLE are transient rash and congenital heart block (CHB), but also hematological abnormalities and hepatobiliary dysfunction may occur...
Werneck, L C
A study of 17 muscle biopsies from patients with myasthenia gravis was done, using freshfrozen section and histochemistry tecnics. It was found 15 abnormal muscle biopsies. The most common abnormality were small dark angular fibers, excess of lipids droplets outside the muscle membrane, changes in fiber size and type II fiber atrophy. These findings suggested denervation in 11 biopsies, type II fiber atrophy in 7, linfocyte infiltration in 4, fiber necrosis with fagocitosis in 1 and 2 were normal. Was noted a direct correlation between the disease duration and the severity of the histological abnormality. Two patients had tymoma. Congenital myasthenia gravis, rheumatoid arthritis, intersticial hypertrophic neuritis, Hashimoto tireoiditis and concomitance of myasthenic syndrome was found once in different patients.
Myasthenia gravis (MG) is an immunological disorder characterized by damaged acetylcholine receptors (AchR) due to antibody, which not only blocks the receptor site but also causes degenerations of the receptors.. It is closely associated with disorders of similar pathogenesis, such as pernicious anaemia, thyrotoxicosis, ...
Pedersen, E G; Pottegård, Anton; Hallas, J
BACKGROUND AND PURPOSE: To evaluate the association between the use of azathioprine and risk of cancer in patients with non-thymoma myasthenia gravis (MG) in a nationwide setting. METHODS: Case-control study based on population-based registries. Cases were patients with MG with a first time...
Full Text Available Myasthenia gravis (MG patients visiting outpatient clinics frequently complain of headache. However, there have been few reports on the relation between chronic headache and myasthenia gravis (MG. We aimed to investigate whether MG symptoms affect the development or worsening of chronic headache. Among the 184 MG patients who were followed at the MG clinics, tension-type headache was observed in 71 (38.6% patients and 9 (4.9% complained of migraine. Twenty-five (13.6% complained that headache appeared or was exacerbated after the MG onset. The investigation into differences in the clinical characteristics of the MG patients showed that women tended to suffer from MG-associated headache more often than men. Logistic regression analyses revealed that female gender and mild ocular symptoms were independently predictive of headache associated with MG. Our results suggest that treatment of chronic headache should be required to improve the quality of life in MG patients.
Hou Xiuyu; Xu Yonggang; Gao Hong; Li Ming; Li Gaofeng; Liu Mingyuan
Objective: To evaluate the change of myasthenia gravis(MG) during radiotherapy for patients with malignant thymomas. Methods: Forty-five with malignant thymomas patients with were analyzed. The median total dose was DT54.2 Gy in 1.8-2.0 Gy/fraction, 5 clays a week. Anti-cholinesterase, such as pyridostigmine was used to control the MG symptoms. Results: Forty-five patients completed radiotherapy on schedule except one from whom the treatment was was with drawn because of respiratory muscle involvement. Among these 44 patients, myasthenic symptom was relieved in 4 to various degrees, 4 progressed, 34 no change and 2 developed cholinergic crisis. Myasthenic symptom was not changed in one patient for whom radiotherapy had been standed before operation nor during the course of postoperative radiotherapy. Conclusions: A course of radiotherapy of DT54.2 Gy, on fractionation of DT1.8-2.0 Gy modal would not aggravate myasthenia. However, proper use of anti-cholinesterase, careful observation and timely drug-adjustment are necessary. (authors)
Luo, Mengchuan; Liu, Xiaofang; Meng, Huanyu; Xu, Liqun; Li, Yi; Li, Zhibin; Liu, Chang; Luo, Yue-Bei; Hu, Bo; Xue, Yuanyuan; Liu, Yu; Luo, Zhaohui; Yang, Huan
Abnormal CD4 + T cell activation is known to play roles in the pathogenesis of myasthenia gravis (MG). However, little is known about the mechanisms underlying the roles of lncRNAs in regulating CD4 + T cell. In this study, we discovered that the lncRNA IFNG-AS1 is abnormally expressed in MG patients associated with quantitative myasthenia gravis (QMG) and the positive anti-AchR Ab levels patients. IFNG-AS1 influenced Th1/Treg cell proliferation and regulated the expression levels of their transcription factors in an experimental autoimmune myasthenia gravis (EAMG)model. IFNG-AS1 could reduce the expression of HLA-DRB and HLA-DOB and they had a negative correlation in MG. Furthermore IFNG-AS1 influenced the expression levels of CD40L and CD4 + T cells activation in MG patient partly depend on effecting the HLA-DRB1 expression. It suggests that IFNG-AS1 may be involved in CD4 + T cell-mediated immune responses in MG. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Jens A. Petersen
Full Text Available We report a 54-year-old woman who suffered a commotio cerebri, whiplash injury and a chest trauma with sternal fracture due to a high-velocity car accident. Two months later, she developed unilateral ptosis and blurred vision, which worsened during the day. Multiple diagnoses were suggested, ranging from thoracic outlet syndrome towards depression. Symptoms persisted and five years later, the patient consulted a neurologist. Laboratory analysis revealed significantly elevated levels of antibodies to acetylcholine receptors, and the diagnosis of myasthenia gravis was made. Speculatively, the damage of retrosternal thymic remnants due to a sternal fracture might have precipitated the condition or exacerbated subclinical disease.
Full Text Available Introduction: Neonatal hypernatremia dehydration (NHD is a dangerous condition in neonates, which is accompanied by acute complications (renal failure, cerebral edema, and cerebral hemorrhage and chronic complications (developmental delay. Children begin learning language from birth, and hearing impairment interferes with this process. We assessed the hearing status of infants with hypernatremia dehydration. Materials and Methods: In a case-control study in 110 infants presenting at the Ghaem Hospital (Mashhad, Iran between 2007 and 2011, we examined the incidence of hearing impairment in infants suffering from hypernatremia dehydration (serum sodium >150 mEq/L in comparison with infants with normal sodium level (serum sodium ≤150 mEq/L. Results: Three of 110 cases examined in the study group showed a transient hearing impairment. A mean serum sodium level of 173mg/dl was reported among hearing-impaired infants. Conclusion: Transient hearing impairment was higher in infants with hypernatremia; although this difference was not significant (P>0.05. Hearing impairment was observed in cases of severe hypernatremia.
Guertler, K.F.; Janzen, R.W.C.; Hagemann, J.; Otto, H.F.
Computed tomography of the mediastinum was performed in 45 patients with myasthenia gravis. Surgery was carried out in fourteen. Amongst these, there were four thymomas, one thymolipoma, eight thymic hyperplasias and one normal thymus gland. A further patient, who did not have surgery, probably also had a thymic tumour. The normal thymus and thymic hyperplasia cannot be distinguished on computed tomography. Differentiation of small thymomas from normal thymus is not always possible. Invasion by thymomas can only be appreciated with large tumours.
Annapoorna, K; Anbalagan, J; Neelamohan, R; Vengatesh, G; Stanley, J; Amudha, G; Aruldhas, M M
The present study aims to identify the association between androgen status and metabolic activity in skeletal and cardiac muscles of adult rats with transient gestational/neonatal-onset hypothyroidism. Pregnant and lactating rats were made hypothyroid by exposing to 0.05% methimazole in drinking water; gestational exposure was from embryonic day 9-14 (group II) or 21 (group III), lactational exposure was from postnatal day 1-14 (group IV) or 29 (group V). Serum was collected for hormone assay. Androgen receptor status, Glu-4 expression, and enzyme activities were assessed in the skeletal and cardiac muscles. Serum testosterone and estradiol levels decreased in adult rats of groups II and III, whereas testosterone remained normal but estradiol increased in group IV and V, when compared to coeval control. Androgen receptor ligand binding activity increased in both muscle phenotypes with a consistent increase in the expression level of its mRNA and protein expressions except in the forelimb of adult rats with transient hypothyroidism (group II-V). Glut-4 expression remained normal in skeletal and cardiac muscle of experimental rats. Specific activity of hexokinase and lactate dehydrogenase increased in both muscle phenotypes whereas, creatine kinase activity increased in skeletal muscles alone. It is concluded that transient gestational/lactational exposure to methimazole results in hypothyroidism during prepuberal life whereas it increases AR status and glycolytic activity in skeletal and cardiac muscles even at adulthood. Thus, the present study suggests that euthyroid status during prenatal and early postnatal life is essential to have optimal AR status and metabolic activity at adulthood. © Georg Thieme Verlag KG Stuttgart · New York.
Myasthenia gravis is an autoimmune neuromuscular disorder. There are several treatment options, including symptomatic treatment (acetylcholinesterase inhibitors), short-term immunosuppression (corticosteroids), long-term immunosuppression (azathioprine, cyclosporine, cyclophosphamide, methotrexate, mycophenolate mofetil, rituximab, tacrolimus), rapid acting short-term immunomodulation (intravenous immunoglobulin, plasma exchange), and long-term immunomodulation (thymectomy). This review explores in detail these different treatment options. Potential future treatments are also discussed. PMID:21845054
Miarzynska, M.; Szlezak, L.; Fibak, J.; Wolski, M.; Lis-Podrzycka, E.; Miarzynski, K. [Szpital im. F. Raszei, Poznan (Poland)
The rare case of malignant tumor of thymus - Thymoma malignum was described. The initial diagnosis was difficult, because of the irregular symptoms of myasthenia gravis. The diagnostic difficulties, treatment and clinical features of this neoplasm were also discussed. (author)
Renata Mota Mamede Carvallo
Full Text Available ABSTRACT INTRODUCTION: Abnormalities in auditory function of newborns may occur not only because of preterm birth, but also from the use of medications and from diseases related to prematurity. OBJECTIVE: To analyze the inhibitory effect from stimulation of the olivocochlear efferent system on transient evoked otoacoustic emissions in preterm neonates, comparing these data with those from full-term neonates. METHODS: This was a prospective, cross-sectional, contemporary cohort study with 125 neonates, pooled into two groups: full-term (72 full-term neonates, 36 females and 36 males, born at 37-41 weeks of gestational age; and preterm (53 neonates, 28 males and 25 females, born at ≤36 weeks of gestational age, evaluated at the corrected gestational age of 37-41 weeks. Otoacoustic emissions were recorded using linear and nonlinear click-evoked stimuli, with and without contralateral stimulation. RESULTS: The inhibitory effect of the efferent pathway in otoacoustic emissions was different (p = 0.012 between groups, and a mean reduction of 1.48 dB SPL in full-term births and of 1.02 dB SPL in preterm births was observed for the non-linear click-evoked stimulus. CONCLUSION: The results suggest a reduced inhibitory effect of the olivocochlear efferent system on otoacoustic emissions in preterm neonates.
Bucuk, Mira; Gasparovic, Iva; Sonnenschein, Ivan; Perkovic, Olivio
Myasthenia gravis is a chronic autoimmune disease characterized by weakening of voluntary muscles during the day and a marked restitution of function during the night and after rest. The symptoms may worsen over days or weeks, sometimes even in a few hours, and are usually well controlled by appropriate therapy. Arachnoid cysts are congenital or acquired deformities of the arachnoid membrane and are usually too small to cause distinct clinical symptomatology. We describe a case of a 76-year-old myasthenia gravis patient with an arachnoid cyst. To the best of our knowledge this is the first reported case of these two comorbidities together.
Rodriguez, Sonia Pilar; Zuluaga, Claudia Patricia; Uriza, Luis Felipe C; Sanchez M, Jully Mariana
Thymoma are thymic tumors that arise from epithelial cells, they have different morphological characteristics. It is known for its association with autoimmune diseases such as myasthenia gravis, pure red cell aplasia, systemic lupus erythematosus, or hipogamaglobulinemia pemphigus foliaceus. The association thymoma-myasthenia gravis-pure red cell aplasia is a rare one; there will be a case report with the corresponding discussion and review of the literature
Gao, Feng; Zhao, Xue; Zhang, Jing; Cui, Xinzheng; Zhang, Yingna; Li, Qianru; Liu, Pingping; Fang, Hua; Du, Ying; Zhang, Qingyong; Yang, Junhong; Zhang, Yunke
Myasthenia gravis (MG) occurs globally, and many studies have indicated that there are regional differences in epidemiology, biomarkers, and prognosis of MG. A total of 478 patients with MG who visited hospitals in the Henan Province between January 2010 and February 2014 were included. Age, gender, age at onset, serum antibody, thymus pathology, treatment information, and Myasthenia Gravis Foundation of America (MGFA) classification were assessed. Compared with previous reports from other areas, we found some differences in MG patients from Henan. The proportion of childhood MG in our study was lower than other reports of Oriental patients with MG. There seems to be an association between onset age, muscle involvement, and acetylcholine receptor antibody levels. Thymectomy improved the symptoms in 78.5% of thymectomy-treated patients. These differences are likely related to geographical, environmental, and ethnic differences. Understanding these differences will help us to define more specific treatment. © 2016 Wiley Periodicals, Inc.
Maneh, Nidain; Apetse, Kossivi; Diatewa, Bénédicte Marèbe; Domingo, Sidik Abou-Bakr; Agba, Aidé Isabelle; Ayena, Koffi Didier; Balogou, Koffi Agnon; Balo, Komi Patrice
Myasthenia gravis is a rare acquired autoimmune pathology causing neuromuscular transmission impairment. Juvenile onset of myasthenia gravis is often characterized by ocular involvement. We report two cases of ocular juvenile myasthenia gravis (JMG) in two siblings. They were two young girls, XA and XB, aged 11 and 9 years, of Malian origin, residing in Togo, born from first-degree of consanguinity presenting to Ophthalmology due to progressive decrease in visual acuity. XA showed visual acuity 8/10 on both eyes while XB showed improvement in visual acuity from 3/10 to 7/10 using a pinhole occluder, suggesting ametropia. XA had a 2-year history of bilateral ptosis lifting the upper eyelid of 7 mm, while XB had a 3-year history of bilateral ptosis with no lifting of the upper eyelid. Ice pack test was strongly positive in both patients. They had Cogan's lid twitch with paresis of the oculomotor nerve without diplopia. The dosage of acetylcholine receptor autoantibodies was normal. The diagnosis of JMG associated with ametropia was suspected. Ametropia was corrected by glasses and a specific treatment with pyridostigmine was initiated, but both patients were lost to follow-up. Autoimmune myasthenia gravis with inaugural ophthalmologic manifestation is rare but it can occur among children living in sub-Saharan Africa. Studies should be conducted to establish the features of this disease.
Guertler, K.F.; Janzen, R.W.C.; Hagemann, J.; Otto, H.F.; Hamburg Univ.; Hamburg Univ.
Computed tomography of the mediastinum was performed in 45 patients with myasthenia gravis. Surgery was carried out in fourteen. Amongst these, there were four thymomas, one thymolipoma, eight thymic hyperplasias and one normal thymus gland. A further patient, who did not have surgery, probably also had a thymic tumour. The normal thymus and thymic hyperplasia cannot be distinguished on computed tomography. Differentiation of small thymomas from normal thymus is not always possible. Invasion by thymomas can only be appreciated with large tumours. (orig.) [de
Aydin, Yener; Ulas, Ali Bilal; Mutlu, Vahit; Colak, Abdurrahim; Eroglu, Atilla
In recent years, thymectomy has become a widespread procedure in the treatment of myasthenia gravis (MG). Likelihood of remission was highest in preoperative mild disease classification (Osserman classification 1, 2A). In absence of thymoma or hyperplasia, there was no relationship between age and gender in remission with thymectomy. In MG treatment, randomized trials that compare conservative treatment with thymectomy have started, recently. As with non-randomized trials, remission with thymectomy in MG treatment was better than conservative treatment with only medication. There are four major methods for the surgical approach: transcervical, minimally invasive, transsternal, and combined transcervical transsternal thymectomy. Transsternal approach with thymectomy is the accepted standard surgical approach for many years. In recent years, the incidence of thymectomy has been increasing with minimally invasive techniques using thoracoscopic and robotic methods. There are not any randomized, controlled studies which are comparing surgical techniques. However, when comparing non-randomized trials, it is seen that minimally invasive thymectomy approaches give similar results to more aggressive approaches. PMID:28416933
McGurgan, Iain J
Increased rates of NMSC (nonmelanoma skin cancer) have recently been reported in people with MG (myasthenia gravis) receiving azathioprine treatment. Guidelines on azathioprine for patients with dermatological and gastrointestinal disorders stress the importance of NMSC risk awareness and prevention. The aim of this study is to assess whether MG patients are being informed of this risk.
Picoli Souza, K. de [Faculdade de Ciências Biológicas e Ambientais, Universidade Federal da Grande Dourados, Dourados, MS (Brazil); Nunes, M.T. [Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade de São Paulo, São Paulo, SP (Brazil)
Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.
Picoli Souza, K. de; Nunes, M.T.
Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood
Souza, K de Picoli; Nunes, M T
Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.
K. de Picoli Souza
Full Text Available Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g and triiodothyronine (0.5-50 µg/100 g for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold. Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60% ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold, and decreased heart rate (5%, fast muscle myoglobin mRNA (30% and body weight (20% in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30% and body weight (14%. These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.
Chae, Chang-Suk; Kwon, Ho-Keun; Hwang, Ji-Sun; Kim, Jung-Eun; Im, Sin-Hyeog
Probiotics are live bacteria that confer health benefits to the host physiology. Although protective role of probiotics have been reported in diverse diseases, no information is available whether probiotics can modulate neuromuscular immune disorders. We have recently demonstrated that IRT5 probiotics, a mixture of 5 probiotics, could suppress diverse experimental disorders in mice model. In this study we further investigated whether IRT5 probiotics could modulate the progression of experimental autoimmune myasthenia gravis (EAMG). Myasthenia gravis (MG) is a T cell dependent antibody mediated autoimmune disorder in which acetylcholine receptor (AChR) at the neuromuscular junction is the major auto-antigen. Oral administration of IRT5 probiotics significantly reduced clinical symptoms of EAMG such as weight loss, body trembling and grip strength. Prophylactic effect of IRT5 probiotics on EMAG is mediated by down-regulation of effector function of AChR-reactive T cells and B cells. Administration of IRT5 probiotics decreased AChR-reactive lymphocyte proliferation, anti-AChR reactive IgG levels and inflammatory cytokine levels such as IFN-γ, TNF-α, IL-6 and IL-17. Down-regulation of inflammatory mediators in AChR-reactive lymphocytes by IRT5 probiotics is mediated by the generation of regulatory dendritic cells (rDCs) that express increased levels of IL-10, TGF-β, arginase 1 and aldh1a2. Furthermore, DCs isolated from IRT5 probiotics-fed group effectively converted CD4+ T cells into CD4+Foxp3+ regulatory T cells compared with control DCs. Our data suggest that IRT5 probiotics could be applicable to modulate antibody mediated autoimmune diseases including myasthenia gravis. PMID:23284891
Ezzatian-Ahar, Shabnam; Pedersen, Emil Arnspang; Schrøder, Henrik Daa
We present the case of a 33-year-old woman who within weeks developed severe swallowing difficulties and weakness in her limbs to an extent requiring hospitalization. Workup confirmed clinically suspected diagnoses of polymyositis and autoimmune myasthenia. A suspicion of malignant thymoma based ...
Citirak, Gülsenay; Cejvanovic, Sanja; Andersen, Henning
INTRODUCTION: The aim of this observational, cross-sectional study was to quantify the potential presence of muscle weakness among patients with generalized myasthenia gravis (gMG). The influence of gender, treatment intensity and disease duration on muscle strength and disease progression was also...
Ezzatian-Ahar, Shabnam; Pedersen, Emil Arnspang; Schrøder, Henrik Daa
We present the case of a 33-year-old woman who within weeks developed severe swallowing difficulties and weakness in her limbs to an extent requiring hospitalization. Workup confirmed clinically suspected diagnoses of polymyositis and autoimmune myasthenia. A suspicion of malignant thymoma based...
Skedros, John G; Kiser, Casey J; Mendenhall, Shaun D
This report describes a patient who had a series of daily interscalene nerve blocks to treat pain following a shoulder manipulation for postsurgical stiffness. She experienced acute respiratory compromise that persisted for many weeks. All typical and unusual causes of these symptoms were ruled out. Her treating pulmonologist theorized that the ipsilateral carotid body had been injured. However, it was subsequently determined that the constellation of symptoms and their prolonged duration were best explained by a poor stress response from Addison's disease coupled with exacerbation of early onset myasthenia gravis. This patient's case is not a typical reaction to interscalene nerve blocks, and thus preoperative testing would not be recommended for myasthenia gravis or Addison's disease without underlying suspicion. We describe this report to inform physicians to consider a workup for these diagnoses if a typical workup rules out all usual causes of complications from an interscalene block.
John G. Skedros
Full Text Available This report describes a patient who had a series of daily interscalene nerve blocks to treat pain following a shoulder manipulation for postsurgical stiffness. She experienced acute respiratory compromise that persisted for many weeks. All typical and unusual causes of these symptoms were ruled out. Her treating pulmonologist theorized that the ipsilateral carotid body had been injured. However, it was subsequently determined that the constellation of symptoms and their prolonged duration were best explained by a poor stress response from Addison's disease coupled with exacerbation of early onset myasthenia gravis. This patient's case is not a typical reaction to interscalene nerve blocks, and thus preoperative testing would not be recommended for myasthenia gravis or Addison's disease without underlying suspicion. We describe this report to inform physicians to consider a workup for these diagnoses if a typical workup rules out all usual causes of complications from an interscalene block.
Brown, L.R.; Muhm, J.R.; Sheedy, P.F. II; Unni, K.K.; Bernatz, P.E.; Hermann, R.C. Jr.
In a 5 year study, 19 patients with myasthenia gravis were studied by computed tomography (CT) and underwent thymectomy. CT was accurate in detecting the nine true thymic masses but could not differentiate thymomas from nonthymomatous masses, including thymic cysts. No thymoma was found in a patient under 25 years of age. In one case, the 18 sec scanner could not differentiate a large gland from a thymoma. In eight cases, glands with histologic thymic hyperplasia and histologically normal thymus appeared to be similar and could not be differentiated by CT
Brown, L.R.; Muhm, J.R.; Sheedy, P.F. II; Unni, K.K.; Bernatz, P.E.; Hermann, R.C. Jr.
In a 5 year study, 19 patients with myasthenia gravis were studied by computed tomography (CT) and underwent thymectomy. CT was accurate in detecting the nine true thymic masses but could not differentiate thymomas from nonthymomatous masses, including thymic cysts. No thymoma was found in a patient under 25 years of age. In one case, the 18 sec scanner could not differentiate a large gland from a thymoma. In eight cases, glands with histologic thymic hyperplasia and histologically normal thymus appeared to be similar and could not be differentiated by CT.
Li, Yan; Tu, Zhidan; Qian, Shiguang; Fung, John J; Markowitz, Sanford D; Kusner, Linda L; Kaminski, Henry J; Lu, Lina; Lin, Feng
We recently demonstrated that hepatic stellate cells induce the differentiation of myeloid-derived suppressor cells (MDSCs) from myeloid progenitors. In this study, we found that adoptive transfer of these MDSCs effectively reversed disease progression in experimental autoimmune myasthenia gravis (EAMG), a T cell-dependent and B cell-mediated model for myasthenia gravis. In addition to ameliorated disease severity, MDSC-treated EAMG mice showed suppressed acetylcholine receptor (AChR)-specific T cell responses, decreased levels of serum anti-AChR IgGs, and reduced complement activation at the neuromuscular junctions. Incubating MDSCs with B cells activated by anti-IgM or anti-CD40 Abs inhibited the proliferation of these in vitro-activated B cells. Administering MDSCs into mice immunized with a T cell-independent Ag inhibited the Ag-specific Ab production in vivo. MDSCs directly inhibit B cells through multiple mechanisms, including PGE2, inducible NO synthase, and arginase. Interestingly, MDSC treatment in EAMG mice does not appear to significantly inhibit their immune response to a nonrelevant Ag, OVA. These results demonstrated that hepatic stellate cell-induced MDSCs concurrently suppress both T and B cell autoimmunity, leading to effective treatment of established EAMG, and that the MDSCs inhibit AChR-specific immune responses at least partially in an Ag-specific manner. These data suggest that MDSCs could be further developed as a novel approach to treating myasthenia gravis and, even more broadly, other diseases in which T and B cells are involved in pathogenesis. Copyright © 2014 by The American Association of Immunologists, Inc.
Hansen, Julie S; Danielsen, Ditte H; Somnier, Finn E
INTRODUCTION: In previous studies of myasthenia gravis (MG), increased mortality has been reported. The aim of this study was to estimate mortality in patients with acetylcholine receptor antibody-positive (AChR-Ab-seropositive) MG in a nationwide population-based, long-term follow-up study...
Vinge, Lotte; Jakobsen, Johannes; Pedersen, Asger Roer
INTRODUCTION: In patients with myasthenia gravis (MG), muscle strength is expected to decrease gradually during the day due to physical activities. METHODS: Isometric muscle strength at the shoulder, knee, and ankle was determined in 10 MG patients (MGFA class II-IV) who were receiving usual...
Full Text Available ObjectiveTo describe the characteristics of patients with amyotrophic lateral sclerosis (ALS and myasthenia gravis (MG overlap syndrome and explore the relationship between the two diseases.MethodsWe conducted a search of medical records at Peking Union Medical University Hospital from 1983 to 2015 for coexistence of ALS and MG and searched the PubMed database for all literature describing ALS and MG overlap syndrome published through December 2016. We analyzed the clinical and neurophysiological characteristics of patients by groups according to strict diagnostic criteria.ResultsWe presented 2 patients in our database with combined ALS and MG, and together with 25 cases reported in the literature, the patients were divided into 4 groups: 12 patients with MG followed by ALS, 8 patients with ALS followed by MG, 5 ALS patients with false-positive anti-acetylcholine receptor, and the other 2 ALS patients with only myasthenia symptoms. Most patients had limb onset ALS, and myasthenia symptoms mainly affected ocular and bulbar muscles. Clinical and neurophysiological characteristics were summarized.ConclusionThese findings support the conclusion that immunological mechanisms and alterations in the neuromuscular junction are related to ALS pathogenesis.
José Lamartine de Assis
Full Text Available Two pairs of siblings with myasthenia gravis, belonging to two different families, are reported. This is the only record of familial myasthenia during the past twenty years, in a total of 145 patients seen at the Neurological Clinic of the São Paulo Medical School. In spite of the fact that myasthenia gravis does not show hereditary characteristics, the peculiar features of the four cases justify the present report. The two pairs of siblings were born from non myasthenic nor consanguineous parents. The disease started at birth showing bilateral partial eyelid ptosis in all patients. The course of the illness has been favorable. There was no thymoma.Os autores registram dois pares de gêmeos com miastenia grave, pertencentes a duas famílias diferentes. Este é o único registro de miastenia familial durante os últimos 20 anos, num total de 145 pacientes examinados na Clínica Neurológica da FMUSP. Apesar do fato de a miastenia grave não ter características hereditárias, os aspectos peculiares dos quatro pacientes justificam o presente registro. Os dois pares de gêmeos nasceram de pais não miastênicos e sem consanguinidade. A doença iniciou-se no nascimento, evoluindo com ptose bilateral parcial da pálpebra superior precocemente em todos os pacientes. O curso da moléstia tem sido favorável. Não havia timoma.
Chigurupati, Keerthi; Gadhinglajkar, Shrinivas; Sreedhar, Rupa; Nair, Muraleedharan; Unnikrishnan, Madathipat; Pillai, Manjusha
To determine the criteria for postoperative mechanical ventilation after thymectomy in patients with Myasthenia Gravis. Retrospective study. Teritiary care centre. 77 Myasthenia gravis patients operated for thymectomy were studied. After obtaining clearance from Institutional ethics committee, medical records of 77 patients with MG, who were operated for thymectomy between January 2005 and December 2015 were reviewed in a retrospective manner. Perioperative variables collected from the patient records were demographic data, duration of the disease, Osserman and Genkin classification, Anti-acetylcholine antibody (AChR) positivity, preoperative daily dose of drug, history of preoperative myasthenic crisis, preoperative vital capacity, technique of anesthesia, drugs used for anesthesia, perioperative complications, and duration of postoperative mechanical ventilation. The patients were divided into two groups, group I and group II consisting of those who required postoperative ventilation for 300 minutes, respectively. The determinants of prolonged postoperative ventilation were studied. The requirement of mechanical ventilation was higher in patients with higher Osserman's grade of myasthenia gravis. Duration of the disease had no effect on the duration of mechanical ventilation in myasthenic patients post thymectomy (p = 0.89). The patients with a preoperative history of myasthenic crisis had a requirement for prolonged mechanical ventilation (p=0.03). Patients with preoperative vital capacity mechanical ventilation with p values mechanical ventilation (p=0.026). Preoperative dose of pyridostigmine and the choice of continuation or discontinuation of antcholinesterases on the day of surgery had no influence on the duration of mechanical ventilation (p value of 0.19 and 0.36 respectively). Epidural analgesia intra and postoperatively significantly reduced the requirement of mechanical ventilation (p=0.006). The predictors of postoperative ventilation in myasthenic
Vasil' ev, V.N.; Bel' chikova, N.S.; Kuksinskij, V.E. (Leningradskij Inst. Usovershenstvovaniya Vrachej (USSR))
Based on an analysis of X-ray, intraoperative and histological findings in 124 operated on patients (thymectomy) with myasthenia the authors describe potentialities of pneumomediastinography (PMG) (pheumomediastinotomography-PMTG) in the determination of its main variants (hyperplasia, involution, tumor). Clear knowledge of the variants of x-ray image of the normal anatomical structures of the anterior mediastinum and age peculiarities of the thymus for correct interpretation of pneumomediastinograms is necessary. The importance of selective phlebography of the thymus for differential diagnosis of thymomas and nodular indurations of the fatty tissue in the anterior mediastinum, thymomas and fatty involution of the thymus, residual thymus and zones of fibrous-adipose tissue in the mediastinum is stressed. Selective phlebography is a simple and safe method that adds to PMG (PMTG) potentialities in the evaluation of thymus evolution in myasthenia.
Coisy, Solène; Ebran, Jean-Marc; Milea, Dan
Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.
Leonardi, Matilde; Raggi, Alberto; Antozzi, Carlo; Confalonieri, Paolo; Maggi, Lorenzo; Cornelio, Ferdinando; Mantegazza, Renato
The objective of this study is to describe functional profiles of patients with myasthenia gravis (MG), and the relationships among symptoms, activities and environmental factors (EF), by using WHO's International Classification of Functioning Disability and Health (ICF). Patients were consecutively enrolled at the Besta Institute of Milan, Italy.…
Full Text Available Neonatal pustular eruption is a group of disorders characterized by various forms of pustulosis seen in first 4 weeks of life. Its presentation is often similar with some subtle differences, which can be further established by few simple laboratory aids, to arrive at a definite diagnosis. Given their ubiquitous presentation, it is sometimes difficult to differentiate among self-limiting, noninfectious, pustular dermatosis such as erythema toxicum neonatorum, transient neonatal pustular melanosis, miliaria pustulosa, etc., and potentially life threatening infections such as herpes simplex virus and varicella zoster virus infections. This review article tries to address the chronological, clinical, morphological, and histological differences among the various pustular eruptions in a newborn, in order to make it easier for a practicing dermatologist to diagnose and treat these similar looking but different entities of pustulation with a clear demarcation between the physiological benign pustular rashes and the infectious pustular lesions.
Singh, Paramveer; Idowu, Olakunle; Malik, Imrana; Nates, Joseph L
Magnesium is known to act at the neuromuscular junction by inhibiting the presynaptic release of acetylcholine and desensitizing the postsynaptic membrane. Because of these effects, magnesium has been postulated to potentiate neuromuscular weakness. We describe the case of a 62-year-old woman with myasthenia gravis and a metastatic thymoma who was admitted to our intensive care unit for management of a myasthenic crisis. The patient's neuromuscular weakness worsened in association with standard intravenous magnesium replacement, and the exacerbated respiratory failure necessitated intubation, mechanical ventilation, and an extended stay in the intensive care unit. The effect of magnesium replacement on myasthenia gravis patients has not been well documented, and we present this case to increase awareness and stimulate research. In addition, we discuss the relevant medical literature.
Soetje, G.; Brinkmann, G.; Striepling, E.; Engemann, R.
A 40-year old woman with an invasive thymoma and myasthenia gravis is described in this article. Chest-x-ray, CT and MRI of the mediastinum could not offer definite results on tumour malignancy. Radical surgical removal was the consequence. This revealed a tumour infiltration of the pleura and pericardium; hence an adjuvant irradiation must have been performed. Mestinon-treatment was afterwards gradually reduced. (orig.) [de
Marr, Celia M
The neonatal foal is in a transitional state from prenatal to postnatal circulation. Healthy newborn foals often have cardiac murmurs and dysrhythmias, which are usually transient and of little clinical significance. The neonatal foal is prone to infection and cardiac trauma. Echocardiography is the main tool used for valuation of the cardiovascular system. With prompt identification and appropriate action, dysrhythmias and other sequel to cardiac trauma can be corrected. With infection, the management and prognosis are driven by concurrent sepsis. Congenital disease represents an interesting diagnostic challenge for the neonatologist, but surgical correction is not appropriate for most equids. Copyright © 2015 Elsevier Inc. All rights reserved.
Leonardo H. Mendonça Oliveira
Full Text Available OBJECTIVE: A cross-sectional study of haptoglobin (Hp in myasthenia gravis (MG was designed, with the objective to identify its values and correlate them with different disease status. METHOD: 46 patients were enrolled in the study, all having disease severity established according to the quantitative myasthenia gravis strength scores (QMGSS. Based on the functional scale determined by Myasthenia Gravis Foundation of America (MGFA recommendations, patients were classified as having: complete stable remission (CSR; n=10; minimal manifestations-0 (MM0; n=6, minimal manifestations-1 (MM1; n=4; pharmacological remission (PR; n=6. Two other groups participated: thymomatous patients (T; n=10 and patients without imunosuppression or thymectomy, until the assessment for Hp (WIT; n=10. Hp dosage was done by immunonephelometry, blindly to clinical data. Student's t-test, Anova test and linear regression were employed for statistical analyses. RESULTS: Statistically significant differences occurred between CSR+MM0xWIT groups (86.62x157.57, pOBJECTIVO: Desenhou-se estudo transversal sobre a haptoglobina (Hp na miastenia grave (MG com o objetivo de identificar seus valores e correlacioná-los a diferentes condições na doença. MÉTODO: 46 pacientes foram incluídos, todos tendo a gravidade da doença estabelecida segundo escores internacionais (QMGSS. Os pacientes tiveram seu estado funcional determinado de acordo com a Myasthenia Gravis Foundation of América (MGFA e classificados em: remissão completa estável (CSR; n=10; mínima manifestação-0 (MM0; n=6, mínima manifestação-1 (MM1; n=4; remissão farmacológica (PR; n=6. Dois outros grupos participaram: pacientes timomatosos (T; n=10 e pacientes sem imunossupressão ou timectomia, até o momento da inclusão no estudo (WIT; n=10. A dosagem de Hp foi realizada por imunonefelometria, de modo cego quanto à clínica. As análises estatísticas incluíram o teste de Student, Anova e regressão linear
Pestronk, A.; Drachman, D.B.; Teoh, R.; Adams, R.N.
A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. ''Memory'' lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the ''memory'' cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar ''curative'' strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis
Vasil'ev, V.N.; Bel'chikova, N.S.; Kuksinskij, V.E.
Basing on an analysis of X-ray, intraoperative and histological findings in 124 operated on patients (thymectomy) with myasthenia the authors describe potentialities of pneumomediastinography (PMG) (pheumomediastinotomography-PMTG) in the determination of its main variants (hyperplasia, involUtion, tumor). Clear knowledge of the variants of x-ray image of the normal anatomical structures of the anterior mediastinum and age peculiarities of the thymus for correct interpretation of pneumomediastinograms is necessary. The importance of selective phlebography of the thymus for differential diagnosis of thymomas and nodular indurations of the fatty tissue in the anterior mediastinum, thymomas and fatty involution of the thymus, residual thymus and zones of fibrous-adipose tissue in the mediastinum is stressed. Selective phlebography is a simple and safe method that adds to PMG (PMTG) potentialities in the evaluation of thymus evolution in myasthenia
Thorvinger, B.; Lyttkens, K.; Samuelsson, L.
Sixteen consecutive patients with myasthenia gravis were examined by computed tomography (CT) before thymectomy. Surgical and histologic findings were compared with those obtained at CT. The results, like those of most other recent studies, indicate that CT is a reliable method for identifying thymoma. In all three patients with thymoma, and in five out of eight patients with hyperplasia, the lesion was observed at CT, giving an overall accuracy of 80%. Although tymic hyperplasia is a basically histological diagnosis an enlarged gland may give a correct diagnosis of this abnormality. (orig.)
Thorvinger, B.; Lyttkens, K.; Samuelsson, L.
Sixteen consecutive patients with myasthenia gravis were examined by computed tomography (CT) before thymectomy. Surgical and histologic findings were compared with those obtained at CT. The results, like those of most other recent studies, indicate that CT is a reliable method for identifying thymoma. In all three patients with thymoma, and in five out of eight patients with hyperplasia, the lesion was observed at CT, giving an overall accuracy of 80%. Although tymic hyperplasia is a basically histological diagnosis an enlarged gland may give a correct diagnosis of this abnormality.
Yan, Chong; Song, Jie; Pang, Song; Yi, Fangfang; Xi, Jianying; Zhou, Lei; Ding, Ding; Wang, Weifeng; Qiao, Kai; Zhao, Chongbo
Repetitive nerve stimulation (RNS) is a valuable diagnostic method for myasthenia gravis (MG). However, its association with clinical severity was scarcely studied. We reviewed medical records and retrospectively enrolled 121 generalized MG patients. Sensitivity of different muscles to RNS and clinical scoring systems was evaluated. RNS testing revealed facial muscles have the highest positive rate, followed by proximal muscles and distal muscles, with the palpebral portion of the orbicularis oculi muscle most sensitive. Amplitude decrement of compound muscle action potential (CMAP) in the palpebral portion of the orbicularis oculi muscle is related to quantitative myasthenia gravis (QMG) scores, MG-specific manual muscle testing (MMT) scores and myasthenia gravis-related activities of daily living (MG-ADL) scores. We suggest that RNS testing of the palpebral portion of the orbicularis oculi muscle is a potential assessment indicator in patients with generalized MG. Copyright © 2017 Elsevier Ltd. All rights reserved.
Almog, Yehoshua; Ben-David, Merav; Nemet, Arie Y
Myasthenia gravis may affect any of the six extra-ocular muscles, masquerading as any type of ocular motor pathology. The frequency of involvement of each muscle is not well established in the medical literature. This study was designed to determine whether a specific muscle or combination of muscles tends to be predominantly affected. This retrospective review included 30 patients with a clinical diagnosis of myasthenia gravis who had extra-ocular muscle involvement with diplopia at presentation. The diagnosis was confirmed by at least one of the following tests: Tensilon test, acetylcholine receptor antibodies, thymoma on chest CT scan, or suggestive electromyography. Frequency of involvement of each muscle in this cohort was inferior oblique 19 (63.3%), lateral rectus nine (30%), superior rectus four (13.3%), inferior rectus six (20%), medial rectus four (13.3%), and superior oblique three (10%). The inferior oblique was involved more often than any other muscle (pmyasthenia gravis can be difficult, because the disease may mimic every pupil-sparing pattern of ocular misalignment. In addition diplopia caused by paresis of the inferior oblique muscle is rarely encountered (other than as a part of oculomotor nerve palsy). Hence, when a patient presents with vertical diplopia resulting from an isolated inferior oblique palsy, myasthenic etiology should be highly suspected. Copyright © 2015 Elsevier Ltd. All rights reserved.
To measure the true prevalence of hearing impairment in neonates in Tafila, Jordan. This retrospective study was carried out at Prince Zeid Hospital, Taflia, Jordan through analysis of data of all births from January 2005 and January 2006. Transient evoked otoacoustic emissions (TEOAE) were measured via the application of echoprobe to both ears. There were two groups of births that were analysed statistically. Hearing impaired neonates were those with two fails or more in each ear. Normal ones were those with 3 pass or more. Of the 1788 babies in the study group, 1622 (90.7%) were enrolled in the study with 9.3% loss rate. 1512 babies were examined on the 2 day of birth, 2 of them had hearing impairment with a rate of 1.2/1000. 110 babies were screened on the day of discharge from the nursery, one of them with hearing defect with a rate of 5.9/1000. Thus, true prevalence of hearing impaiment or failure was 1.7/1000. We conclude that screening for hearing impairment in the neonatal period is easy, informative and the true prevalence of hearing impairment in Tafila is similar to that in different parts of the world. (author)
Luo, Jie; Lindstrom, Jon
Myasthenia gravis (MG) is an organ-specific autoimmune disease characterized by muscle fatigability. In most cases, it is mediated by autoantibodies targeting muscle nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction. Experimental autoimmune myasthenia gravis (EAMG) is an animal model for MG, which is usually induced by immunization with AChR purified from fish electric organ. Pathological autoantibodies to AChRs are directed at the extracellular surface, especially the main immunogenic region (MIR). Current treatments for MG can help many but not all patients. Antigen-specific immunosuppressive therapy for MG that specifically suppresses the autoimmune response without affecting the entire immune system and avoids side effects of general immunosuppression is currently unavailable. Early attempts at antigen-specific immunosuppression for EAMG using AChR extracellular domain sequences that form epitopes for pathological autoantibodies risked provoking autoimmunity rather than suppressing it. We discovered a novel approach to specific immunosuppression of EAMG with a therapeutic vaccine consisting of bacterially-expressed human AChR cytoplasmic domains, which has the potential to specifically suppress MG without danger of causing exacerbation. This approach prevents development of chronic EAMG when initiated immediately after the acute phase of EAMG, and rapidly reverses established chronic EAMG when started during the chronic phase of EAMG. Successfully treated rats exhibited long-term resistance to re-induction of EAMG. In this review we also discuss the current understanding of the mechanisms by which the therapy works. Vaccination with AChR cytoplasmic domains in adjuvant is promising as a safe, antigen-specific, potent, effective, rapidly acting, and long lasting approach to therapy of MG. Copyright © 2015 Elsevier Inc. All rights reserved.
Smid, Marcela C; Vladutiu, Catherine J; Dotters-Katz, Sarah K; Manuck, Tracy A; Boggess, Kim A; Stamilio, David M
Objective To estimate the association between maternal super obesity (body mass index [BMI] ≥ 50 kg/m(2)) and neonatal morbidity among neonates born via cesarean delivery (CD). Methods Retrospective cohort of singleton neonates delivered via CD ≥ 37 weeks in the Maternal-Fetal Medicine Unit Cesarean Registry. Maternal BMI at delivery was stratified as 18.5 to 29.9 kg/m(2), 30 to 39.9 kg/m(2), 40 to 49.9 kg/m(2), and ≥ 50 kg/m(2). Primary outcomes included acute (5-minute Apgar score neonatal injury, and/or transient tachypnea of the newborn) and severe (grade 3 or 4 intraventricular hemorrhage, necrotizing enterocolitis, seizure, respiratory distress syndrome, hypoxic ischemic encephalopathy, meconium aspiration, ventilator support ≥ 2 days, sepsis and/or neonatal death) neonatal morbidity. Odds of neonatal morbidity were estimated for each BMI category adjusting for clinical and operative characteristics. Results Of 41,262 maternal-neonatal dyads, 36% of women were nonobese, 49% had BMI of 30 to 39.9 kg/m(2), 12% had BMI of 40 to 49.9 kg/m(2), and 3% were super obese. Compared with nonobese women, super obese women had twofold odds of acute (5 vs. 10%; adjusted odds ratio [aOR]: 1.81, 95% confidence interval [CI]: 1.59-2.73) and severe (3 vs. 6%; aOR: 2.08; 95% CI: 1.59-2.73) neonatal morbidity. Conclusion Among term infants delivered via CD, maternal super obesity is associated with increased risk of neonatal morbidity. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Ou, C Y; Ran, H; Qiu, L; Huang, Z D; Lin, Z Z; Deng, J; Liu, W B
Objective: To investigate the clinical features of the Pre-Crisis State and analyze the correlated risk factors of Pre-Crisis State of myasthenia crisis. Methods: We included 93 patients with myasthenia gravis (MG) who experienced 127 times Pre-Crisis State between October 2007 and July 2016. Those patients were hospitalized in the MG specialize center, Department of Neurological Science, first Affiliated Hospital of Sun Yat-sen University. The information of the general situation, the clinical manifestations and the blood gas analysis in those patients were collected using our innovated clinical research form. Statistic methods were applied including descriptive analysis, univariate logistic analysis, multivariate correlation logistic analysis, etc. Results: (1)The typical features of MG Pre-Crisis State included: dyspnea (127 times, 100% not requiring intubation or non-invasive ventilation), bulbar-muscle weakness (121 times, 95.28%), the increased blood partial pressure of carbon dioxide (PCO(2)) (94 times, 85.45%), expectoration weakness (99 times, 77.95%), sleep disorders (107 times, 84.25%) and the infection (99 times, 77.95%). The occurrence of dyspnea in combination with bulbar-muscle weakness ( P =0.002) or the increased blood PCO(2) ( P =0.042) often indicated the tendency of crisis. (2) The MG symptoms which were proportion to the occurrence of crisis includes: bulbar-muscle weakness ( P =0.028), fever ( P =0.028), malnutrition ( P =0.066), complications ( P =0.071), excess oropharyngeal secretions ( P =0.005) and the increased blood PCO(2) ( P =0.007). The perioperative period of thymectomy would not increase the risk of crisis. Conclusions: Dyspnea indicates the occurrence of the Pre-Crisis State of MG. In order to significantly reduce the morbidity of myasthenia crisis, the bulbar-muscle weakness, the increased blood PCO(2), expectoration weakness, sleep disorders, infection & fever and excess oropharyngeal secretions should be treated timely.
Full Text Available Myasthenia gravis is an autoimmune disorder in which antibodies have been shown to form against the nicotinic acetylcholine nicotinic postsynaptic receptors located at the neuromuscular junction. "Warming yang and invigorating qi" acupuncture treatment has been shown to reduce serum inflammatory cytokine expression and increase transforming growth factor beta expression in rats with experimental autoimmune myasthenia gravis. However, few studies have addressed the effects of this type of acupuncture on the acetylcholine receptors at the neuromuscular junction. Here, we used confocal laser scanning microscopy to examine the area and density of immunoreactivity for an antibody to the nicotinic acetylcholine receptor at the neuromuscular junction in the phrenic nerve of rats with experimental autoimmune myasthenia gravis following "warming yang and invigorating qi" acupuncture therapy. Needles were inserted at acupressure points Shousanli (LI10, Zusanli (ST36, Pishu (BL20, and Shenshu (BL23 once daily for 7 consecutive days. The treatment was repeated after 1 day of rest. We found that area and the integrated optical density of the immunoreactivity for the acetylcholine receptor at the neuromuscular junction of the phrenic nerve was significantly increased following acupuncture treatment. This outcome of the acupuncture therapy was similar to that of the cholinesterase inhibitor pyridostigmine bromide. These findings suggest that "warming yang and invigorating qi" acupuncture treatment increases acetylcholine receptor expression at the neuromuscular junction in a rat model of autoimmune myasthenia gravis.
Full Text Available Introduction: Progressive outer retinal necrosis (PORN is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV and responsible for severe visual loss. Case Report: A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion: VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.
Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik
Abstract Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis. PMID:25915571
Full Text Available Background: Respiratory failure and crisis is one of major complications of thymectomy in myasthenia gravis patients. There are different medication regimes for preparing these patients for surgery and reducing post-operative side effects. The goal of this study is to compare respiratory complications of oral vs. Parenteral preoperative administration of anticholinesterase agents for thymectomy in myasthenia gravis patients. Methods: This randomized controlled trial included 101 patients in class IIA or IIB of myasthenia gravis according to the Osserman classification system. The control group fasted for eight hours before surgery and oral anticholines-terase agents were replaced with parenteral ones. The case group also fasted for 8 hours before surgery, but pyridostigmine was continued at its usual dose until the time of operation and the last dose was given to patients with a small amount of water in the operating room on the operating bed. Results: There was no statistically meaningful difference between the two groups in terms of age, sex and pathologic findings. In comparison, the mean hospital stay for the case group was 3.98 days and 6.34 for the control group (p value = 0.003. There were eight cases of respiratory crisis or failure (16% in the control group but only 1 case (2% was observed in case group (p value = 0.014. Only one patient in the case group required re-intubation after the surgery; however, six patients in control group were re-intubated (p value = 0.053. Plasmapheresis was required for five patients in the control group and one patient in the case group (p value = 0.098. Tracheostomy was performed on two patients in the control group to accommodate prolonged intubation, but none of the case group required this procedure. Conclusion: This study shows that continuing oral anticholinesterase agents up to the time of operation, with the last dose at the operative theater, lowers the incidence of post-operative myasthenia
Full Text Available Introduction. There is carried out reconstruction of the past in the field of integrated discoveries of well-known scientist I.I. Mechnikov for research of aspects of phagocytic function of immune cells and infectious factors in etiology and pathogenesis of progressing myasthenia. There are analyzed the leading factors which have generated scientific outlook and integrated analytical methodology of knowledge of I.I. Mechnikov – the native of the Kharkov province, the graduate student of the Kharkov Imperial University of 1864, the Nobel prize winner of 1908 for creation of the theory of phagocytosis and the author of set of works in the field of microbiology, immunology and virology. Material & methods. The work studied the mechanisms of disorder of various stages of barrier phagocytic function of neutrophils and frequency of occurrence and various degree of expression of virus persistence at patients with myasthenia is determined. Phagocytosis disturbance leads to uncontrollable development of infections at myasthenia. Advance of muscular delicacy and morph-functional disturbances in thymus, obviously, depend on the individual mechanisms which affect various stages of immune disbalance. The whole century has passed from the moment of creation of the phagocytic theory. For this time all stages of this process have been studied, methodical approaches are developed for an estimation of specific features of this phenomenon, from light microscopy to flowing cytofluorometry. Possibilities of light microscopy allow to visualize the stages of phagocytosis from chemotaxis and adhesions to completeness of digestion by neutrophils in dynamics. And Nitro Blue Tetrazolium Reduction Test (NBTR is used for an estimation of enzymatic activity of phagocytes for initiation of formation of active forms of oxygen at the phagosoma formation stage. The given method allows to investigate stages of oxygen-dependent metabolism of neutrophils. Along with these methods
S. A. Perepelitsa
Full Text Available Objective: to study the production of surfactant apoprotein D in preterm neonates with acute respiratory distress syndrome (ARDS during artificial ventilation (AV. Subjects and methods. The paper presents the results of studying the production of surfactant protein D (SP-D in various biological fluids in 44 preterm neonates. Two groups of newborn infants were identified according to the clinical manifestations of ARDS. The study group comprised 25 infants with the severe course of the disease, in this connection the preventive administration of the exogenous surfactant Curosurf and AV were made in all the neonates at birth. The control group included 19 preterm babies without signs of ARDS. Results. The study has demonstrated that in parturients and preterm neonatal infants, surfactant apoprotein D is detectable in various biological fluids: amniotic fluid, the gastric aspirate obtained just after birth, residual umbilical cord blood, serum following 8 hours of birth, and bronchoalveolar fluid. Despite the low gestational age of the neonates, the lung surfactant system is able to produce SP-D, as evidenced by its high content in the amniotic fluid and residual umbilical cord blood of preterm neonates. The production of apoprotein D in preterm neonates considerably reduces in the next few hours after birth. Conclusion. The findings suggest that fetal tissues generate SP-D, which improves pulmonary gas exchange in preterm neonates in the first hours after birth and that alveolar-capillary membrane dysfunctions are transient in the neonates on AV. Key words: preterm neonates, acute respiratory distress syndrome, surfactant, surfactant apoprotein D.
Avidan, Nili; Le Panse, Rozen; Harbo, Hanne F
OBJECTIVE: To identify novel genetic loci that predispose to early-onset myasthenia gravis (EOMG) applying a two-stage association study, exploration, and replication strategy. METHODS: Thirty-four loci and one confirmation loci, human leukocyte antigen (HLA)-DRA, were selected as candidate genes...
Pestronk, A.; Drachman, D.B.; Teoh, R.; Adams, R.N.
A therapeutic strategy was designed to eliminate the humoral immune response to acetylcholine receptor (AChR) in ongoing experimental autoimmune myasthenia gravis (EAMG). Rats with EAMG were treated with a protocol consisting of three components: (1) A single high dose of cyclophosphamide (200 mg/kg) was used to produce a rapid and sustained fall in the anti-AChR antibody levels by preferential destruction of antibody-producing B-lymphocytes. ''Memory'' lymphocytes were not eliminated by cyclophosphamide. (2) Irradiation (600 rads) was used to eliminate the ''memory'' cells. It eliminated the anamnestic response to a challenge with the antigen AChR. (3) Bone marrow transplantation was used to repopulate the hematopoietic system after the otherwise lethal dose of cyclophosphamide. We used bone marrow from syngeneic rats with active EAMG to simulate an autologous transplant. Rats with EAMG treated with this combined protocol showed a prompt and sustained fall in the anti-AChR antibody levels and had no anamnestic response to a challenge with AChR. Thus, an affected animal's own marrow could be stored and used later for repopulation after cyclophosphamide-irradiation treatment. This treatment eliminates the animal's ongoing immune responses and reconstitutes the immune system in its original state. The success of this approach suggests that, if their safety could be established, similar ''curative'' strategies might be developed for the treatment of patients with severe antibody-mediated autoimmune disorders, such as myasthenia gravis.
Korhonen, Topi; Hänninen, Sandra L; Tavi, Pasi
The neonatal rat ventricular myocyte culture is one of the most popular experimental cardiac cell models. To our knowledge, the excitation-contraction coupling (ECC) of these cells, i.e., the process linking the electrical activity to the cytosolic Ca2+ transient and contraction, has not been previously analyzed, nor has it been presented as a complete system in detail. Neonatal cardiomyocytes are in the postnatal developmental stage, and therefore, the features of their ECC differ vastly from those of adult ventricular myocytes. We present the first complete analysis of ECC in these cells by characterizing experimentally the action potential and calcium signaling and developing the first mathematical model of ECC in neonatal cardiomyocytes that we know of. We show that in comparison to adult cardiomyocytes, neonatal cardiomyocytes have long action potentials, heterogeneous cytosolic Ca2+ signals, weaker sarcoplasmic reticulum Ca2+ handling, and stronger sarcolemmal Ca2+ handling, with a significant contribution by the Na+/Ca2+ exchanger. The developed model reproduces faithfully the ECC of rat neonatal cardiomyocytes with a novel description of spatial cytosolic [Ca2+] signals. Simulations also demonstrate how an increase in the cell size (hypertrophy) affects the ECC in neonatal cardiomyocytes. This model of ECC in developing cardiomyocytes provides a platform for developing future models of cardiomyocytes at different developmental stages.
Full Text Available Renato Mantegazza, Silvia Bonanno, Giorgia Camera, Carlo AntozziDepartment of Neuromuscular Diseases and Neuroimmunology, Fondazione Istituto Neurologico Carlo Besta, Milan, ItalyAbstract: Myasthenia gravis (MG is an autoimmmune disease in which autoantibodies to different antigens of the neuromuscular junction cause the typical weakness and fatigability. Treatment includes anticholinesterase drugs, immunosuppression, immunomodulation, and thymectomy. The autoimmune response is maintained under control by corticosteroids frequently associated with immunosuppressive drugs, with improvement in the majority of patients. In case of acute exacerbations with bulbar symptoms or repeated relapses, modulation of autoantibody activity by plasmapheresis or intravenous immunoglobulins provides rapid improvement. Recently, techniques removing only circulating immunoglobulins have been developed for the chronic management of treatment-resistant patients. The rationale for thymectomy relies on the central role of the thymus. Despite the lack of controlled studies, thymectomy is recommended as an option to improve the clinical outcome or promote complete remission. New videothoracoscopic techniques have been developed to offer the maximal surgical approach with the minimal invasiveness and hence patient tolerability. The use of biological drugs such as anti-CD20 antibodies is still limited but promising. Studies performed in the animal model of MG demonstrated that several more selective or antigen-specific approaches, ranging from mucosal tolerization to inhibition of complement activity or cellular therapy, might be feasible. Investigation of the transfer of these therapeutic approaches to the human disease will be the challenge for the future.Keywords: myasthenia gravis, therapy, immunosuppression, thymectomy, plasmapheresis
Jordan, Berit; Schweden, Tabea L K; Mehl, Theresa; Menge, Uwe; Zierz, Stephan
Cognitive fatigue has frequently been reported in myasthenia gravis (MG). However, objective assessment of cognitive fatigability has never been evaluated. Thirty-three MG patients with stable generalized disease and 17 healthy controls underwent a test battery including repeated testing of attention and concentration (d2-R) and Paced Auditory Serial Addition Test. Fatigability was based on calculation of linear trend (LT) reflecting dynamic performance within subsequent constant time intervals. Additionally, fatigue questionnaires were used. MG patients showed a negative LT in second d2-R testing, indicating cognitive fatigability. This finding significantly differed from stable cognitive performance in controls (P fatigue was significantly higher in MG patients compared with controls (P fatigue is not correlated with objective findings. Muscle Nerve 56: 449-457, 2017. © 2016 Wiley Periodicals, Inc.
Kaul, P P; Srivastava, R; Srivastava, S P; Kamboj, M; Chand, S
Transient complications of pregnancy (anemia, toxemia, proteinuria, arterial hypertension and hyperemesis) were studied in pregnant women from the general population reporting to local hospitals. Comparison of blood lead levels (PbB) was made between women with normal pregnancies and those with complications. Significantly higher PbB were found in women with pregnancy complications as compared to those with normal pregnancies. Increments in the PbB levels were accompanied by statistically significant decrements in neonate birthweights. Complications of pregnancy may be induced by higher PbB and may also compound the adverse effects of decrements of neonate birthweights
Lennon, V A; Lambert, E H; Leiby, K R; Okarma, T B; Talib, S
A synthetic gene encoding the 210 N-terminal residues of the alpha-subunit of the nicotinic acetylcholine receptor (AChR) of human skeletal muscle was cloned into an inducible expression plasmid to produce a fusion protein in high yield in Escherichia coli. Like native human AChR, the recombinant human alpha 1-210 protein induced AChR-binding, AChR-modulating, and AChR-blocking autoantibodies in rats when injected once intradermally as an emulsion in CFA, with Bordetella pertussis vaccine as supplementary adjuvant. The minimum dose of recombinant protein required to induce biochemical signs of experimental autoimmune myasthenia gravis (EAMG) with 100% incidence was 2.2 micrograms. With 6.6 to 22 micrograms, serum levels of autoantibodies were persistent, and clinically apparent EAMG lasted more than a month. Clinical, electrophysiological, and biochemical indices of EAMG induced by doses of 66 micrograms or more were more uniformly severe and persistent, with 33% fatality. Rats receiving a control extract of E. coli containing plasmid without the alpha 1-210 codon insert, with adjuvants, did not develop autoantibodies or signs of EAMG. This highly reproducible new model of EAMG induced by a recombinant human autoantigen should be valuable for testing Ag-specific immunotherapeutic strategies that might be applicable to treating acquired myasthenia gravis in humans.
William D. Phillips
Full Text Available Myasthenia gravis is an autoimmune disease of the neuromuscular junction (NMJ caused by antibodies that attack components of the postsynaptic membrane, impair neuromuscular transmission, and lead to weakness and fatigue of skeletal muscle. This can be generalised or localised to certain muscle groups, and involvement of the bulbar and respiratory muscles can be life threatening. The pathogenesis of myasthenia gravis depends upon the target and isotype of the autoantibodies. Most cases are caused by immunoglobulin (IgG1 and IgG3 antibodies to the acetylcholine receptor (AChR. They produce complement-mediated damage and increase the rate of AChR turnover, both mechanisms causing loss of AChR from the postsynaptic membrane. The thymus gland is involved in many patients, and there are experimental and genetic approaches to understand the failure of immune tolerance to the AChR. In a proportion of those patients without AChR antibodies, antibodies to muscle-specific kinase (MuSK, or related proteins such as agrin and low-density lipoprotein receptor-related protein 4 (LRP4, are present. MuSK antibodies are predominantly IgG4 and cause disassembly of the neuromuscular junction by disrupting the physiological function of MuSK in synapse maintenance and adaptation. Here we discuss how knowledge of neuromuscular junction structure and function has fed into understanding the mechanisms of AChR and MuSK antibodies. Myasthenia gravis remains a paradigm for autoantibody-mediated conditions and these observations show how much there is still to learn about synaptic function and pathological mechanisms.
Topiol Emmanuelle S
Full Text Available Abstract Neonatal diabetes mellitus (NDM is a rare metabolic disorder, affecting approximately 1 in 500,000 live births. The management of NDM is challenging, as the benefits of controlling hyperglycemia must be balanced with the risks of iatrogenic hypoglycemia. NDM occurs in both permanent and transient forms, which have been genetically and phenotypically well characterized. Herein, we present the previously unreported combination of transient NDM (TNDM and congenital diaphragmatic hernia (CDH. In addition to reviewing the management and genetics of NDM we discuss the potential for overlapping genetic or embryologic abnormalities to explain the concurrence of CDH and NDM.
Fernández-López, David; Faustino, Joel; Klibanov, Alexander L.; Derugin, Nikita; Blanchard, Elodie; Simon, Franziska; Leib, Stephen L.; Vexler, Zinaida S.
Perinatal stroke leads to significant morbidity and long-term neurological and cognitive deficits. The pathophysiological mechanisms of brain damage depend on brain maturation at the time of stroke. To understand whether microglial cells limit injury after neonatal stroke by preserving neurovascular integrity, we subjected postnatal day 7 (P7) rats depleted of microglial cells, rats with inhibited microglial TGFbr2/ALK5 signaling, and corresponding controls, to transient middle cerebral arter...
Andersen, Jintana B; Gilhus, Nils Erik; Sanders, Donald B
Information from myasthenia gravis (MG) patients treated and evaluated for at least 2 years between 1980 and 2014 was reviewed to assess the effect of demographics, antibody status and titer, thymus histology, and clinical severity on outcome after 2, 5, and 10 years of treatment. Among 268 patients, 74% had acetylcholine receptor antibodies, 5% had muscle specific tyrosine kinase-antibodies, and 22% had neither. Optimal outcome was achieved by 64% of patients at 2 years of follow-up, 73% at 5 years, and 75% after 10 years. Optimal outcome was achieved more often in patients with late onset, in those who had thymectomy, and in those with ocular-only disease at maximum severity. The only consistent independent predictor of optimal outcome was onset after age 50 years on multivariate analysis. Prognosis is favorable for the majority of MG patients, regardless of age, maximum disease severity, or antibody status. Muscle Nerve, 2016 Muscle Nerve 54: 1041-1049, 2016. © 2016 Wiley Periodicals, Inc.
Kanike, Neelakanta; Davis, Ajuah
Transient congenital hypothyroidism (CH) refers to a temporary deficiency of thyroid hormone identified after birth, with low thyroxine (T4) and elevated thyrotropin (TSH), which later recovers to improved thyroxine production, typically in first few months of infancy. Approximately 17% to 40% of children diagnosed with CH by newborn screening (NBS) programs were later determined to have transient hypothyroidism. Causes of transient CH are prematurity, iodine deficiency, maternal thyrotropin receptor blocking antibodies, maternal intake of anti-thyroid drugs, maternal or neonatal iodine exposure, loss of function mutations and hepatic hemangiomas. The classic clinical symptoms and signs of CH are usually absent immediately after birth in vast majority of infants due to temporary protection from maternal thyroxine. NBS has been largely successful in preventing intellectual disability by early detection of CH by performing thyroid function tests in infants with abnormal screening results. In this review we present the evidence for decision making regarding treatment vs. withholding treatment in infants with transient CH and present a rational approach to identifying transient CH based on American Academy of Pediatrics (AAP) recommendation. PMID:29184815
Cleary, Ryan T; Sun, Hongyu; Huynh, Thanhthao; Manning, Simon M; Li, Yijun; Rotenberg, Alexander; Talos, Delia M; Kahle, Kristopher T; Jackson, Michele; Rakhade, Sanjay N; Berry, Gerard T; Berry, Gerard; Jensen, Frances E
Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+)-K(+)-2 Cl(-) cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.
Komasawa, Nobuyasu; Ueki, Ryusuke; Tomita, Yukihiko; Kaminoh, Yoshiroh; Tashiro, Chikara
We report a case of awake intubation utilizing Pentax-AWS Airwayscope in semi-sitting position. A 74-year-old man with myasthenia gravis and cervical disc hernia was scheduled for distal gastrectomy under general anesthesia. He could not move his head due to severe cervical disc hernia and also could not sufficiently breathe due to the fatigue of respiratory muscles by myasthenia gravis in supine position. With fentanyl bolus administration and lidocaine spray for laryngotracheal anesthesia, we performed awake intubation in semi-sitting position with AWS from cranial side. The patient did not buck during intubation and no hemodynamic change was observed.
Lichiardopol, Corina; Herlea, V; Ioan, Virginia; Tomulescu, V; Mixich, F
Both hypergonadotropic hypogonadism and myasthenia gravis can be parts of type II autoimmune polyendocrine syndrome and association between the two disorders has been reported in few cases. A 14 year old male patient with a personal history of bilateral cryptorchidism and ptosis was referred for delayed puberty. Clinical examination revealed eunuchoid habitus, small, soft testes, gynecomastia, ptosis, a myasthenic deficit score of 22.5 points and an IQ of 84 points. Decreased testosterone (0.064 ng/mL) and elevated LH (64.5 mUI/mL) were consistent with hypergonadotropic hypogonadism and karyotype was normal: 46,XY. Thyroid function, haematologic evaluation, BUN, electrolytes, and glycemia were in the normal range. Therapy consisted of anticholinesterase inhibitors, immunosuppressants, corticotherapy, testosterone; thoracoscopic thymectomy was performed showing thymic lymphoid hyperplasia on histopathologic examination. Myasthenic score improved (12.5 points), progressive virilization occurred, and a year later the patient presented with cushingoid features and obesity.
Enacán, Rosa E; Masnata, María E; Belforte, Fiorella; Papendieck, Patricia; Olcese, María C; Siffo, Sofía; Gruñeiro-Papendieck, Laura; Targovnik, Héctor; Rivolta, Carina M; Chiesa, Ana E
Congenital hypothyroidism affects 1:2000-3000 newborns detected by neonatal screening programs. Dual oxidases, DUOX1 and 2, generate hydrogen peroxide needed for the thyroid hormone synthesis. Hipotiroidismo congénito transitorio por defectos bialélicos del gen DUOX2. Dos casos clínicos Transient congenital hypothyroidism due to biallelic defects of DUOX2 gene. Two clinical cases Mutations in the DUOX2 gene have been described in transient and permanent congenital hypothyroidism. Two brothers with congenital hypothyroidism detected by neonatal screening with eutopic gland and elevated thyroglobulin are described. They were treated with levothyroxine until it could be suspended in both during childhood, assuming the picture as transient. Organification disorder was confirmed. Both patients were compounds heterozygous for a mutation in exon 9 of the paternal allele (c.1057_1058delTT, p.F353PfsX36 or p.F353fsX388) and in exon 11 of the maternal allele (c.1271T > G, p.Y425X) of DUOX2 gene. Our finding confirms that the magnitude of the defect of DUOX2 is not related to the number of inactivated alleles, suggesting compensatory mechanisms in the peroxide supply. Sociedad Argentina de Pediatría.
Hong, Yu; Xie, Yanchen; Hao, Hong-Jun; Sun, Ren-Cheng
Myasthenia gravis (MG) is a prototypic autoimmune disease with overt clinical and immunological heterogeneity. The data of MG is far from individually precise now, partially due to the rarity and heterogeneity of this disease. In this review, we provide the basic insights of MG data precision, including onset age, presenting symptoms, generalization, thymus status, pathogenic autoantibodies, muscle involvement, severity and response to treatment based on references and our previous studies. Subgroups and quantitative traits of MG are discussed in the sense of data precision. The role of disease registries and scientific bases of precise analysis are also discussed to ensure better collection and analysis of MG data. PMID:27127759
Zahid, Imran; Sharif, Sumera; Routledge, Tom; Scarci, Marco
A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was how video-assisted thoracoscopic surgery (VATS) compares to median sternotomy in the surgical management of patients with myasthenia gravis (MG)? Overall 74 papers were found using the reported search, of which 15 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results are tabulated. We conclude that VATS produces equivalent postoperative mortality and complete stable remission (CSR) rates, with superior results in terms of hospital stay, operative blood loss and patient satisfaction at the expense of a doubling of operative time. Six studies comparing VATS and transsternal sternotomy in non-thymomatous myasthenia gravis (NTMG) patients found VATS to have lower operative blood loss (73.8±70.7 vs. 155.3±91.7 ml; P0.05). One study comparing video-assisted thoracoscopic extended thymectomy to transsternal thymectomy in only thymoma-associated myasthenia gravis (T-MG) patients found equivalent CSR (11.3 vs. 8.7%, P=0.1090) at six-year follow-up. Thymoma recurrence rate (9.64%) was not significantly different (P=0.1523) between the two groups. Eight studies comparing VATS and transsternal approach in mixed T-MG and NTMG patients found a lower hospital stay (1.9±2.6 vs. 4.6±4.2 days, P<0.001), reduced need for postoperative medication (76.5 vs. 35.7%, P=0.022), lower intensive care unit stay (1.5 vs. 3.2 days, P=0.018), greater symptom improvement (100 vs. 77.9%, P=0.019) and better cosmetic satisfaction (100 vs. 83, P=0.042) with VATS. In concordance with NTMG and T-MG alone patient groups, VATS and transsternal methods had equivalent complication rates (23 vs. 19%, P=0.765) with no mortalities in either group. Even though VATS has a longer operative time (268±51 vs. 177±92 min, P<0.05), its improved cosmesis, reduced need
Full Text Available Objective To analyze the clinical characteristics, drug efficacy and prognosis of patients with myasthenia gravis (MG associated with other autoimmune diseases. Methods Eighty-three MG patients were divided into 2 groups. One group included MG patients with autoimmune diseases (AIDMG, N = 24, and the other included MG patients without autoimmune diseases (NAIDMG, N = 59. Firstly, clinical features such as sex, age of onset, initial symptoms and thymus abnormalities were compared between patients with AIDMG and NAIDMG. Secondly, effect of different therapies, including pyridostigmine, corticosteroids, immunoglobulin, immunosuppressants and thymectomy was compared between 2 groups. Finally, prognosis including relapse rate and recurrence time during the first 2 years after MG onset was compared. Whether and when ocular myasthenia gravis (OMG progressing to general myasthenia gravis (GMG and the first onset of GMG symptoms during the first 2 years were also compared between 2 groups. Results The difference of gender predominance (χ2 = 8.467, P = 0.004, ptosis affecting left or right or both sides (χ2 = 9.830, P = 0.007 and disease course within 2 years after onset (χ2 = 15.255, P = 0.001 between AIDMG group and NAIDMG group were statistically significant. Other clinical features such as age of onset (χ2 = 1.728, P = 0.228, initial symptoms (χ2 = 0.252, P = 0.791, thymus abnormalities (χ2 = 3.200, P = 0.202 were not significantly different between 2 groups. Differences of therapeutical effect such as pyridostigmine (χ2 = 0.411, P = 0.395, corticosteroids (χ2 = 0.156, P = 0.513, immunoglobulin (χ2 = 0.359, P = 0.462, immunosuppressants (χ2 = 0.081, P = 0.526 and thymectomy (χ2 = 0.337, P = 0.391 between 2 groups were not statistically significant. The ratio of OMG progressing to GMG (χ2 = 1.826, P = 0.148, time of progressing (Fisher's exact test: P = 0.639, first onset symptom (Fisher's exact test: P = 0.196 and recurrence
... Home > Complications & Loss > Loss & grief > Neonatal death Neonatal death E-mail to a friend Please fill in ... cope with your baby’s death. What is neonatal death? Neonatal death is when a baby dies in ...
Ryan T Cleary
Full Text Available Neonatal seizures can be refractory to conventional anticonvulsants, and this may in part be due to a developmental increase in expression of the neuronal Na(+-K(+-2 Cl(- cotransporter, NKCC1, and consequent paradoxical excitatory actions of GABAA receptors in the perinatal period. The most common cause of neonatal seizures is hypoxic encephalopathy, and here we show in an established model of neonatal hypoxia-induced seizures that the NKCC1 inhibitor, bumetanide, in combination with phenobarbital is significantly more effective than phenobarbital alone. A sensitive mass spectrometry assay revealed that bumetanide concentrations in serum and brain were dose-dependent, and the expression of NKCC1 protein transiently increased in cortex and hippocampus after hypoxic seizures. Importantly, the low doses of phenobarbital and bumetanide used in the study did not increase constitutive apoptosis, alone or in combination. Perforated patch clamp recordings from ex vivo hippocampal slices removed following seizures revealed that phenobarbital and bumetanide largely reversed seizure-induced changes in EGABA. Taken together, these data provide preclinical support for clinical trials of bumetanide in human neonates at risk for hypoxic encephalopathy and seizures.
Paik, Julie J.; Corse, Andrea M.; Mammen, Andrew L.
Objective Myositis and myasthenia gravis (MG) are both autoimmune disorders presenting with muscle weakness. Rarely, they occur simultaneously in the same patient. Since the management of myasthenia gravis differs from that of myositis, it is important to recognize when patients have both diseases. We reviewed the cases of 6 patients with both myositis and MG to identify clinical features that suggest the possibility of co-existing MG in myositis patients. Methods We identified 6 patients with dermatomyositis or polymyositis and MG. We reviewed their medical records to assess their clinical presentations, laboratory findings, and electrophysiological features. Results All 6 patients had definite dermatomyositis or polymyositis by the criteria of Bohan and Peter as well as electrophysiologic and/or serologic confirmation of MG. Among overlap patients, 5/6 (83%) had bulbar weakness, 2/6 (33%) had ptosis, and 1/6 (17%) had diplopia. Fatigable weakness was noted by 5/6 (83%) patients. Treatment with pyridostigmine improved symptoms in 5/6 (83%). High dose steroids were associated with worsening weakness in 2/6 (33%) patients. Conclusions Prominent bulbar symptoms, ptosis, diplopia, and fatigable weakness should suggest the possibility of MG in patients with myositis. A suspicion of MG may be confirmed through appropriate electrophysiologic and laboratory testing. In those with myositis-MG overlap, high dose steroids may exacerbate symptoms and pryidostigmine may play an important therapeutic role. PMID:24412588
Yamada, Chisa; Teener, James W; Davenport, Robertson D; Cooling, Laura
Anti-muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasthenic crisis. We report here successful management of three MuSK MG patients using maintenance therapeutic plasma exchange (TPE) treatment for up to 4.5 years. The study was a 5-year retrospective review of all MG patients treated with TPE between 2008 and 2013 at University of Michigan. Inclusion criteria of MuSK MG were positive for anti-MuSK antibodies and a diagnosis of MuSK MG by staff neurologists. Patient data included age, gender, diagnostic testing results, medications, and the dates and response to TPE treatments. A total of 153 MG patients underwent at least one course of TPE between 2008 and 2013. A total of 12 patients (7.8%) were positive for anti-MuSK antibodies. Patients were predominantly female (83.3%) and a median age of onset was 46-years old. Three MuSK MG patients were successfully managed with maintenance TPE. Maintenance TPE may be an effective option for MuSK MG patients. The key of successful maintenance treatment at our institution has been to tailor the TPE frequency for each individual, and to modify the treatment interval in conjunction with medical management. © 2014 Wiley Periodicals, Inc.
Full Text Available Autoimmune diseases (AIDs are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG. In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed.
Lopomo, Angela; Berrih-Aknin, Sonia
Autoimmune diseases (AIDs) are the result of specific immune responses directed against structures of the self. In normal conditions, the molecules recognized as “self” are tolerated by immune system, but when the self-tolerance is lost, the immune system could react against molecules from the body, causing the loss of self-tolerance, and subsequently the onset of AID that differs for organ target and etiology. Autoimmune thyroid disease (ATD) is caused by the development of autoimmunity against thyroid antigens and comprises Hashimoto’s thyroiditis and Graves disease. They are frequently associated with other organ or non-organ specific AIDs, such as myasthenia gravis (MG). In fact, ATD seems to be the most associated pathology to MG. The etiology of both diseases is multifactorial and it is due to genetic and environmental factors, and each of them has specific characteristics. The two pathologies show many commonalities, such as the organ-specificity with a clear pathogenic effect of antibodies, the pathological mechanisms, such as deregulation of the immune system and the implication of the genetic predisposition. They also show some differences, such as the mode of action of the antibodies and therapies. In this review that focuses on ATD and MG, the common features and the differences between the two diseases are discussed. PMID:28751878
Swischuk, L.E.; Hayden, K.; Richardson, J.
Eight newborn infants with opaque right lungs were examined. Clinically, the main problem associated with the opaque right lung is mild respiratory distress, and radiographyically, the findings consist of (a) a totally opaque right lung, (b) a semiopaque right lung, or (c) an opaque right upper lobe only. These findings are usually interpreted as representing pneumonia, empyema, or hydrochlothorax, but the fact that they clear within 24 to 48 hours indicates that none of these diseases is the cause. It is thought that neonatal opaque right lung results from the transient retention of normal fetal fluid in the right lung
Coors, Sarah M; Cousin, Joshua J; Hagan, Joseph L; Kaiser, Jeffrey R
To test the hypothesis that prophylactic dextrose gel administered to newborn infants at risk for hypoglycemia will increase the initial blood glucose concentration after the first feeding and decrease neonatal intensive care unit (NICU) admissions for treatment of asymptomatic neonatal hypoglycemia compared with feedings alone. This quasi-experimental study allocated asymptomatic at-risk newborn infants (late preterm, birth weight 4000 g, and infants of mothers with diabetes) to receive prophylactic dextrose gel (Insta-Glucose; Valeant Pharmaceuticals North America LLC, Bridgewater, New Jersey); other at-risk infants formed the control group. After the initial feeding, the prophylactic group received dextrose gel (0.5 mL/kg) rubbed into the buccal mucosa. The blood glucose concentration was checked 30 minutes later. Initial glucose concentrations and rate of NICU admissions were compared between the prophylactic group and controls using bivariate analyses. A multivariable linear regression compared first glucose concentrations between groups, adjusting for at-risk categories and age at first glucose concentration. There were 236 subjects (72 prophylactic, 164 controls). The first glucose concentration was not different between the prophylactic and control groups in bivariate analysis (52.1 ± 17.1 vs 50.5 ± 15.3 mg/dL, P = .69) and after adjusting for covariates (P = .18). Rates of NICU admission for treatment of transient neonatal hypoglycemia were 9.7% and 14.6%, respectively (P = .40). Prophylactic dextrose gel did not reduce transient neonatal hypoglycemia or NICU admissions for hypoglycemia. The carbohydrate concentration of Insta-Glucose (77%) may have caused a hyperinsulinemic response, or alternatively, exogenous enteral dextrose influences glucose homeostasis minimally during the first few hours when counter-regulatory mechanisms are especially active. ClinicalTrials.gov: NCT02523222. Copyright © 2018 Elsevier Inc. All
BACKGROUND: Routine care for chylothorax in neonate includes either conservative or surgical approaches. Octreotide, a somatostatin analogue, has been used for the management of patients with refractory chylothorax not responding to conservative management. OBJECTIVES: To assess the efficacy and safety of octreotide in the treatment of chylothorax in neonates. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE and EMBASE (to March 7, 2010). We assessed the reference lists of identified trials and abstracts from the annual meetings of the Pediatric Academic Societies published in Pediatric Research (2002 to 2009) without language restrictions. SELECTION CRITERIA: We planned to include randomised or quasi-randomised controlled trials of octreotide in the treatment of congenital or acquired chylothorax in term or preterm neonates, with any dose, duration or route of administration. DATA COLLECTION AND ANALYSIS: Data on primary (amount of fluid drainage, respiratory support, mortality) and secondary outcomes (side effects) were planned to be collected and analysed using mean difference, relative risk and risk difference with 95% confidence intervals. MAIN RESULTS: No randomised controlled trials were identified. Nineteen case reports of 20 neonates with chylothorax in whom octreotide was used either subcutaneously or intravenously were identified. Fourteen case reports described successful use (resolution of chylothorax), four reported failure (no resolution) and one reported equivocal results following use of octreotide. The timing of initiation, dose, duration and frequency of doses varied markedly. Gastrointestinal intolerance and clinical presentations suggestive of necrotizing enterocolitis and transient hypothyroidism were reported as side effects. AUTHORS\\' CONCLUSIONS: No practice recommendation can be made based on the evidence identified in this review. A prospective registry of
Angelis, Dimitrios; Kubicky, Rita Ann; Zubrow, Alan B.
Maternal Graves’ disease is relatively uncommon with an estimated incidence of 0.4%–1% of all pregnancies, but only 1–5% of newborns delivered to mothers with Graves’ disease develop overt clinical signs and symptoms of hyperthyroidism. Here, we describe a case of a 1380-gram female neonate who was born at 30-week gestation to a mother with Graves’ disease. Our patient presented with hyperthyroidism followed by transient hypothyroidism requiring treatment with levothyroxine. While hyperthyroi...
Alchinova, I B; Yakovenko, E N; Sidnev, D V; Dedaev, S Yu; Sanadze, A G; Karganov, M Yu
An aim of the study was to compare informative value of traditional approach (anti-AChR antibody radioimmunoassay) and evaluation of metabolic shifts by laser correlation spectroscopy in myasthenia gravis. The search for the relationship between the disease severity in 77 patients, 12-80 years and the distribution pattern of subfraction serum components revealed three informative zones: 6-15, 27-67, and 127-223 nm. In patients without disturbances of vital functions, the contribution of the first zone particles into light scatter increases and that of the third zone particles decreases. Considerable differences attaining the level of statistical significance in zones 6 and 20 nm were revealed in the spectra of serum from patients with myasthenia gravis of the same severity with and without thymoma. This opens prospects for dynamic monitoring of the efficiency of therapy.
The acoustic stapedial reflex (ASR) test provides useful information about the function of the auditory system. While it is frequently used with adults and children in a clinical setting, its use with young infants is limited. Presently, there are few data for neonates and inadequate research into the test-retest reliability of the ASR test. This study aimed to establish normative data and evaluate the test-retest reliability of the ASR test in healthy neonates. A cross-sectional experimental design was used to establish ASR normative data and assess the test-retest reliability of ASR thresholds obtained from healthy neonates. Sixty-eight full-term neonates with mean chronological age of 2.5 days (SD = 1.8 day), who passed the automated auditory brainstem response, transient evoked otoacoustic emission, and high frequency (1 kHz) tympanometry (HFT) tests. One randomly selected ear from each neonate was tested using TEOAE (transient evoked otoacoustic emission), HFT, and ASR tests using a 1 kHz probe tone. ASR thresholds were elicited by presenting pure tones of 0.5, 2, and 4 kHz and broadband noise (BBN) separately to the test ear in an ipsilateral stimulation mode. The ASR procedure was repeated to acquire retest data within the same testing session. Descriptive statistics, χ2, and analysis of variance with repeated measures tests were used to analyze ASR data. All neonates exhibited ASR when stimulated by tonal stimuli or BBN. The mean ASRTs (acoustic stapedial reflex thresholds) for the 0.5, 2, and 4 kHz tones were 81.6 ± 7.9, 71.3 ± 7.9, and 65.4 ± 8.7 dB HL, respectively. The mean ASRT for the BBN was estimated to be smaller than 57.2 dB HL, given the limitation of the equipment. The 95th percentiles of the ASRT were 95, 85, 80, and 75 dB HL for the 0.5, 2, and 4 kHz and BBN, respectively. The test-retest reliability of the ASR test for all stimuli was high, with no significant difference in mean ASRTs across the test and retest conditions. Test
Danikowski, K M; Jayaraman, S; Prabhakar, B S
Multiple sclerosis (MS) is a chronic debilitating disease of the central nervous system primarily mediated by T lymphocytes with specificity to neuronal antigens in genetically susceptible individuals. On the other hand, myasthenia gravis (MG) primarily involves destruction of the neuromuscular junction by antibodies specific to the acetylcholine receptor. Both autoimmune diseases are thought to result from loss of self-tolerance, which allows for the development and function of autoreactive lymphocytes. Although the mechanisms underlying compromised self-tolerance in these and other autoimmune diseases have not been fully elucidated, one possibility is numerical, functional, and/or migratory deficits in T regulatory cells (Tregs). Tregs are thought to play a critical role in the maintenance of peripheral immune tolerance. It is believed that Tregs function by suppressing the effector CD4+ T cell subsets that mediate autoimmune responses. Dysregulation of suppressive and migratory markers on Tregs have been linked to the pathogenesis of both MS and MG. For example, genetic abnormalities have been found in Treg suppressive markers CTLA-4 and CD25, while others have shown a decreased expression of FoxP3 and IL-10. Furthermore, elevated levels of pro-inflammatory cytokines such as IL-6, IL-17, and IFN-γ secreted by T effectors have been noted in MS and MG patients. This review provides several strategies of treatment which have been shown to be effective or are proposed as potential therapies to restore the function of various Treg subsets including Tr1, iTr35, nTregs, and iTregs. Strategies focusing on enhancing the Treg function find importance in cytokines TGF-β, IDO, interleukins 10, 27, and 35, and ligands Jagged-1 and OX40L. Likewise, strategies which affect Treg migration involve chemokines CCL17 and CXCL11. In pre-clinical animal models of experimental autoimmune encephalomyelitis (EAE) and experimental autoimmune myasthenia gravis (EAMG), several strategies
Newsom-Davis, J.; Willcox, N.; Calder, L.
We investigated the role of the thymus in 16 patients with myasthenia gravis without thymoma by studying the production of anti-acetylcholine-receptor antibody by thymic and blood lymphocytes cultured alone or together. In 10 responders (with the highest receptor-antibody titers in their plasma), cultured thymic cells spontaneously produced measurable receptor antibody. Receptor-antibody production by autologous blood lymphocytes was enhanced by the addition of responder's thymic cells, irradiated to abrogate antibody production and suppression (P<0.01). This enhancement was greater and more consistent than that by pokeweed mitogen; it depended on viable thymic cells, appeared to be selective for receptor antibody, and correlated with the ratio of thymic helper (OKT4-positive or OKT4+) to suppressor (OKT8+) T cells (P<0.01). These results suggest that myasthenic thymus contains cell-bound acetylcholine-receptor-like material or specific T cells (or both) that can aid receptor-antibody production. This may be relevant to the benefits of thymectomy in myasthenia and to the breakdown in self-tolerance in this and other autoimmune diseases
Newsom-Davis, J.; Willcox, N.; Calder, L.
We investigated the role of the thymus in 16 patients with myasthenia gravis without thymoma by studying the production of anti-acetylcholine-receptor antibody by thymic and blood lymphocytes cultured alone or together. In 10 responders (with the highest receptor-antibody titers in their plasma), cultured thymic cells spontaneously produced measurable receptor antibody. Receptor-antibody production by autologous blood lymphocytes was enhanced by the addition of responder's thymic cells, irradiated to abrogate antibody production and suppression (P<0.01). This enhancement was greater and more consistent than that by pokeweed mitogen; it depended on viable thymic cells, appeared to be selective for receptor antibody, and correlated with the ratio of thymic helper (OKT4-positive or OKT4+) to suppressor (OKT8+) T cells (P<0.01). These results suggest that myasthenic thymus contains cell-bound acetylcholine-receptor-like material or specific T cells (or both) that can aid receptor-antibody production. This may be relevant to the benefits of thymectomy in myasthenia and to the breakdown in self-tolerance in this and other autoimmune diseases.
Heckmann, J M; Uwimpuhwe, H; Ballo, R; Kaur, M; Bajic, Vladimir B.; Prince, S
Complement activation in myasthenia gravis (MG) may damage muscle endplate and complement regulatory proteins such as decay-accelerating factor (DAF) or CD55 may be protective. We hypothesize that the increased prevalence of severe extraocular
Manfredi, Alessandra Kerli da Silva; Zuanetti, Patrícia Aparecida; Mishima, Fabíola; Granzotti, Raphaela Barroso Guedes
OBJETIVO: Analisar as emissões otoacústicas de crianças nascidas de mães soropositivas para o HIV na triagem auditiva neonatal. MÉTODOS: Realizou-se a pesquisa das Emissões Otoacústicas Evocadas por Transiente (EOAT) e do reflexo cócleo-palpebral (RCP) em 247 neonatos, todos nascidos a termo e sem fatores de risco para a audição. O Grupo Controle (GC) foi composto por 167 neonatos e o Grupo Pesquisa (GP) por 80 neonatos expostos ao HIV durante a gestação. Considerou-se "falha" quando o neonat...
Park, Mi-Jeong; Kim, Yun-A; Lee, Shin-Seok; Kim, Byeong-Chae; Kim, Myeong-Kyu; Cho, Ki-Hyun
We report two cases of systemic lupus erythematosus (SLE) in myasthenia gravis (MG) patients who had undergone thymectomy. SLE developed in the patients 3 months or 13 yr after thymectomy, and polyarthritis was the main clinical manifestation of SLE. Both patients fulfilled at least four of the revised criteria for the classification of SLE. In this report, we describe two postthymectomy lupus patients and perform a comparative review of previous cases.
Yang, Dehao; Su, Zhongqian; Wu, Shengjie; Bi, Yong; Li, Xiang; Li, Jia; Lou, Kangliang; Zhang, Hongyu; Zhang, Xu
Oxidative stress and low antioxidant status play a major role in the pathogenesis of inflammatory and autoimmune diseases. Myasthenia gravis (MG) is an autoimmune condition targeting the neuromuscular junction, and its antioxidant status is still controversial. Our study aimed to investigate the correlation between the clinical characteristics of MG and the serum antioxidant status of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine. We measured serum antioxidant molecule levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine in 380 individuals, including 166 MG and 214 healthy controls. We found that MG patients had significantly lower serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine than healthy controls, whether male or female. Moreover, it was also shown in our study that uric acid, albumin and creatinine levels in patients with MG were correlated with disease activity and classifications performed by the Myasthenia Gravis Foundation of America. Our findings demonstrated that serum levels of bilirubin (Tbil, Dbil and Ibil), uric acid, albumin and creatinine were reduced in patients with MG. This suggested an active oxidative process in MG patients who had low antioxidant status.
Sekine, Yasuo; Kawaguchi, Naoki; Hamada, Chikuma; Sekiguchi, Hiromi; Yasufuku, Kazuhiro; Iyoda, Akira; Shibuya, Kiyoshi; Fujisawa, Takehiko
The purpose of this study was to clarify the clinical benefits of perioperative administration of high-dose prednisolone (PSL) combined with extended thymectomy on the long-term outcomes of 116 consecutive patients with generalized myasthenia gravis (MG). A retrospective review was conducted on 116 patients diagnosed with generalized MG who received alternate-day oral administration of high-dose PSL (100 mg/alternate days) and had undergone transsternal extended thymectomy. Incidences of postoperative myasthenic crisis, adverse effects of steroid, long-term outcomes, such as complete stable remission (CSR), pharmacologic remission (PR) or improvement (Imp), and disease recurrence after CSR were evaluated. Six patients (5.2%) experienced post-thymectomy myasthenic crisis. Crude cumulative CSR and PR + CSR rates were 44.8 and 62.7%, respectively. Life table analysis showed that 41.8, 52.8 and 63.4% of the patients were in CSR at 3, 5 and 10 years, respectively. Multivariate analysis revealed that age and pretreatment classification according to the Myasthenia Gravis Foundation of America (MGFA) criteria tended to be independent predictors of CSR. There were 6.9% with compressive vertebral fracture, 13.8% with cataract, and 5.2% with steroid-induced diabetes. Life table analysis revealed that recurrence rates after CSR were 36.8 and 46.0% at 3 and 5 years, respectively. Patients with thymoma had a significantly higher rate of recurrence than those without thymoma (p = 0.001). Alternate-day administration of high-dose prednisolone reduced the risk of post-thymectomy myasthenic crisis. Presence of thymoma was a risk factor for MG recurrence after CSR.
Weinberg, Lori E; Dinsmoor, Mara J; Silver, Richard K
Diabetes insipidus is rare in pregnancy. It is characterized by hypoosmolar polyuria and may be central, nephrogenic, or transient in etiology; the latter is presumably related to excess placental vasopresinase production. In theory, fetal effects of this endocrine condition may include hydramnios secondary to fetal polyuria. A pregnant patient developed rapid-onset second-trimester hydramnios that prompted a thorough fetal and maternal evaluation. She ultimately was diagnosed with transient diabetes insipidus of pregnancy because of an abrupt change in her voiding pattern at 20 weeks of gestation, significant polydipsia, and laboratory studies that revealed a hypoosmolar polyuria with normal serum and urine electrolytes. Transient neonatal polyuria also was confirmed in association with this unique maternal endocrine syndrome. The most likely cause of hydramnios in this case is transient maternal diabetes insipidus of pregnancy from excessive secretion of placental vasopressinase resulting in fetal polyuria. In cases of hydramnios of unknown etiology, if a history of maternal polyuria is elicited and confirmed, diabetes insipidus of pregnancy may play a role in some cases.
Raaijmakers, Anke; Zhang, Zhen-Yu; Levtchenko, Elena; Simons, Sinno Hp; Cauwenberghs, Nicholas; Heuvel, Lambertus P van den; Jacobs, Lotte; Staessen, Jan A; Allegaert, Karel
Ibuprofen exposure results in acute transient renal dysfunction in preterm neonates, but we are unaware of data on long-term renal safety. In a previously studied cohort of extreme low birth weight (ELBW, ibuprofen. In this post hoc analysis, we linked markers of renal function in young adolescence in ELBW cases with their perinatal (prenatal maternal, setting at birth, treatment modalities including drug prescription during neonatal stay, neonatal creatinine values, postdischarge growth) characteristics, including but not limited to ibuprofen exposure during neonatal stay. Ibuprofen exposure was not associated with significant differences in renal length or eGFR cysC . Moreover, we were unable to identify any other risk factor (perinatal characteristics, postnatal creatinine trends, postdischarge growth) on renal outcome in this cohort. Neonatal exposure to ibuprofen did not affect renal function. Larger studies are needed to explore the confounders of variability in renal function in former ELBW cases. This matters since ELBW relates to risk for hypertension, cardiovascular events and renal disease in later life and identification of risk factors holds the promise of secondary prevention. NCT02147457. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
Smit, L. M.; Jennekens, F. G.; Veldman, H.; Barth, P. G.
A new form of congenital myasthenia is described. An infant whose foetal movements during pregnancy had been weak presented at birth with muscle weakness and multiple contractures of the lower limbs. The clinical course was characterised by myasthenic crises during febrile illnesses.
Full Text Available Background: Congenital hypothyroidism (CH is the most common endocrine diseases and one of the major causes of preventable mental retardation. This study was conducted to investigate the prevalence of transient and permanent congenital hypothyroidism in Kurdistan province, Iran.Materials and Methods: In this cross-sectional study, all registered congenital hypothyroidism neonate of health centers of cities covered by Kurdistan University of Medical Sciences during 2006 to 2014 entered to study. Demographic and laboratory information of CH neonates was collected and entered into the Stata-12 and was analyzed using student t-test and Chi-square statistic and P- value less than 0.05 was considered.Results: Overall incidence rate during 2006 to 2014 for province was 1.8, 2.3, 3.2, 4.3, 3.3, 4.0, 3.6, 4.6 and 2.7, respectively per 1000 neonates in this period. The number of diagnosed patients was 855 cases including 519 (60.7% boys and 336 (39.3% girls who 516 (60.4% cases were from urban areas. Of the total patients, 202 (22.6% were permanent. There was no significant difference between gender, location, type of childbirth, and season of birth with transient and permanent types of disease (P˃0.05; while, there was a significant statistical relationship between consanguineous marriages and congenital hypothyroidism (P
Nakasone, Etsuko; Nakayama, Masayuki; Bando, Masashi; Endo, Shunsuke; Hironaka, Mitsugu; Sugiyama, Yukihiko
A 62-year-old man was admitted to our hospital with a 2-month history of progressive cough and dyspnea. He had undergone thymectomy for thymoma with myasthenia gravis. Adjuvant radiation of 50 Gy had been performed until 6 months before the symptoms developed. Chest computed tomography showed infiltrative findings even outside the irradiated area. We diagnosed radiation-related pneumonia, and 30 mg per day prednisolone was initiated. On the final day, he developed bilateral tension pneumothorax. After chest tube drainage, the right S 5 bulla was resected with video-assisted thoracoscopic surgery (VATS). The right pneumothorax caused the bilateral tension pneumothorax, because the right and left thoracic cavity communicated in the anterior mediastinum after thymectomy. We should be aware of the risk of bilateral tension pneumothorax following radiation-related pneumonia after extended thymectomy and adjuvant radiation in patients with myasthenia gravis. (author)
Full Text Available Maternal Graves’ disease is relatively uncommon with an estimated incidence of 0.4%–1% of all pregnancies, but only 1–5% of newborns delivered to mothers with Graves’ disease develop overt clinical signs and symptoms of hyperthyroidism. Here, we describe a case of a 1380-gram female neonate who was born at 30-week gestation to a mother with Graves’ disease. Our patient presented with hyperthyroidism followed by transient hypothyroidism requiring treatment with levothyroxine. While hyperthyroid, she was treated with methimazole, iodine, and a beta-blocker. 20 days after the initiation of methimazole, she developed neutropenia. The neutrophil counts started to improve immediately after the initiation of the weaning of methimazole. To the best of our knowledge, this is the first case reported in the literature of methimazole induced neutropenia in a preterm infant being treated for neonatal Graves’ disease.
Adam J. Lake
Full Text Available Myasthenia gravis (MG is a rare autoimmune disease that leads to progressive muscle weakness and is common during female reproductive years. The myasthenic mother and her newborn must be observed carefully, as complications during all stages of pregnancy and the puerperium may arise suddenly. Preeclampsia is a common obstetrical condition for which magnesium sulfate is used for seizure prophylaxis. However, magnesium sulfate is strongly contraindicated in MG as it impairs already slowed nerve-muscle connections. Similarly, many first-line antihypertensive medications, including calcium channels blockers and β-blockers, may lead to MG exacerbation. This case describes the effective obstetrical management of a patient with MG who developed severe preeclampsia. The effective use of levetiracetam and various antihypertensive medications including intravenous labetalol is described. A review of the ten reported cases of MG complicated by preeclampsia is examined to aggregate observations of clinical care, with focus on delivery methods, anticonvulsants, and antihypertensive medications.
Full Text Available Myasthenia gravis (MG is caused by antibodies that react mainly with the acetylcholine receptor on the postsynaptic site of the neuromuscular junction. A wide range of clinical presentations and associated features allow MG to be classified into subtypes based on autoantibody status. Striational antibodies, which react with epitopes on the muscle proteins titin, ryanodine receptor (RyR, and Kv1.4, are frequently found in MG patients with late-onset and thymoma. Antititin and anti-RyR antibodies are determined by enzyme-linked immunosorbent assay or immunoblot. More recently, a method for the detection of anti-Kv1.4 autoantibodies has become available, involving 12–15% of all MG patients. The presence of striational antibodies is associated with more severe disease in all MG subgroups. Anti-Kv1.4 antibody is a useful marker for the potential development of lethal autoimmune myocarditis and response to calcineurin inhibitors. Detection of striational antibodies provides more specific and useful clinical information in MG patients.
Mantegazza, Renato; Cordiglieri, Chiara; Consonni, Alessandra; Baggi, Fulvio
Myasthenia gravis (MG) is a chronic autoimmune disease caused by the immune attack of the neuromuscular junction. Antibodies directed against the acetylcholine receptor (AChR) induce receptor degradation, complement cascade activation, and postsynaptic membrane destruction, resulting in functional reduction in AChR availability. Besides anti-AChR antibodies, other autoantibodies are known to play pathogenic roles in MG. The experimental autoimmune MG (EAMG) models have been of great help over the years in understanding the pathophysiological role of specific autoantibodies and T helper lymphocytes and in suggesting new therapies for prevention and modulation of the ongoing disease. EAMG can be induced in mice and rats of susceptible strains that show clinical symptoms mimicking the human disease. EAMG models are helpful for studying both the muscle and the immune compartments to evaluate new treatment perspectives. In this review, we concentrate on recent findings on EAMG models, focusing on their utility and limitations. PMID:27019601
Radetti, G; Zavallone, A; Gentili, L; Beck-Peccoz, P; Bona, G
Thyroid hormones have been shown to be absolutely necessary for early brain development. During pregnancy, both maternal and foetal thyroid hormones contribute to foetal brain development and maternal supply explains why most of the athyreotic newborns usually do not show any signs of hypothyroidism at birth. Foetal and/or neonatal hypothyroidism is a rare disorder. Its incidence, as indicated by neonatal screening, is about 1:4000. Abnormal thyroid development (i.e. agenesia, ectopic gland, hypoplasia) or inborn errors in thyroid hormone biosynthesis are the most common causes of permanent congenital hypothyroidism. Recent studies reported that mutations involving Thyroid Transcriptor Factors (TTF) such as TTF-1, TTF-2, PAX-8 play an important role in altered foetal thyroid development. Deficiency of transcriptor factor (Pit-1, Prop-1, LHX-3) both in mother and in the foetus represents another rare cause of foetal hypothyroidism. At birth clinical picture may be not always so obvious and typical signs appear only after several weeks but a delayed diagnosis could have severe consequences consisting of delayed physical and mental development. Even if substitutive therapy is promptly started some learning difficulties might still arise suggesting that intrauterine adequate levels of thyroid hormones are absolutely necessary for a normal neurological development. Placental transfer of maternal antithyroid antibodies inhibiting fetal thyroid function can cause transient hypothyroidism at birth. If the mother with thyroid autoimmune disease is also hypothyroid during pregnancy and she doesn't receive substitutive therapy, a worse neurological outcome may be expected for her foetus. Foetal and/or neonatal hyperthyroidism is a rare condition and its incidence has been estimated around 1:4000-40000, according to various authors. The most common causes are maternal thyroid autoimmune disorders, such as Graves' disease and Hashimoto's thyroiditis. Rarer non autoimmune causes
Algert Charles S
Full Text Available Abstract Background Despite widespread use of neonatal hospital discharge data, there are few published reports on the accuracy of population health data with neonatal diagnostic or procedure codes. The aim of this study was to assess the accuracy of using routinely collected hospital discharge data in identifying neonatal morbidity during the birth admission compared with data from a statewide audit of selected neonatal intensive care (NICU admissions. Methods Validation study of population-based linked hospital discharge/birth data against neonatal intensive care audit data from New South Wales, Australia for 2,432 babies admitted to NICUs, 1994–1996. Sensitivity, specificity and positive predictive values (PPV with exact binomial confidence intervals were calculated for 12 diagnoses and 6 procedures. Results Sensitivities ranged from 37.0% for drainage of an air leak to 97.7% for very low birthweight, specificities all exceeded 85% and PPVs ranged from 70.9% to 100%. In-hospital mortality, low birthweight (≤1500 g, retinopathy of prematurity, respiratory distress syndrome, meconium aspiration, pneumonia, pulmonary hypertension, selected major anomalies, any mechanical ventilation (including CPAP, major surgery and surgery for patent ductus arteriosus or necrotizing enterocolitis were accurately identified with PPVs over 92%. Transient tachypnea of the newborn and drainage of an air leak had the lowest PPVs, 70.9% and 83.6% respectively. Conclusion Although under-ascertained, routinely collected hospital discharge data had high PPVs for most validated items and would be suitable for risk factor analyses of neonatal morbidity. Procedures tended to be more accurately recorded than diagnoses.
Ford, Jane B; Roberts, Christine L; Algert, Charles S; Bowen, Jennifer R; Bajuk, Barbara; Henderson-Smart, David J
Background Despite widespread use of neonatal hospital discharge data, there are few published reports on the accuracy of population health data with neonatal diagnostic or procedure codes. The aim of this study was to assess the accuracy of using routinely collected hospital discharge data in identifying neonatal morbidity during the birth admission compared with data from a statewide audit of selected neonatal intensive care (NICU) admissions. Methods Validation study of population-based linked hospital discharge/birth data against neonatal intensive care audit data from New South Wales, Australia for 2,432 babies admitted to NICUs, 1994–1996. Sensitivity, specificity and positive predictive values (PPV) with exact binomial confidence intervals were calculated for 12 diagnoses and 6 procedures. Results Sensitivities ranged from 37.0% for drainage of an air leak to 97.7% for very low birthweight, specificities all exceeded 85% and PPVs ranged from 70.9% to 100%. In-hospital mortality, low birthweight (≤1500 g), retinopathy of prematurity, respiratory distress syndrome, meconium aspiration, pneumonia, pulmonary hypertension, selected major anomalies, any mechanical ventilation (including CPAP), major surgery and surgery for patent ductus arteriosus or necrotizing enterocolitis were accurately identified with PPVs over 92%. Transient tachypnea of the newborn and drainage of an air leak had the lowest PPVs, 70.9% and 83.6% respectively. Conclusion Although under-ascertained, routinely collected hospital discharge data had high PPVs for most validated items and would be suitable for risk factor analyses of neonatal morbidity. Procedures tended to be more accurately recorded than diagnoses. PMID:18021458
Pavolucci, Lucia; Giannini, Giulia; Giannoccaro, Maria Pia; Foschini, Maria Pia; Lang, Bethan; Avoni, Patrizia; Tinuper, Paolo; Vincent, Angela; Liguori, Rocco
Merkel cell carcinoma is a rare cutaneous, aggressive tumor. Although it shares many neuroendocrine features with small cell lung carcinoma, it has only occasionally been reported with paraneoplastic neurological syndromes. A healthy 67-year-old man developed acute ataxia, vertigo, and nausea. Subsequently he also developed dysarthria, diplopia, xerostomia, fatigability and progressive anorexia. He underwent a full diagnostic workup and was found to have a high titer of voltage-gated calcium channel antibodies in serum and cerebrospinal fluid, neurophysiological findings compatible with Lambert-Eaton myasthenia and neurological signs compatible with cerebellar degeneration. A positron emission tomography study revealed a hypermetabolic lesion in the axilla, subsequently biopsied and consistent with Merkel cell carcinoma. In most previous reports, neurological symptoms preceded the Merkel cell carcinoma diagnosis, and the primary localization was in lymph nodes. This tumor should be considered in patients with paraneoplastic syndrome, and particularly Lambert-Eaton myasthenia after exclusion of small cell lung carcinoma. Muscle Nerve 56: 998-1000, 2017. © 2016 Wiley Periodicals, Inc.
Full Text Available In 1970s, presence of thymic tissue in anterior mediastinal adipose tissue around the thymus was found. Here we report a case of ectopic thymic tissue in the mediastinum and the possible relevance of this distribution of thymic tissue outside thymus to the therapeutic yield of thymectomies in myasthenia gravis. A 30-year lady with myasthenia gravis (nonthymomatous presented with difficulty in swallowing and breathing for the last 1 years. She was under medical treatment but with little improvement. She underwent extended thymectomy, after which an en bloc resection of the anterior mediastinal fat tissues from pericardium and pleura, including the thymus, was performed. Grossly the soft tissue specimen taken from near left lateral area of heart was fibrofatty tissue. Microscopically isolated thymic tissues were seen interspersed among the fatty tissues composed of mature lymphocytes, epithelial cells and few Hassall's corpuscles were observed. Thymus specimen was within normal histological limits. To ensure complete removal, the adipose tissue at the anterior mediastinum as well as the gross thymus should be removed. Thymic tissue incidence in individual locations was as follows: Retrothyroid, 3(6%; peritracheal, 5 (10%; retrotracheal, 1 (2%; right phrenic nerve, 2 (4%; left phrenic nerve, 14 (28%; right recurrent laryngeal nerve, 2 (4%; left recurrent laryngeal nerve, 2 (4% and periaortic, 0. Trans-sternal thymectomy was found to be beneficial to all patients of mild-to-moderate myasthenia gravis with 70.2% patients showing improvement postoperatively.
de Vries, Aleida G. M.; Bakker-van Waarde, Willie M.; Dassel, Anne C. M.; Losekoot, Monique; Duiker, Evelien W.; Gouw, Annette S. H.; Bodewes, Frank A. J. A.
We report a novel phenotype of a hepatocyte nuclear factor homeobox A (HNF1A) mutation (heterozygote c.130dup, p.Leu44fs) presenting with transient neonatal cholestasis, subsequently followed by persistent elevation of transaminases, maturity-onset diabetes of the young (MODY) type 3 and
The clinical examination of the CNS in the neonate is often difficult in cases of complex pathology. Diagnostic imaging of the neonatal brain has become extremely useful and in the last decade has developed in two main directions: CT and US. MR imaging has been used recently with varying success in the diagnosis of pathology in the neonatal brain. Despite technical difficulties, this imaging method is likely to become increasingly important in the neonate. The paper examines the normal neonatal brain anatomy as seen with the different modalities, followed by pathologic conditions. Attention is directed to the common pathology, in asphyxiated newborns, the patholphysiology of intraventicular hemorrhage and periventricular leukomalacia in the preterm neonate, and hypoxic-ischemic brain injury in the term neonate. Pitfalls, artifacts, and problems in image interpretation are illustrated. Finally, the subsequent appearance of neonatal pathology later in infancy and childhood is discussed
Sharma, Deepak; Farahbakhsh, Nazanin; Shastri, Sweta; Sharma, Pradeep
Neonatal hypertension (HT) is a frequently under reported condition and is seen uncommonly in the intensive care unit. Neonatal HT has defined arbitrarily as blood pressure more than 2 standard deviations above the base as per the age or defined as systolic BP more than 95% for infants of similar size, gestational age and postnatal age. It has been diagnosed long back but still is the least studied field in neonatology. There is still lack of universally accepted normotensive data for neonates as per gestational age, weight and post-natal age. Neonatal HT is an important morbidity that needs timely detection and appropriate management, as it can lead to devastating short-term effect on various organs and also poor long-term adverse outcomes. There is no consensus yet about the treatment guidelines and majority of treatment protocols are based on the expert opinion. Neonate with HT should be evaluated in detail starting from antenatal, perinatal, post-natal history, and drug intake by neonate and mother. This review article covers multiple aspects of neonatal hypertension like definition, normotensive data, various etiologies and methods of BP measurement, clinical features, diagnosis and management.
Reginatto, Flávia Pereira; DeVilla, Damie; Muller, Fernanda M; Peruzzo, Juliano; Peres, Letícia P; Steglich, Raquel B; Cestari, Tania F
To determine the prevalence of neonatal dermatological findings and analyze whether there is an association between these findings and neonatal and pregnancy characteristics and seasonality. Newborns from three maternity hospitals in a Brazilian capital city were randomly selected to undergo dermatological assessment by dermatologists. 2938 neonates aged up to three days of life were randomly selected, of whom 309 were excluded due to Intensive Care Unit admission. Of the 2530 assessed neonates, 49.6% were Caucasians, 50.5% were males, 57.6% were born by vaginal delivery, and 92.5% of the mothers received prenatal care. Some dermatological finding was observed in 95.8% of neonates; of these, 88.6% had transient neonatal skin conditions, 42.6% had congenital birthmarks, 26.8% had some benign neonatal pustulosis, 2% had lesions secondary to trauma (including scratches), 0.5% had skin malformations, and 0.1% had an infectious disease. The most prevalent dermatological findings were: lanugo, which was observed in 38.9% of the newborns, sebaceous hyperplasia (35%), dermal melanocytosis (24.61%), skin desquamation (23.3%), erythema toxicum neonatorum (23%), salmon patch (20.4%), skin erythema (19%), genital hyperpigmentation (18.4%), eyelid edema (17.4%), milia (17.3%), genital hypertrophy (12%), and skin xerosis (10.9%). Dermatological findings are frequent during the first days of life and some of them characterize the newborn's skin. Mixed-race newborns and those whose mothers had some gestational risk factor had more dermatological findings. The gestational age, newborn's ethnicity, gender, Apgar at the first and fifth minutes of life, type of delivery, and seasonality influenced the presence of specific neonatal dermatological findings. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.
FRANCISCO MARCOS B. CUNHA
Full Text Available Foram pesquisados aspectos históricos da miastenia grave desde as primeiras descrições da doença em 1672, pelo clínico inglês Thomas Willis. São descritas as dificuldades encontradas no manuseio dos primeiros pacientes diagnosticados. Pesquisaram-se fatos históricos ligados à investigação da doença, o tratamento, bem como curiosidades pouco citadas na literatura.We studied historical aspects of myasthenia gravis starting from its first description by the English physician, Sir Thomas Willis, in 1672. We also describe the difficulties in managing triating the first diagnosed patient. Historical facts related to the investigation and the initial treatment of this disorder as well as curiosities seldom mentioned in the literature are part of this paper.
Raggi, Alberto; Leonardi, Matilde; Ayadi, Roberta; Antozzi, Carlo; Maggi, Lorenzo; Baggi, Fulvio; Mantegazza, Renato
In this study we assess the Italian version of the 15-item Myasthenia Gravis Quality-of-Life questionnaire (MG-QOL15). The validation protocol included the MG-QOL15, the 36-item Short Form (SF-36), the Besta Neurological Institute Rating Scale for Myasthenia Gravis, and the MG-Composite. We used the Cronbach α to test reliability, the Spearman correlation to test short-term test-retest, the Kruskal-Wallis test to assess differences in MG-QOL15 between patients with different disease severity, and the Wilcoxon signed-rank test to assess sensitivity to change. Seventy-two patients were enrolled in the study. The mean MG-QOL15 score was 15.2 ± 12.2, with α = 0.93 and test-retest correlation = 0.93. Compared with the SF-36, the MG-QOL15 was superior in differentiating patients with different MG types (P = 0.041) and severity (P = 0.004), showed higher sensitivity to change (P = 0.003 for improved and P = 0.024 for worsened patients), and had higher correlations with the MG-Composite (rho = 0.367 vs. -0.213 and -0.154). The Italian version of the MG-QOL15 is valid, reliable, stable, and sensitive to changes. Muscle Nerve 56: 716-720, 2017. © 2016 Wiley Periodicals, Inc.
Mohammad Kazem Sabzehei
Full Text Available Background: Jaundice is a common condition among neonates. Prolonged unconjugated hyperbilirubinemia occurs when jaundice persists beyond two weeks in term neonates and three weeks in preterm neonates. This study aimed to determine the etiologies of prolonged unconjugated hyperbilirubinemia in infants admitted to the neonatal ward of Besat Hospital in Hamadan, Iran. Methods: This study was conducted on all infants diagnosed with prolonged unconjugated hyperbilirubinemia during 2007-2012 in the neonatal ward of Besat Hospital in Hamadan, Iran. Demographic characteristics of infants, physical examination and laboratory findings were collected and analyzed to determine the etiologies of neonatal hyperbilirubinemia. Results: In total, 100 infants diagnosed with neonatal hyperbilirubinemia were enrolled in this study, including 49 male and 51 female neonates with mean age of 20±1 days and mean bilirubin level of 17.5±4.0 mg/dL. Main causes of hyperbilirubinemia were urinary tract infection, ABO incompatibility, hypothyroidism and glucose-6-phosphate dehydrogenase deficiency in 14%, 5%, 6% and 5% of neonates, respectively. Moreover, unknown etiologies, such as breastfeeding, were detected in 70% of the studied infants. Conclusion: According to the results of this study, determining the main causes of prolonged unconjugated hyperbilirubinemia in neonates is of paramount importance. In the majority of cases, neonatal hyperbilirubinemia is associated with physiological factors, such as breastfeeding.
Sizakele L.T. Khoza
Full Text Available Background: Neonatal pain management has received increasing attention over the past four decades. Research into the effects of neonatal pain emphasises the professional, ethical and moral obligations of staff to manage pain for positive patient outcomes. However, evaluation studies continuously report evidence of inadequate neonate pain management and a gap between theory and practice. Objective: This study reviewed current practice in neonatal pain management to describe the knowledge, attitudes and practices of nurses and doctors regarding pain management for neonates in two academic hospitals. Method: A non-experimental, prospective quantitative survey, the modified Infant Pain Questionnaire, was used to collect data from 150 nurses and doctors working in the neonatal wards of two academic hospitals in central Gauteng. Results: The response rate was 35.33% (n = 53, most respondents being professional nurses (88.68%; n = 47 working in neonatal intensive care units (80.77%; n = 42; 24 (45.28% had less than 5 years’ and 29 respondents 6 or more years’ working experience in neonatal care. A review of pain management in the study setting indicated a preference for pharmacological interventions to relieve moderate to severe pain. An association (p < 0.05 was found between pain ratings on 5 procedures and frequency of administration of pharmacological pain management. Two-thirds of respondents (64% reported that there were no pain management guidelines in the neonatal wards in which they worked. Conclusion: The interventions to manage moderate neonatal pain are in line with international guidelines. However, neonatal pain management may not occur systematically based on prior assessment of neonatal pain, choice of most appropriate intervention and evaluation. This study recommends implementation of a guideline to standardise practice and ensure consistent and adequate pain management in neonates.
Tero T Kivelä
Full Text Available From 7% to 10% of all retinoblastomas and from 44% to 71% of familial retinoblastomas in developed countries are diagnosed in the neonatal period, usually through pre- or post-natal screening prompted by a positive family history and sometimes serendipitously during screening for retinopathy of prematurity or other reasons. In developing countries, neonatal diagnosis of retinoblastoma has been less common. Neonatal retinoblastoma generally develops from a germline mutation of RB1, the retinoblastoma gene, even when the family history is negative and is thus usually hereditary. At least one-half of infants with neonatal retinoblastoma have unilateral tumors when the diagnosis is made, typically the International Intraocular Retinoblastoma Classification (Murphree Group B or higher, but most germline mutation carriers will progress to bilateral involvement, typically Group A in the fellow eye. Neonatal leukokoria usually leads to the diagnosis in children without a family history of retinoblastoma, and a Group C tumor or higher is typical in the more advanced involved eye. Almost all infants with neonatal retinoblastoma have at least one eye with a tumor in proximity to the foveola, but the macula of the fellow eye is frequently spared. Consequently, loss of reading vision from both eyes is exceptional. A primary ectopic intracranial neuroblastic tumor known as trilateral retinoblastoma is no more common after neonatal than other retinoblastoma. For many reasons, neonatal retinoblastoma may be a challenge to eradicate, and the early age at diagnosis and relatively small tumors do not guarantee the preservation of both eyes of every involved child. Oncology nurses can be instrumental in contributing to better outcomes by ensuring that hereditary retinoblastoma survivors receive genetic counseling, by referring families of survivors to early screening programs when they are planning for a baby, and by providing psychological and practical support
Szyfter, Witold; Wróbel, Maciej; Radziszewska-Konopka, Marzanna; Szyfter-Harris, Joanna; Karlik, Michał
The aim of this paper is to share our experience and observations in running the Universal Neonatal Hearing Screening Program on a national level, present results and indicate some problems that have arisen during these 4 years. Polish Universal Neonatal Hearing Screening Program started back in 2002 in all neonatal units in Poland. Implemented testing methods consisted of test of transient evoked otoacoustic emission (TEOAE) performed in all new born children in their first 2-3 days of life and auditory brainstem response testing (ABR) conducted on children, who did not meet the TEOAE pass criteria. Additional questionnaire registered information on ototoxic drugs and family history of hearing impairment in every newborn. Diagnosed children were further referred for treatment and rehabilitation. After 4 years of running the program (between 2003 and 2006) a total number of 1,392,427 children were screened for hearing impairment, what stands for 96.3% of all delivered babies, registered in Poland. The screening program enabled to identify and refer for further treatment 2485 children with various types of hearing loss, 312 with profound (0.02% of population) and 145 with severe sensorineural hearing loss (0.11% of population). Our results indicate the accuracy of newborn hearing screening which remain an issue. Although improvement is needed in both intervention systems and diagnostic follow-up of hospitals, the Polish Universal Neonatal Hearing Program fully has achieved the main goal, the identification and treatment of hearing impaired children.
Rodolico, Carmelo; Parisi, Daniela; Portaro, Simona; Biasini, Fiammetta; Sinicropi, Stefano; Ciranni, Annamaria; Toscano, Antonio; Messina, Sonia; Musumeci, Olimpia; Vita, Giuseppe; Girlanda, Paolo
Myasthenia gravis (MG) is an autoimmune disorder presenting with fluctuating, fatigable muscle weakness. Initial symptoms classically involve ocular and proximal limb muscles. Rarely, MG may onset with unusual features, so it can be misdiagnosed with other neuromuscular diseases. To describe unusual and atypical presentations of MG in a large cohort of patients, considering and discussing diagnostic difficulties and pitfalls. We report on 21 out of 508 MG patients, coming to our department in the last 27 years and presenting with atypical or unusual features. The diagnosis was achieved performing a careful clinical examination, a proper neurophysiological assessment, the neostigmine test, the AChR and MuSK antibodies assay and chest CT-scan. Patients with atypical/unusual MG onset were the 4.4% of all MG patients population. We describe seven different clinical categories: asymmetric distal upper limbs weakness, foot drop, isolated triceps brachii weakness and foot drop, post exertional axial weakness with dropped head, acute facial dyplegia, limb-girdle MG and MG with sudden lower limbs weakness and recurrent falls. Atypical and unusual presentations may increase the risk to misdiagnose or delay MG diagnosis. Isolated limb-girdle presentation is the most frequent atypical form in our series.
Tanimura, Shigeo; Banba, Jiro; Masaki, Mikio; Irimoto, Masahiro; Matsushita, Akira
Comparison of radiographical findings of the thymus between pneumomediastinography and computed tomography were studied in 35 patients with myasthenia gravis. The patients consisted of 10 patients with thymoma and 25 without thymoma confirmed at the operations. Pneumomediastinography was very useful to discern whether the thymoma was invasive or noninvasive, but not contributory to know whether the thymus was composed of folicular lymphoid hyperplasia or normal thyimic tissues. Computed tomography was also useful to dertermine the localization and the invasiveness of the thymoma, but not helpful to know whether the thymus was of follicular lymphoid hyperplasia or normal tissues. However, the finding of ''reticular pattern''-many small nodules scattered resicularly in the thymus-in computed tomography could be regarded as a sign suggesting follicular lymphoid hyperplasia of the thymus. Therfore, both pneumomediastinography and computed tomography were very useful in the diagnosis of the localization and the invasiveness of the thymoma but not for the diagnosis of follicular lymphoid hyperplasia of the thymus. Neverethless the finding of ''reticular pattern'' computred tomography was helpful in the diagnosis of follicular lymphoid hyperplasia. (author)
Tanimura, Shigeo; Sakaguchi, Kozo; Tomoyasu, Hiroshi; Banba, Jiro; Masaki, Mikio; Kurosaki, Atsuko; Matsushita, Hisashi [Toranomon Hospital, Tokyo (Japan)
Comparison of preoperative CT diagnosis and histopathological diagnosis for the thymus were studied in 39 patients with myasthenia gravis. The patients consisted of 10 patients with thymoma and 29 without thymoma confirmed at the operation. CT diagnosis was 11 thymomas, 18 thymic hyperplasias and 10 normal thymuses. Eleven thymomas revealed histopathologically 9 thymomas, one follicular lymphoid hyperplasia (FLH) and one involved thymus. Out of 18 thymic hyperplasias 15 cases were FLH and 3 involved thymus. There were 5 involved thymuses, 4 FLHs and one thymoma in the 10 normal thymuses on CT. The finding of `reticular pattern`, many small nodules scattered reticularly in the thymus, in computed tomography could be regarded as a sign suggesting FLH of the thymus. The accuracy of this finding of CT was 83% for FLH. The finding of thymoma on CT revealed 82% of the accuracy. Therefore, CT was very useful in the diagnosis of the localization of the thymoma but not for the diagnosis of FLH of the thymus. Nevertheless the finding of `reticular pattern` on CT was helpful in the diagnosis of FLH. (author).
Tanimura, Shigeo; Sakaguchi, Kozo; Tomoyasu, Hiroshi; Banba, Jiro; Masaki, Mikio; Kurosaki, Atsuko; Matsushita, Hisashi
Comparison of preoperative CT diagnosis and histopathological diagnosis for the thymus were studied in 39 patients with myasthenia gravis. The patients consisted of 10 patients with thymoma and 29 without thymoma confirmed at the operation. CT diagnosis was 11 thymomas, 18 thymic hyperplasias and 10 normal thymuses. Eleven thymomas revealed histopathologically 9 thymomas, one follicular lymphoid hyperplasia (FLH) and one involved thymus. Out of 18 thymic hyperplasias 15 cases were FLH and 3 involved thymus. There were 5 involved thymuses, 4 FLHs and one thymoma in the 10 normal thymuses on CT. The finding of 'reticular pattern', many small nodules scattered reticularly in the thymus, in computed tomography could be regarded as a sign suggesting FLH of the thymus. The accuracy of this finding of CT was 83% for FLH. The finding of thymoma on CT revealed 82% of the accuracy. Therefore, CT was very useful in the diagnosis of the localization of the thymoma but not for the diagnosis of FLH of the thymus. Nevertheless the finding of 'reticular pattern' on CT was helpful in the diagnosis of FLH. (author)
Ntigurirwa, Placide; Mellor, Kathy; Langer, Daniel; Evans, Mari; Robertson, Emily; Tuyisenge, Lisine; Groves, Alan; Lissauer, Tom
A health partnership to improve hospital based neonatal care in Rwanda to reduce neonatal mortality was requested by the Rwandan Ministry of Health. Although many health system improvements have been made, there is a severe shortage of health professionals with neonatal training. Following a needs assessment, a health partnership grant for 2 years was obtained. A team of volunteer neonatologists and paediatricians, neonatal nurses, lactation consultants and technicians with experience in Rwanda or low-income countries was assembled. A neonatal training program was provided in four hospitals (the 2 University hospitals and 2 district hospitals), which focused on nutrition, provision of basic respiratory support with nasal CPAP (Continuous Positive Airway Pressure), enhanced record keeping, thermoregulation, vital signs monitoring and infection control. To identify if care delivery improved, audits of nutritional support, CPAP use and its complications, and documentation in newly developed neonatal medical records were conducted. Mortality data of neonatal admissions was obtained. Intensive neonatal training was provided on 27 short-term visits by 10 specialist health professionals. In addition, a paediatric doctor spent 3 months and two spent 6 months each providing training. A total of 472 training days was conducted in the neonatal units. For nutritional support, significant improvements were demonstrated in reduction in time to initiation of enteral feeds and to achieve full milk feeds, in reduction in maximum postnatal weight loss, but not in days for regaining birth weight. Respiratory support with bubble CPAP was applied to 365 infants in the first 18 months. There were no significant technical problems, but tissue damage, usually transient, to the nose and face was recorded in 13%. New medical records improved documentation by doctors, but nursing staff were reluctant to use them. Mortality for University teaching hospital admissions was reduced from 23
Full Text Available Myasthenia Gravis (MG is an autoimmune disorder, which may lead to paralysis and even death if not treated on time. One of its primary symptoms is severe muscular weakness, initially arising in the eye muscles. Testing the mobility of the eyeball can help in early detection of MG. In this study, software was designed to analyze the ability of the eye muscles to focus in various directions, thus estimating the MG risk. Progressive weakness in gazing at the directions prompted by the software can reveal abnormal fatigue of the eye muscles, which is an alert sign for MG. To assess the user’s ability to keep gazing at a specified direction, a fuzzy algorithm was applied to images of the user’s eyes to determine the position of the iris in relation to the sclera. The results of the tests performed on 18 healthy volunteers and 18 volunteers in early stages of MG confirmed the validity of the suggested software.
The development of validated assessment tools for evaluating disease status and response to interventions in patients with myasthenia gravis (MG) has been driven by clinical studies of emerging MG therapies. However, only a small proportion of MG-focused neurology practices have adopted these assessment tools for routine clinical use. This article reviews the suitability of 5 assessment instruments for incorporation into clinical practice, which should be driven by their ability to contribute to improved patient outcomes, and to be implemented within practice personnel and resource constraints. It is recommended that assessments based on both physician-evaluated and patient-reported outcomes be selected, to adequately evaluate both point-in-time symptom load and functional impact of MG symptoms over time. Provider resource allocation and reimbursement issues may be the most significant roadblocks to successful ongoing use of these tools; to that end, the addition of regular assessments to MG standards of care is recommended.
Creutzig, U; Ritter, J; Vormoor, J; Eschenbach, C; Dickerhoff, R; Burdach, S; Scheel-Walter, H G; Kühl, J; Schellong, G
Transient neonatal myeloproliferative disorders (TMD's) indistinguishable from acute leukaemia by clinical and morphological criteria have been described in neonates with Down's syndrome. To analyse its clinical significance, 10 infants under 1 year of age presenting with Down's syndrome and the morphological picture of acute myelogenous leukaemia were reviewed. 3 of these children had true AML leading to death after 2, 8 and 11 months. In the other 7 children the diagnosis TMD was suggested as spontaneous or in one case interferon-induced remission occurred within 4 to 25 weeks after diagnosis. The interferon-treated patient died of SIDS at the age of 11 months. Another one of the TMD children developed fatal erythroleukaemia at the age of 2 years. Regarding initial clinical and haematological parameters, TMD was indistinguishable from true congenital leukaemie. In all patients classification according to the FAB criteria was difficult, as mainly undifferentiated or poorly differentiated myeloid blasts were seen, sometimes with erythro- or megakaryocytic features. Because of the difficulties in the differential diagnosis of TMD and true AML it is recommended to delay specific cytostatic therapy in neonates with Down's syndrome, until definite progression of the leukaemic process is observed or cytogenetic analyses suggesting true AML are available.
Nik Siti Fatimah Mohamed
Full Text Available Introduction: The association of myasthenia gravis (MG with other autoimmune diseases including autoimmune thyroid disease (ATD is well recognised, although rare. The occurrence of both diseases can occur in two ways: either disease preceding the other, or concurrently. The presentation of MG in association with ATD can range from ocular to generalised disease. Case Summary: A 26-year-old Malay female with persistent hyperthyroidism secondary to Hashimoto’s thyroiditis in multinodular goitre was diagnosed with generalised MG after 2 years. She presented with right eye ptosis (ocular and difficulty in swallowing and chewing (bulbar. The diagnosis of MG was confirmed by fatigability testing, electromyography and the presence of AChR antibodies. Her symptoms showed improvement with pyridostigmine (Mestinon 60 mg 6-hourly. Her antithyroid drug was tapered down according to her thyroid function test. Throughout a year of follow-ups, her hyperthyroidism and fatigability symptoms improved with treatment. She was later counselled for total thyroidectomy and thymectomy. Conclusion: Myasthenia gravis and hyperthyroidism may present with similar symptoms such as dysphagia due to neuromuscular weakness or fatigue. When the diseases occur together, one of the diagnoses may be missed. Therefore, the occurrence of new symptoms in a patient with underlying ATD should should trigger the early identification of other autoimmune diseases by primary care doctors.
Se Jung Oh
Full Text Available Purpose : The neonatal screening test for homocystinuria primarily measures methionine by using a dried blood specimen. We investigated the incidence and clinical manifestations of homocystinuria, isolated hypermethioninemia, and transient hypermethioninemia among patients with hypermethioninemia on a neonatal screening test. Methods : We performed a retrospective study of 58 patients transferred to Shoonchunhyang Hospital because of hypermethioninemia on a neonatal screening test between January 1996 and August 2009. We analyzed the level of amino acid from plasma and urine, as well as blood homocysteine. Results : Almost half of the 58 patients were identified as normal. Whereas only 3 (5.1% patients were identified as having homocystinuria, about 20.7% (12 cases of the patients had isolated hypermethioninemia. The ages of these two groups at initial detection of hypermethioninemia on plasma amino acid analysis were 50.0¡?#?2.5; days and 34.9¡?#?3.5; days, respectively. Both groups were put on diets, and they showed a normal developmental course as a result of early diagnosis and treatment. Conclusion : Hypermethioninemia without homocystinuria, referred to as isolated hypermethioninemia, was also detected. Thus, the impact of hypermethioninemia on a neonatal screening test should be carefully evaluated through analysis of amino acid levels from blood and urine, and we need to detect and treat an early stage of isolated hypermethioninemia as well as homocystinuria.
Losen, Mario; Labrijn, Aran F; van Kranen-Mastenbroek, Vivianne H; Janmaat, Maarten L; Haanstra, Krista G; Beurskens, Frank J; Vink, Tom; Jonker, Margreet; 't Hart, Bert A; Mané-Damas, Marina; Molenaar, Peter C; Martinez-Martinez, Pilar; van der Esch, Eline; Schuurman, Janine; de Baets, Marc H; Parren, Paul W H I
Autoantibodies against ion channels are the cause of numerous neurologic autoimmune disorders. Frequently, such pathogenic autoantibodies have a restricted epitope-specificity. In such cases, competing antibody formats devoid of pathogenic effector functions (blocker antibodies) have the potential to treat disease by displacing autoantibodies from their target. Here, we have used a model of the neuromuscular autoimmune disease myasthenia gravis in rhesus monkeys (Macaca mulatta) to test the therapeutic potential of a new blocker antibody: MG was induced by passive transfer of pathogenic acetylcholine receptor-specific monoclonal antibody IgG1-637. The effect of the blocker antibody (IgG4Δhinge-637, the hinge-deleted IgG4 version of IgG1-637) was assessed using decrement measurements and single-fiber electromyography. Three daily doses of 1.7 mg/kg IgG1-637 (cumulative dose 5 mg/kg) induced impairment of neuromuscular transmission, as demonstrated by significantly increased jitter, synaptic transmission failures (blockings) and a decrease in the amplitude of the compound muscle action potentials during repeated stimulations (decrement), without showing overt symptoms of muscle weakness. Treatment with three daily doses of 10 mg/kg IgG4Δhinge-637 significantly reduced the IgG1-637-induced increase in jitter, blockings and decrement. Together, these results represent proof-of principle data for therapy of acetylcholine receptor-myasthenia gravis with a monovalent antibody format that blocks binding of pathogenic autoantibodies.
Full Text Available Summary: Pluripotent stem cells (PSCs offer unprecedented opportunities for disease modeling and personalized medicine. However, PSC-derived cells exhibit fetal-like characteristics and remain immature in a dish. This has emerged as a major obstacle for their application for late-onset diseases. We previously showed that there is a neonatal arrest of long-term cultured PSC-derived cardiomyocytes (PSC-CMs. Here, we demonstrate that PSC-CMs mature into adult CMs when transplanted into neonatal hearts. PSC-CMs became similar to adult CMs in morphology, structure, and function within a month of transplantation into rats. The similarity was further supported by single-cell RNA-sequencing analysis. Moreover, this in vivo maturation allowed patient-derived PSC-CMs to reveal the disease phenotype of arrhythmogenic right ventricular cardiomyopathy, which manifests predominantly in adults. This study lays a foundation for understanding human CM maturation and pathogenesis and can be instrumental in PSC-based modeling of adult heart diseases. : Pluripotent stem cell (PSC-derived cells remain fetal like, and this has become a major impediment to modeling adult diseases. Cho et al. find that PSC-derived cardiomyocytes mature into adult cardiomyocytes when transplanted into neonatal rat hearts. This method can serve as a tool to understand maturation and pathogenesis in human cardiomyocytes. Keywords: cardiomyocyte, maturation, iPS, cardiac progenitor, neonatal, disease modeling, cardiomyopathy, ARVC, T-tubule, calcium transient, sarcomere shortening
MARCIO F. DE CARVALHO
Full Text Available Os autores descrevem o caso de uma mulher branca de 24 anos de idade admitida com lupus eritematoso sistêmico (com 4 anos de evolução de doença e início recente de miastenia gravis. São discutidos os principais diagnósticos diferenciais para a fraqueza muscular e a fadiga apresentadas por esta paciente. Uma revisão de literatura abordando a associação de miastenia gravis e lupus eritematoso é feita, com ênfase às características clínicas desses pacientes e ao papel do timoma e timectomia no desenvolvimento de lupus eritematoso em pacientes previamente miastênicos.We report the case of a 24-year-old white woman admitted with a four year diagnosis of systemic lupus erythematosus and the recent onset of myasthenia gravis discussing the main differential diagnosis of weakness and fatigue in this patient. A review of literature approaching the association of myasthenia gravis and systemic lupus erythematosus is also done with emphasis on the clinical characteristics of these patients and the role of thymoma and thymectomy in the development of systemic lupus erythematosus in myasthenic patients.
Saoudi, A; Bernard, I; Hoedemaekers, A
Experimental autoimmune myasthenia gravis (EAMG) is a T cell-dependent, Ab-mediated autoimmune disease induced in rats by a single immunization with acetylcholine receptor (AChR). Although polarized Th1 responses have been shown to be crucial for the development of mouse EAMG, the role of Th cell...
Renata Mota Mamede de Carvallo
Full Text Available Objective: The aim of the present investigation was to check Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests applied together in regular nurseries and Newborn Intensive Care Units (NICU, as well as to describe and compare the results obtained in both groups. Methods: We tested 150 newborns from regular nurseries and 70 from NICU. Rresults: The newborn hearing screening results using Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response tests could be applied to all babies. The “pass” result for the group of babies from the nursery was 94.7% using Transient Evoked Otoacoustic Emissions and 96% using Automatic Auditory Brainstem Response. The newborn intensive care unit group obtained 87.1% on Transient Evoked Otoacoustic Emissions and 80% on the Automatic Auditory Brainstem Response, and there was no statistical difference between the procedures when the groups were evaluated individually. However, comparing the groups, Transient Evoked Otoacoustic Emissions were presented in 94.7% of the nursery babies and in 87.1% in the group from the newborn intensive care unit. Considering the Automatic Auditory Brainstem Response, we found 96 and 87%, respectively. Cconclusions: Transient Evoked Otoacoustic Emissions and Automatic Auditory Brainstem Response had similar “pass” and “fail” results when the procedures were applied to neonates from the regular nursery, and the combined tests were more precise to detect hearing impairment in the newborn intensive care unit babies.
Mulkey, Sarah B.; Swearingen, Christopher J.
Neonatal neurology is a growing sub-specialty area. Given the considerable amount of neurologic problems present in the neonatal intensive care unit, a neurologist with expertise in neonates is becoming more important. We sought to evaluate the change in neurologic care in the neonatal intensive care unit at our tertiary care hospital by having a dedicated neonatal neurologist. The period post-neonatal neurologist showed a greater number of neurology consultations (Pneurology encounters per patient (Pneurology became part of the multi-disciplinary team providing focused neurologic care to newborns. PMID:23271754
Wang, Zhen; Yan, Yaping
Myasthenia gravis (MG) and neuromyelitis optica (NMO) are autoimmune channelopathies of the peripheral neuromuscular junction (NMJ) and central nervous system (CNS) that are mainly mediated by humoral immunity against the acetylcholine receptor (AChR) and aquaporin-4 (AQP4), respectively. The diseases share some common features, including genetic predispositions, environmental factors, the breakdown of tolerance, the collaboration of T cells and B cells, imbalances in T helper 1 (Th1)/Th2/Th17/regulatory T cells, aberrant cytokine and antibody secretion, and complement system activation. However, some aspects of the immune mechanisms are unique. Both targets (AChR and AQP4) are expressed in the periphery and CNS, but MG mainly affects the NMJ in the periphery outside of CNS, whereas NMO preferentially involves the CNS. Inflammatory cells, including B cells and macrophages, often infiltrate the thymus but not the target—muscle in MG, whereas the infiltration of inflammatory cells, mainly polymorphonuclear leukocytes and macrophages, in NMO, is always observed in the target organ—the spinal cord. A review of the common and discrepant characteristics of these two autoimmune channelopathies may expand our understanding of the pathogenic mechanism of both disorders and assist in the development of proper treatments in the future. PMID:29312313
Full Text Available The relationship between myasthenia gravis (MG and other autoimmune disorders like hyperthyroidism is well known. It may manifest earlier, concurrently orafter the appearance of MG. The effect of treatment of hyperthyroidism on the control of MG is variable. There may be resolution or conversely, deterioration of the symptoms also. We present a patient who was diagnosed to be hyperthyroid two and half years before the appearance of myasthenic symptoms. Pharmacotherapy for three months neither improved the myasthenic symptoms nor the thyroid function tests. Thymectomy resulted in control of MG as well as hyperthyroidism. In conclusion, effective control of hyperthyroidism in the presence of MG may be difficult. The authors opine that careful peri-operative management of thymectomy is possible in a hyperthyroid state.
Datt, Vishnu; Tempe, Deepak K; Singh, Baljit; Tomar, Akhlesh S; Banerjee, Amit; Dutta, Devesh; Bhandari, Hricha
The relationship between myasthenia gravis (MG) and other autoimmune disorders like hyperthyroidism is well known. It may manifest earlier, concurrently or after the appearance of MG. The effect of treatment of hyperthyroidism on the control of MG is variable. There may be resolution or conversely, deterioration of the symptoms also. We present a patient who was diagnosed to be hyperthyroid two and half years before the appearance of myasthenic symptoms. Pharmacotherapy for three months neither improved the myasthenic symptoms nor the thyroid function tests. Thymectomy resulted in control of MG as well as hyperthyroidism. In conclusion, effective control of hyperthyroidism in the presence of MG may be difficult. The authors opine that careful peri-operative management of thymectomy is possible in a hyperthyroid state.
Cheung, Evelyn Ning Man; George, Susan R.; Andrade, Danielle M.; Chow, Eva W. C.; Silversides, Candice K.; Bassett, Anne S.
Purpose Hypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome. Methods We used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability. Results The model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate- to-severe intellectual disability with other factors such as major structural brain malformations in this sample. Conclusion The results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions. PMID:23765047
Tuzun, Erdem; Berrih-Aknin, Sonia; Brenner, Talma; Kusner, Linda L; Le Panse, Rozen; Yang, Huan; Tzartos, Socrates; Christadoss, Premkumar
Myasthenia gravis (MG) is an autoimmune disorder characterized by generalized muscle weakness due to neuromuscular junction (NMJ) dysfunction brought by acetylcholine receptor (AChR) antibodies in most cases. Although steroids and other immunosuppressants are effectively used for treatment of MG, these medications often cause severe side effects and a complete remission cannot be obtained in many cases. For pre-clinical evaluation of more effective and less toxic treatment methods for MG, the experimental autoimmune myasthenia gravis (EAMG) induced by Torpedo AChR immunization has become one of the standard animal models. Although numerous compounds have been recently proposed for MG mostly by using the active immunization EAMG model, only a few have been proven to be effective in MG patients. The variability in the experimental design, immunization methods and outcome measurements of pre-clinical EAMG studies make it difficult to interpret the published reports and assess the potential for application to MG patients. In an effort to standardize the active immunization EAMG model, we propose standard procedures for animal care conditions, sampling and randomization of mice, experimental design and outcome measures. Utilization of these standard procedures might improve the power of pre-clinical EAMG experiments and increase the chances for identifying promising novel treatment methods that can be effectively translated into clinical trials for MG. Copyright © 2015 Elsevier Inc. All rights reserved.
Full Text Available Osteopoikilosis is an uncommon hereditary dysplasia of skeleton characterized by small sclerotic foci clustered mainly in periarticular osseus regions. The radiographic pattern is pathognomonic. The disease can be a result of the loss-of-function mutations in LEMD3 – the gene responsible for bone density which can influence also on the expression of transforming growth factor β1 (TGF-β1 signalling. TGF-β1 is a key mediator of fibrosis and a modulator of immune responses. Patients with osteopoikilosis demonstrate a higher incidence of keloid formation and autoimmune diseases. In the presented case osteopoikilosis was associated with keloids formation and autoimmune diseases: rheumatoid arthritis, myasthenia, Graves’ disease and megaloblastic anaemia.
Morita Maria da Penha A.
Full Text Available Myasthenia gravis (MG in childhood is rare comprising 10 to 20 % of all myasthenic patients. We studied 18 patients with MG whose first symptoms started from 1 to 12 years of age, followed at the Department of Neurology of the UNIFESP-EPM, from January 1983 to August 1997. There were 10 girls and 8 boys (1.2:1. Eleven patients (61% presented moderate or severe generalized disease and 4 (22% had at least one myasthenic crisis. EMG with supramaximal repetitive nerve stimulation was diagnostic in 8 (47% out of 17 patients, and chest CT was normal in 14 patients. Seropositivity to acetylcholine receptor antibodies was found in 81.6% (9 out of 11 tested and the levels had no relation to clinical severity. Nine out of 16 patients (56% worsened with pyridostigmine alone and were treated with prednisone. Four out of those nine continued worsening despite steroids and were subjected to thymectomy (all showed thymic lymphoid follicular hyperplasia. Three patients (75% improved markedly after thymectomy and one (25% worsened, eventually getting better with intravenous immunoglobulin and oral azathioprine. MG treatment, using all resources available, has to be individualized for each child.
Thomas, Erica; Manji, Karim; Mpembeni Rose
Failure to thrive or growth failure is an important feature of problems prevalent in the neonate. It remains one of the greatest challenges for the practicing pediatrician and it is a common pathway or outcome of several different underlaying infant and maternal conditions. To determine the prevalence, possible causes and early neonatal outcome of failure to thrive among young infants admitted to the Neonatal Unit in this hospital. A cross-sectional descriptive hospital based study, was carried for 10 months from April 2001 to January 2002 at the Neonatal Unit at Muhimbili National Hospital. (author)
Full Text Available The objective of this study is to determine risk factors causing increase in very low birth way (VLBW neonatal mortality. The medical files of all neonates weighing ≤1500 g, born in Vali-e-Asr hospital (2001-2004 were studied. Two groups of neonates (living and dead were compared up to the time of hospital discharge or death. A total of 317 neonates were enrolled. A meaningful relationship existed between occurrence of death and low gestational age (P=0.02, low birth weight, lower than 1000 g (P=0.001, Apgar score <6 at 5th minutes (P=0.001, resuscitation at birth (P=0.001, respiratory distress syndrome (P=0.001 need for mechanical ventilation (P=0.001, neurological complications (P=0.001 and intraventricular hemorrhage (P=0.001. Regression analysis indicated that each 250 g weight increase up to 1250 g had protective effect, and reduced mortality rate. The causes of death of those neonates weighting over 1250 g should be sought in factors other than weight. Survival rate was calculated to be 80.4% for neonates weighing more than 1000 g. The most important high risk factors affecting mortality of neonates are: low birth weight, need for resuscitation at birth, need for ventilator use and intraventricular hemorrhage.
Pawan Kumar Jain
Full Text Available Myasthenia gravis is a chronic autoimmune disease affecting voluntary skeletal muscles. The altered sensitivity of acetylcholine receptors to muscle relaxants and concomitant treatment with anticholinesterase in these patients affect their anaesthetic management. Patients who have undergone bowel anastomosis and are on regular anticholinesterase treatment are susceptible to anastomotic leaks. We report successful anaesthetic management of class I myasthenic patient with coexisting small bowel intussusception operated for jejuno-ileal anastomoses using regional, inhalational and intravenous (i.v anaesthesia based on train of four responses, and avoiding the use of reversal (anticholinesterase.
Hattori, Kazuki; Shirasawa, Nobuyuki; Suzuki, Hikaru; Otsuka, Takanobu; Wada, Ikuo; Yashiro, Takashi; Herbert, Damon C; Soji, Tsuyoshi; Hashitani, Hikaru
In the transitional zone of the rat anterior pituitary, spontaneous and LHRH-induced Ca(2+) dynamics were visualized using fluo-4 fluorescence Ca(2+) imaging. A majority of cells exhibited spontaneous Ca(2+) transients, while small populations of cells remained quiescent. Approximately 70% of spontaneously active cells generated fast, oscillatory Ca(2+) transients that were inhibited by cyclopiazonic acid (10 μm) but not nicardipine (1 μm), suggesting that Ca(2+) handling by endoplasmic reticulum, but not Ca(2+) influx through voltage-dependent L-type Ca(2+) channels, plays a fundamental role in their generation. In the adult rat anterior pituitary, LHRH (100 μg/ml) caused a transient increase in the Ca(2+) level in a majority of preparations taken from the morning group rats killed between 0930 h and 1030 h. However, the second application of LHRH invariably failed to elevate Ca(2+) levels, suggesting that the long-lasting refractoriness to LHRH stimulation was developed upon the first challenge of LHRH. In contrast, LHRH had no effect in most preparations taken from the afternoon group rats euthanized between 1200 h and 1400 h. In the neonatal rat anterior pituitary, LHRH caused a suppression of spontaneous Ca(2+) transients. Strikingly, the second application of LHRH was capable of reproducing the suppression of Ca(2+) signals, indicating that the refractoriness to LHRH had not been established in neonatal rats. These results suggest that responsiveness to LHRH has a long-term refractoriness in adult rats, and that the physiological LHRH surge may be clocked in the morning. Moreover, LHRH-induced excitation and associated refractoriness appear to be incomplete in neonatal rats and may be acquired during development.
Ana Campo González
Full Text Available INTRODUCCIÓN. La mayoría de las veces la ictericia en el recién nacido es un hecho fisiológico, causado por una hiperbilirrubinemia de predominio indirecto, secundario a inmadurez hepática e hiperproducción de bilirrubina. El objetivo de este estudio fue determinar el comportamiento de la hiperbilirrubinemia neonatal en el Hospital Docente Ginecoobstétrico de Guanabacoa en los años 2007 a 2009. MÉTODOS. Se realizó un estudio descriptivo y retrospectivo de 173 recién nacidos que ingresaron al Departamento de Neonatología con diagnóstico de hiperbilirrubinemia agravada. RESULTADOS. La incidencia de hiperbilirrubinemia neonatal agravada fue del 3,67 % y predominó en hermanos con antecedentes de ictericia (56,65 %. El tiempo de aparición fue de 48 a 72 h (76,87 % y entre los factores agravantes se hallaron el nacimiento pretérmino y el bajo peso al nacer. La mayoría de los pacientes fueron tratados con luminoterapia (90,17 %. CONCLUSIÓN. La hiperbilirrubinemia neonatal agravada constituye un problema de salud. Los factores agravantes son la prematuridad y el bajo peso al nacer. La luminoterapia es una medida terapéutica eficaz para su tratamiento.INTRODUCTION. Most of times jaundice in newborn is a physiological fact due to hyperbilirubinemia of indirect predominance, secondary to liver immaturity and to bilirubin hyperproduction. The aim of present of present study was to determine the behavior of neonatal hyperbilirubinemia in the Gynecology and Obstetrics Teaching Hospital of Guanabacoa municipality from 2007 to 2009. METHODS. A retrospective and descriptive study was conducted in 173 newborn patients admitted in the Neonatology Department diagnosed with severe hyperbilirubinemia. RESULTS. The incidence of severe neonatal hyperbilirubinemia was of 3,67% with predominance in brothers with a history of jaundice (56,65%. The time of appearance was of 48 to 72 hrs (76,87% and among the aggravating factors were the preterm birth and
administración endovenosa de gamma globulina.Juvenile myasthenia gravis is a chronic autoimmune disorder which occurs when serum antibodies combine with nicotinic acetylcholine receptors at the muscle membrane of the motor endplate imparing the neuromuscular transmission. It results in early muscle fatigability with progression to a complete paralysis during repetitive muscle contraction (movements or steady muscle contraction (postures, and less common persistent paralysis at rest. The cranial nerves, mainly the one innervating the extraoccular and palpebral levator, are the most susceptible to permanent weakness and paralysis at rest. Initial clinical presentations are generalized, ocular and respiratory forms. The diagnosis is suspected through medical history of abnormal fatigability and corroborated by physical examination, repetitive nerve stimulation of an affected but not complete paralyzed muscle, correction of fatigability by the intravenous administration of acetylcholine esterase inhibitors, and by the presence of serum acetylcholine receptors antibodies (ACRA. The long term treatment is symptomatic (acetylcholine inhibitors and etiopathogenic (immunosupresor drugs, plasmapheresis, intravenous gamma globulin and thymectomy. Spontaneous or post symptomatic and etiopathogenic treatment remissions occur from 1 to 10 years. Fatality is rare but children are at high risk during myasthenia crisis.
Fernández-López, David; Faustino, Joel; Klibanov, Alexander L; Derugin, Nikita; Blanchard, Elodie; Simon, Franziska; Leib, Stephen L; Vexler, Zinaida S
Perinatal stroke leads to significant morbidity and long-term neurological and cognitive deficits. The pathophysiological mechanisms of brain damage depend on brain maturation at the time of stroke. To understand whether microglial cells limit injury after neonatal stroke by preserving neurovascular integrity, we subjected postnatal day 7 (P7) rats depleted of microglial cells, rats with inhibited microglial TGFbr2/ALK5 signaling, and corresponding controls, to transient middle cerebral artery occlusion (tMCAO). Microglial depletion by intracerebral injection of liposome-encapsulated clodronate at P5 significantly reduced vessel coverage and triggered hemorrhages in injured regions 24 h after tMCAO. Lack of microglia did not alter expression or intracellular redistribution of several tight junction proteins, did not affect degradation of collagen IV induced by the tMCAO, but altered cell types producing TGFβ1 and the phosphorylation and intracellular distribution of SMAD2/3. Selective inhibition of TGFbr2/ALK5 signaling in microglia via intracerebral liposome-encapsulated SB-431542 delivery triggered hemorrhages after tMCAO, demonstrating that TGFβ1/TGFbr2/ALK5 signaling in microglia protects from hemorrhages. Consistent with observations in neonatal rats, depletion of microglia before tMCAO in P9 Cx3cr1(GFP/+)/Ccr2(RFP/+) mice exacerbated injury and induced hemorrhages at 24 h. The effects were independent of infiltration of Ccr2(RFP/+) monocytes into injured regions. Cumulatively, in two species, we show that microglial cells protect neonatal brain from hemorrhage after acute ischemic stroke. Copyright © 2016 the authors 0270-6474/16/362881-13$15.00/0.
Lazaridis, Konstantinos; Dalianoudis, Ioannis; Baltatzidi, Vasiliki; Tzartos, Socrates J
Myasthenia gravis (MG) is caused by autoantibodies, the majority of which target the muscle acetylcholine receptor (AChR). Plasmapheresis and IgG-immunoadsorption are useful therapy options, but are highly non-specific. Antigen-specific immunoadsorption would remove only the pathogenic autoantibodies, reducing the possibility of side effects while maximizing the benefit. We have extensively characterized such adsorbents, but in vivo studies are missing. We used rats with experimental autoimmune MG to perform antigen-specific immunoadsorptions over three weeks, regularly monitoring symptoms and autoantibody titers. Immunoadsorption was effective, resulting in a marked autoantibody titer decrease while the immunoadsorbed, but not the mock-treated, animals showed a dramatic symptom improvement. Overall, the procedure was found to be efficient, suggesting the subsequent initiation of clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.
Ebner, Nina; Rohrmeister, Klaudia; Winklbaur, Bernadette; Baewert, Andjela; Jagsch, Reinhold; Peternell, Alexandra; Thau, Kenneth; Fischer, Gabriele
Neonates born to opioid-maintained mothers are at risk of developing neonatal abstinence syndrome (NAS), which often requires pharmacological treatment. This study examined the effect of opioid maintenance treatment on the incidence and timing of NAS, and compared two different NAS treatments (phenobarbital versus morphine hydrochloride). Fifty-three neonates born to opioid-maintained mothers were included in this study. The mothers received methadone (n=22), slow-release oral morphine (n=17) or buprenorphine (n=14) throughout pregnancy. Irrespective of maintenance treatment, all neonates showed APGAR scores comparable to infants of non-opioid dependent mothers. No difference was found between the three maintenance groups regarding neonatal weight, length or head circumference. Sixty percent (n=32) of neonates required treatment for NAS [68% in the methadone-maintained group (n=15), 82% in the morphine-maintained group (n=14), and 21% in the buprenorphine-maintained group (n=3)]. The mean duration from birth to requirement of NAS treatment was 33 h for the morphine-maintained group, 34 h for the buprenorphine-maintained group and 58 h for the methadone-maintained group. In neonates requiring NAS treatment, those receiving morphine required a significantly shorter mean duration of treatment (9.9 days) versus those treated with phenobarbital (17.7 days). Results suggest that morphine hydrochloride is preferable for neonates suffering NAS due to opioid withdrawal.
Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study
Howard, James F.; Utsugisawa, Kimiaki; Benatar, Michael; Murai, Hiroyuki; Barohn, Richard J.; Illa, Isabel; Jacob, Saiju; Vissing, John; Burns, Ted M.; Kissel, John T.; Muppidi, Srikanth; Nowak, Richard J.; O'Brien, Fanny; Wang, Jing-Jing; Mantegazza, Renato; Mazia, Claudio Gabriel; Wilken, Miguel; Ortea, Carolina; Saba, Juliet; Rugiero, Marcelo; Bettini, Mariela; Vidal, Gonzalo; Garcia, Alejandra Dalila; Lamont, Phillipa; Leong, Wai-Kuen; Boterhoven, Heidi; Fyfe, Beverly; Roberts, Leslie; Jasinarachchi, Mahi; Willlems, Natasha; Wanschitz, Julia; Löscher, Wolfgang; de Bleecker, Jan; van den Abeele, Guy; de Koning, Kathy; de Mey, Katrien; Mercelis, Rudy; Wagemaekers, Linda; Mahieu, Delphine; van Damme, Philip; Smetcoren, Charlotte; Stevens, Olivier; Verjans, Sarah; D'Hondt, Ann; Tilkin, Petra; Alves de Siqueira Carvalho, Alzira; Hasan, Rosa; Dias Brockhausen, Igor; Feder, David; van der Kooi, Anneke
Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with
Walker, Suellen M
Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444
Jenster, Meike; Bonifacio, Sonia L; Ruel, Theodore; Rogers, Elizabeth E; Tam, Emily W; Partridge, John Colin; Barkovich, Anthony James; Ferriero, Donna M; Glass, Hannah C
Perinatal infection may potentiate brain injury among children born preterm. The objective of this study was to examine whether maternal and/or neonatal infection are associated with adverse outcomes among term neonates with encephalopathy. This study is a cohort study of 258 term newborns with encephalopathy whose clinical records were examined for signs of maternal infection (chorioamnionitis) and infant infection (sepsis). Multivariate regression was used to assess associations between infection, pattern, and severity of injury on neonatal magnetic resonance imaging, as well as neurodevelopment at 30 mo (neuromotor examination, or Bayley Scales of Infant Development, second edition mental development index encephalopathy, chorioamnionitis was associated with a lower risk of brain injury and adverse outcomes, whereas signs of neonatal sepsis carried an elevated risk. The etiology of encephalopathy and timing of infection and its associated inflammatory response may influence whether infection potentiates or mitigates injury in term newborns.
Pastor Durán, Xavier
PROTOCOLOS TERAPEUTICOS. TUBERCULOSIS NEONATAL 1. CONCEPTO La tuberculosis neonatal es la infección del recién nacido producida por el bacilo de Koch. Es una situación rara pero grave que requiere un diagnóstico precoz y un tratamiento enérgico..
Álvarez-Cordovés, M M; Mirpuri-Mirpuri, P G; Pérez-Monje, A
Myasthenia gravis is an autoimmune disorder of neuromuscular transmission involving the production of autoantibodies directed against skeletal muscle receptors, in most cases of acetylcholine. Clinically it is characterized by the appearance of muscle weakness after prolonged activity, which tends to recover after a period of rest, or administration of acetylcholinesterase inhibitors. It is a relatively rare disease, although the prevalence has increased by improved diagnosis and increased longevity of the population. The diagnosis can be based on evidence after it is suspected using pharmacological, immunological or electrophysiology tests. Treatment can be divided into: symptomatic, short term and long term. We report the case of a patient who complained of diplopia, this muscle weakness being the most common initial symptom of the disease. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.
Full Text Available Circulating antibodies of the acetylcholine receptor (AchRAb are detectable in most patients with generalized myasthenia gravis (MG. A newly discovered antibody against muscle-specific kinase (MuSKAb has been detected in 40–70% of AchRAb-negative MG patients. We report a series of Taiwanese MuSKAb-positive patients, and compare their clinical features with MuSKAb-negative patients and also with MuSKAb-positive Caucasians. Five out of 44 seronegative generalized MG patients (11.4% were positive for MuSKAb. Patients with MuSKAb tended to have severe disability and bulbar involvement, and more often experienced crisis or impending crisis. Although all of these patients showed an initial response to immunosuppressant therapy, they had greater disability at follow-up. The clinical features of Taiwanese MuSKAb-positive patients were not different from those of Caucasians, except for a lower prevalence.
Liu, Cheng-wu; Luo, Meng; Mei, Jian-dong; Zhu, Yun-ke; Pu, Qiang; Ma, Lin; Che, Guo-wei; Lin, Yi-dan; Wu, Zhu; Wang, Yun; Kou, Ying-li; Liu, Lun-xu
Thymectomy is an established treatment for myasthenia gravis (MG), and video-assisted thoracoscopic surgery (VATS) thymectomy has become an acceptable surgical procedure. This study aimed to compare the results of VATS thymectomy and open thymectomy and to identify the prognostic factors after thymectomy. The clinical data of 187 consecutive thymectomies performed between July 2000 and December 2009 were retrospectively reviewed; 75 open thymectomies and 112 VATS thymectomies. Clinical efficacy and variables influencing outcome were assessed by Kaplan-Meier survival curves and Cox proportional hazards regression analysis. The operative blood loss in the VATS group was significantly less than that in the open group ((62.14 ± 55.43) ml vs. (137.87 ± 165.25) ml, P CSR) was the end point for evaluation of the treatment results. The overall five-year CSR rate was 57.5%. Two good prognostic factors were identified; preoperative prescription of anticholinesterase alone (P = 0.035) and non-thymomatous MG (P = 0.003). The five-year CSR rate of the ocular type of MG reached a high level of 67.4%. Thymectomy can achieve good long-term CSR in MG, and VATS is an ideal alternative method. High-dose prescription of anticholinesterase and the advanced stage by Myasthenia Gravis Foundation of America (MGFA) classification have higher risks of postoperative crisis. Preoperative prescription of anticholinesterase alone and non-thymomatous MG are good prognostic factors. Thymectomy should also be considered for the ocular type of MG.
Ana Paula Cordoval da Costa
Full Text Available RESUMO Objetivo: verificar se a porcentagem de recém-nascidos que falharam na triagem auditiva do serviço da Clínica Escola do Centro Universitário de Várzea Grande está dentro do determinado pelos indicadores de qualidade dos serviços de Triagem Auditiva Neonatal. Método: estudo retrospectivo, no qual foram analisados os resultados dos exames de Emissões Otoacústicas Transientes realizados no período de Outubro de 2013 a Agosto de 2014, em um serviço gratuito de triagem auditiva neonatal opcional do setor privado de uma universidade da cidade de Várzea Grande-Mato Grosso, Brasil. Compuseram a amostra 251 participantes, subdivididos em dois grupos: grupo de baixo risco composto por 210 participantes, sendo 100 do gênero feminino e 110 do masculino e; grupo de alto risco composto por 41 participantes, sendo 17 do gênero feminino e 24 do masculino. Resultados: foram analisados os resultados da triagem auditiva obtidas com o teste das Emissões Otoacústicas Transientes sendo que no grupo de baixo risco 39,52% passaram, 4,76% falharam e 55,71% não compareceram ao serviço para finalização da triagem. Já no grupo de alto risco, 48,78% passaram, 14,63% falharam e 36,59% não compareceram ao serviço para finalização da triagem, conforme demonstrado nas Tabelas 1 e 2. Conclusão: a porcentagem de indivíduos que falharam na triagem auditiva neonatal pelo serviço avaliado está acima do preconizado pela literatura.
Full Text Available Objective To compare the sensitivity and specificity of ice test, neostigmine test and single fiber electromyography (SFEMG in the diagnosis of ocular myasthenia gravis (OMG, so as to establish an appropriate process for the diagnosis of OMG. Methods A total of 116 patients with newly onset ptosis and/or diplopia were detected by ice test, neostigmine test and SFEMG. Patients were followed up for 6 months to observe the disease changes and experimental treatment effects. Results Apart from patients whose diagnosis was in doubt or lost to follow - up, and who were diagnosed as generalized myasthenia gravis (GMG, the definite diagnosis was finally made in 81 patients, including 21 OMG patients and 60 patients with ptosis and/or diplopia caused by other diseases. The sensitivity of ice test for diagnosis of OMG was 95.24% (20/21, and specificity was 98.33%(59/60. The sensitivity of neostigmine test for diagnosis of OMG was 90.48% (19/21, and specificity was 85% (51/60. The sensitivity of SFEMG for diagnosis of OMG was 95.24% (20/21, and specificity was 80% (48/60. Among 3 tests, only specificity was found significant difference (χ2 = 5.232, P = 0.022. The specificity of ice test was better than that of neostigmine test (χ2 = 5.707, P = 0.017 and SFEMG (χ2 = 6.023, P = 0.014. Conclusions The ice test achieved high sensitivity and specificity in the diagnosis of OMG. The combination of ice test, neostigmine test and SFEMG may have important clinical value for the early diagnosis of OMG. DOI: 10.3969/j.issn.1672-6731.2016.10.008
Ono, K.; Akahane, K.; Aota, T.; Hada, M.; Takano, Y.; Kai, M.; Kusama, T
The aim of this study was to investigate the frequency and type of X ray examinations performed on neonates classified according to their birth weight in a neonatal intensive care unit (NICU). In this study, the radiology records of 2408 neonates who were admitted to the NICU of Oita Prefectural Hospital between January 1994 and September 1999 were investigated. This study revealed that the neonates with earlier gestational ages and lower birth weights required longer NICU stays and more frequent X ray examinations made using a mobile X ray unit. The average number of X ray examinations performed on neonates of less than 750 g birth weight was 26 films per neonate. In regard to computed tomography and fluoroscopy, no significant relationship was found between the birth weight and number of X rays. This study revealed that the entrance-surface dose per neonate was dependent upon the birth weight, while the maximum dose was not dependent upon the birth weight. The average neonatal dose in the NICU was predominantly from computed tomography and fluoroscopy. The individual dose varied widely among neonates. (author)
Ono, K.; Akahane, K.; Aota, T.; Hada, M.; Takano, Y.; Kai, M.; Kusama, T.
The aim of this study was to investigate the frequency and type of X ray examinations performed on neonates classified according to their birth weight in a neonatal intensive care unit (NICU). In this study, the radiology records of 2408 neonates who were admitted to the NICU of Oita Prefectural Hospital between January 1994 and September 1999 were investigated. This study revealed that the neonates with earlier gestational ages and lower birth weights required longer NICU stays and more frequent X ray examinations made using a mobile X ray unit. The average number of X ray examinations performed on neonates of less than 750 g birth weight was 26 films per neonate. In regard to computed tomography and fluoroscopy, no significant relationship was found between the birth weight and number of X rays. This study revealed that the entrance-surface dose per neonate was dependent upon the birth weight, while the maximum dose was not dependent upon the birth weight. The average neonatal dose in the NICU was predominantly from computed tomography and fluoroscopy. The individual dose varied widely among neonates. (author)
Riccabona, Michael, E-mail: firstname.lastname@example.org
Paediatric and particularly neonatal neurosonography still remains a mainstay of imaging the neonatal brain. It can be performed at the bedside without any need for sedation or specific monitoring. There are a number of neurologic conditions that significantly influence morbidity and mortality in neonates and infants related to the brain and the spinal cord; most of them can be addressed by ultrasonography (US). However, with the introduction of first CT and then MRI, neonatal neurosonography is increasingly considered just a basic first line technique that offers only orienting information and does not deliver much relevant information. This is partially caused by inferior US performance – either by restricted availability of modern equipment or by lack of specialized expertise in performing and reading neurosonographic scans. This essay tries to highlight the value and potential of US in the neonatal brain and briefly touching also on the spinal cord imaging. The common pathologies and their US appearance as well as typical indication and applications of neurosonography are listed. The review aims at encouraging paediatric radiologists to reorient there imaging algorithms and skills towards the potential of modern neurosonography, particularly in the view of efficacy, considering growing economic pressure, and the low invasiveness as well as the good availability of US that can easily be repeated any time at the bedside.
Flick Louise H
Full Text Available Abstract Background Young maternal age has long been associated with higher infant mortality rates, but the role of socioeconomic factors in this association has been controversial. We sought to investigate the relationships between infant mortality (distinguishing neonatal from post-neonatal deaths, socioeconomic status and maternal age in a large, retrospective cohort study. Methods We conducted a population-based cohort study using linked birth-death certificate data for Missouri residents during 1997–1999. Infant mortality rates for all singleton births to adolescent women (12–17 years, n = 10,131; 18–19 years, n = 18,954 were compared to those for older women (20–35 years, n = 28,899. Logistic regression was used to estimate adjusted odds ratios (OR and 95% confidence intervals (CI for all potential associations. Results The risk of infant (OR 1.95, CI 1.54–2.48, neonatal (1.69, 1.24–2.31 and post-neonatal mortality (2.47, 1.70–3.59 were significantly higher for younger adolescent (12–17 years than older (20–34 years mothers. After adjusting for race, marital status, age-appropriate education level, parity, smoking status, prenatal care utilization, and poverty status (indicated by participation in WIC, food stamps or Medicaid, the risk of post-neonatal mortality (1.73, 1.14–2.64 but not neonatal mortality (1.43, 0.98–2.08 remained significant for younger adolescent mothers. There were no differences in neonatal or post-neonatal mortality risks for older adolescent (18–19 years mothers. Conclusion Socioeconomic factors may largely explain the increased neonatal mortality risk among younger adolescent mothers but not the increase in post-neonatal mortality risk.
Qureshi, Umar Amin; Ahmad, Nisar; Rasool, Akhter; Choh, Suhail
Clinical manifestations of adrenal hemorrhage vary depending on the degree and rate of hemorrhage, as well as the amount of adrenal cortex compromised by hemorrhage. We report here a case of neonatal adrenal hemorrhage that presented with late onset neonatal jaundice. The cause of adrenal hemorrhage was birth asphyxia.
Dylag, Andrew M; Mayer, Catherine A; Raffay, Thomas M; Martin, Richard J; Jafri, Anjum; MacFarlane, Peter M
Premature infants are at increased risk for wheezing disorders. Clinically, these neonates experience recurrent episodes of apnea and desaturation often treated by increasing the fraction of inspired oxygen (FIO 2 ). We developed a novel paradigm of neonatal intermittent hypoxia with subsequent hyperoxia overshoots (CIH O/E ) and hypothesized that CIH O/E elicits long-term changes on pulmonary mechanics in mice. Neonatal C57BL/6 mice received CIH O/E , which consisted of 10% O2 (1 min) followed by a transient exposure to 50% FIO 2 , on 10-min repeating cycles 24 h/d from birth to P7. Baseline respiratory mechanics, methacholine challenge, RT-PCR for pro and antioxidants, radial alveolar counts, and airway smooth muscle actin were assessed at P21 after 2-wk room air recovery. Control groups were mice exposed to normoxia, chronic intermittent hyperoxia (CIH E ), and chronic intermittent hypoxia (CIH O ). CIH O/E and CIH E increased airway resistance at higher doses of methacholine and decreased baseline compliance compared with normoxia mice. Lung mRNA for NOX2 was increased by CIH O/E . Radial alveolar counts and airway smooth muscle actin was not different between groups. Neonatal intermittent hypoxia/hyperoxia exposure results in long-term changes in respiratory mechanics. We speculate that recurrent desaturation with hyperoxia overshoot may increase oxidative stress and contribute to wheezing in former preterm infants.
Nowadays nearly 10% of all births in western countries are premature. In the last decade, there has been an increase of 45% in the number of neonates that were born in Israel. At the same time, the survival of neonates, especially those with very low birth weight, VLBW, (less than 1,500 gr), has increased dramatically. Diagnostic radiology plays an important role in the assessment and treatment of neonates requiring intensive care. During their prolonged and complex hospitalization, these infants are exposed to multiple radiographic examinations involving X-ray radiation. The extent of the examinations that the infant undergoes depends on its birth weight, gestational age and its medical problems, where most of the treatment effort is focused especially on VLBW neonates. Most of the diagnostic X-ray examinations taken during the hospitalization of neonates in the neonatal intensive care unit (NICU) consist of imaging of the respiratory and gastrointestinal systems, namely, the chest and abdomen. The imaging process is done using mobile X-ray units located at the NICUs. Due to their long hospitalization periods and complex medical condition, all neonates, and neonates with VLBW in particular, are exposed to a much higher level of diagnostic radiation, compared to normal newborns. The goal of this research was to assess the extent of the exposure of neonates in Israel to X-ray radiation during their hospitalization at the neonatal intensive care unit. Five NICUs, located at different geographical zones in Israel and treating 20% of all newborns in Israel every year, participated in this research. The research was conducted in three phases: Phase I: Collection of information on radiographic techniques and exposure parameters (e.g. kV, mAs, focus to skin distance (FSD), examination borders). 499 X-ray examinations (from 157 neonates) were evaluated for necessary and unnecessary exposure of the neonate's organs to X-ray radiation during these examinations. Phase II
Attia, Mohamed; Maurer, Marie; Robinet, Marieke; Le Grand, Fabien; Fadel, Elie; Le Panse, Rozen; Butler-Browne, Gillian; Berrih-Aknin, Sonia
Myasthenia gravis (MG) is a neuromuscular disease caused in most cases by anti-acetyl-choline receptor (AChR) autoantibodies that impair neuromuscular signal transmission and affect skeletal muscle homeostasis. Myogenesis is carried out by muscle stem cells called satellite cells (SCs). However, myogenesis in MG had never been explored. The aim of this study was to characterise the functional properties of myasthenic SCs as well as their abilities in muscle regeneration. SCs were isolated from muscle biopsies of MG patients and age-matched controls. We first showed that the number of Pax7+ SCs was increased in muscle sections from MG and its experimental autoimmune myasthenia gravis (EAMG) mouse model. Myoblasts isolated from MG muscles proliferate and differentiate more actively than myoblasts from control muscles. MyoD and MyoG were expressed at a higher level in MG myoblasts as well as in MG muscle biopsies compared to controls. We found that treatment of control myoblasts with MG sera or monoclonal anti-AChR antibodies increased the differentiation and MyoG mRNA expression compared to control sera. To investigate the functional ability of SCs from MG muscle to regenerate, we induced muscle regeneration using acute cardiotoxin injury in the EAMG mouse model. We observed a delay in maturation evidenced by a decrease in fibre size and MyoG mRNA expression as well as an increase in fibre number and embryonic myosin heavy-chain mRNA expression. These findings demonstrate for the first time the altered function of SCs from MG compared to control muscles. These alterations could be due to the anti-AChR antibodies via the modulation of myogenic markers resulting in muscle regeneration impairment. In conclusion, the autoimmune attack in MG appears to have unsuspected pathogenic effects on SCs and muscle regeneration, with potential consequences on myogenic signalling pathways, and subsequently on clinical outcome, especially in the case of muscle stress.
Higashi, Yasuto; Ono, Shimato; Yasuda, Takeshi; Morimoto, Kenji; Terao, Akira; Shirabe, Teruo; Yokobayashi, Tsuneo (Kawasaki Medical School, Kurashiki, Okayama (Japan))
We here report on skeletal-muscle CT at the thigh level as studied using a whole-body CT scanner, with special reference to polymyositis (PM) and myasthenia gravis (MG). Early diseased muscles appeared homogenous and were likely to be almost normal. The first sign of muscular atrophy was the appearance of small, patchy or linear, low-density tissues in several muscles. These low-density tissues gradually increased in number until finally the diseased muscles were totally replaced by low-density tissue. These pathological findings were more severe in PM than in MG. There was a maldistribution of low-density tissue in several cases of PM. According to these findings, skeletal-muscle CT was thought to be of great help for the recognition of the general condition of muscles and for the follow-up on the patients. We think skeletal-muscle CT has a very practical application for the better selection of suitable muscular biopsy and EMG sites and for the better clinical interpretation of these findings.
Higashi, Yasuto; Ono, Shimato; Yasuda, Takeshi; Morimoto, Kenji; Terao, Akira; Shirabe, Teruo; Yokobayashi, Tsuneo
We here report on skeletal-muscle CT at the thigh level as studied using a whole-body CT scanner, with special reference to polymyositis (PM) and myasthenia gravis (MG). Early diseased muscles appeared homogenous and were likely to be almost normal. The first sign of muscular atrophy was the apperance of small, patchy or linear, low-density tissues in several muscles. These low-density tissues gradually increased in number until finally the diseased muscles were totally replaced by low-density tissue. These pathological findings were more severe in PM than in MG. There was a maldistribution of low-density tissue in several cases of PM. According to these findings, skeletal-muscle CT was thought to be of great help for the recognition of the general condition of muscles and for the follow-up on the patients. We think skeletal-muscle CT has a very practical application for the better selection of suitable muscular biopsy and EMG sites and for the better clinical interpretation of these findings. (author)
Full Text Available The past 2-3 decades have seen dramatic changes in the approach to pain management in the neonate. These practices started with refuting previously held misconceptions regarding nociception in preterm infants. Although neonates were initially thought to have limited response to painful stimuli, it was demonstrated that the developmental immaturity of the central nervous system makes the neonate more likely to feel pain. It was further demonstrated that untreated pain can have long-lasting physiologic and neurodevelopmental consequences. These concerns have resulted in a significant emphasis on improving and optimizing the techniques of analgesia for neonates and infants. The following article will review techniques for pain assessment, prevention, and treatment in this population with a specific focus on acute pain related to medical and surgical conditions.
Baggi, Fulvio; Mantegazza, Renato; Antozzi, Carlo; Sanders, Donald
Clinical registries may facilitate research on myasthenia gravis (MG) in several ways: as a source of demographic, clinical, biological, and immunological data on large numbers of patients with this rare disease; as a source of referrals for clinical trials; and by allowing rapid identification of MG patients with specific features. Physician-derived registries have the added advantage of incorporating diagnostic and treatment data that may allow comparison of outcomes from different therapeutic approaches, which can be supplemented with patient self-reported data. We report the demographic analysis of MG patients in two large physician-derived registries, the Duke MG Patient Registry, at the Duke University Medical Center, and the INNCB MG Registry, at the Istituto Neurologico Carlo Besta, as a preliminary study to assess the consistency of the two data sets. These registries share a common structure, with an inner core of common data elements (CDE) that facilitate data analysis. The CDEs are concordant with the MG-specific CDEs developed under the National Institute of Neurological Disorders and Stroke Common Data Elements Project. © 2012 New York Academy of Sciences.
Kang, Ki Mun; Choi, Ihl Bohng; Kim, In Ah
Myasthenia Gravis (MG) is relatively rare occuring as one of important autoimmune disease to affect neuromuscular junction. This study was clinically to evaluate total body irradiation (TBI) against two patients including 33-year and 39-year females for chronic MG with thymoma who hospitalized in the St. Mary's Hospital, Catholic University since 1994 as well as who showed no response by thymectomy, immunotherapy and hormonal therapy. TBI designed by the dose of 150-180 cGy consisting of 10 cGy per fraction, three times a week, for 5-6 weeks using linear accelerator of 6 MV. During the treatment of TBI, they did complain acute side effect such as vomiting and also appear improved physical condition from 4-6 weeks after TBI. Through the follow-up period of 18 or 42 months after TBI, they did not have any symptomatic recurrence. Consequently, the results suggest that TBI can be used as an alternative tool for the patients concurrently for MG with thymoma who had been refractory to various conventional therapies like thymectomy, immunotherapy and hormonal therapy
Liu Fugeng; Wei Jiahu; Pan Jishu; Zhou Cheng; Chen Qihang; Yu Jingying; Wu Guogeng; Xu Xianhao
Objective: To evaluate the CT findings of lymphofollicular thymic hyperplasia in adult myasthenia gravis (MG). Methods: The CT findings of thymus area of 134 adult patients with lymphofollicular thymic hyperplasia in MG were reviewed, all of them with surgically and histologically proven diagnosis, and compared with the CT findings of 165 normal subjects. Results: In the group of patient, CT showed enlargement of thymus in 31 patients, 5 patients had nodule or mass ( 3 cm) and 9 patients (6.7%) had normal size thymus with soft-tissue density, it can considered with thymic hyperplasia. The spotty or streak shadow showed in other patients, though it could not be certain diagnosed as thymic hyperplasia, but could not be except it. The thymus area tissue complete replacement by fatty density were not found in patient group. The CT findings of patients had marked difference when compared with group of normal subjects (P<0.01), except the spotty or streak shadows. Conclusion: CT scan is an important method in diagnosing thymic lymphofollicular hyperplasia of MG in adult. (authors)
Kang, Ki Mun; Choi, Ihl Bohng; Kim, In Ah [College of Medicine, Catholic Univ., Seoul (Korea, Republic of)
Myasthenia Gravis (MG) is relatively rare occuring as one of important autoimmune disease to affect neuromuscular junction. This study was clinically to evaluate total body irradiation (TBI) against two patients including 33-year and 39-year females for chronic MG with thymoma who hospitalized in the St. Mary's Hospital, Catholic University since 1994 as well as who showed no response by thymectomy, immunotherapy and hormonal therapy. TBI designed by the dose of 150-180 cGy consisting of 10 cGy per fraction, three times a week, for 5-6 weeks using linear accelerator of 6 MV. During the treatment of TBI, they did complain acute side effect such as vomiting and also appear improved physical condition from 4-6 weeks after TBI. Through the follow-up period of 18 or 42 months after TBI, they did not have any symptomatic recurrence. Consequently, the results suggest that TBI can be used as an alternative tool for the patients concurrently for MG with thymoma who had been refractory to various conventional therapies like thymectomy, immunotherapy and hormonal therapy.
Ali Hossein Zeinalzadeh
Full Text Available Background: Neonatal survival is one of the most important challenges today. Over 99% of neonatal mortalities occur in the developing countries, and epidemiologic studies emphasize on this issue in the developed countries, as well. In this study, we attempted to investigate the causes of neonatal mortality in Taleghani Hospital, Tabriz, Iran.Methods: In this cross-sectional study, we studied causes of neonatal mortality in neonatal intensive care unit (NICU of Taleghani Hospital, Tabriz, Iran, during 2013-2014. Data collection was performed by the head nurse and treating physician using a pre-designed questionnaire. Most of the data were extracted from the neonatal records. Information regarding maternal underlying diseases and health care during pregnancy was extracted from mothers' records.Results: A total of 891 neonates were admitted to NICU of Taleghani Hospital of Tabriz, Iran, during 2013-2014, 68 (7.5% of whom died. Among these cases, 37 (%54.4 were male, 29 (29.4% were extremely low birth weight, and 16 (23.5% weighed more than 2.5 kg. The main causes of mortality were congenital anomalies (35.3%, prematurity (26.5%, and sepsis (10.3%, respectively.Conclusion: Congenital anomaly is the most common cause of mortality, and the pattern of death is changing from preventable diseases to unavoidable mortalities
Healy, Patricia; Fallon, Anne
This article reviews the origins and evolution of neonatology and considers the role of the neonatal nurse within this specialty. Neonatal nurses are a vital part of the neonatal team that provides care for sick babies. The nursing care required by sick babies and their families on a neonatal unit can be variable and complex. The past century has seen significant changes in the role of the neonatal nurse. This has come about through dramatic technological developments on neonatal units, an increased understanding of neonatal physiology and pathology, changes in the education of neonatal nurses, and active and ongoing clinical research within the specialty. The resulting significant advances in neonatal care, including that provided by neonatal nurses, have made a crucial and steadfast contribution to marked improvements in neonatal outcomes.
Komatsu, Midori; Tanaka, Makoto; Morimatsu, Mitsunori; Hirai, Shunsaku; Heshiki, Atsuko
We investigated whether CT had any advantage over pneumomediastinography (PMG) for the visualization of thymus in twenty-one patients with myasthenia gravis (MG). In two cases of thymoma which had been suspected with chest radiography, CT demonstrated an anterior mediastinal tumor distinguishable from other mediastinal organs, and for these cases PMG was not performed. Excluding three patients who were submitted to PMG only, CT of the anterior mediastinum was carried out in sixteen patients of MG, revealing thymic shadows in seven (44%). PMG followed by conventional tomography was done subsequently in three of these seven cases, for whom thymectomy was indicated because of uncontrollable myasthenic symptoms, and in all patients finger-like thymic shadows were disclosed. The vertical extension of thymus was more easily demonstrable by PMG than CT. PMG was carried out in six of nine patients in whom CT was negative, and in all cases thymic shadows were obvious with subsequent conventional tomography. Consequently, false negative rate of CT was at least 38% (6/16) with regard to the visualization of the nontumorous thymus. Although CT of the anterior mediastinum is useful as a screening method because of its non-invasiveness, its negative result does not rule out an absence of the pathologic thymus in view of its high false negative rate. In this regard, PMG is still necessary for the final determination of the thymic configuration in the MG patients. (J.P.N.)
Full Text Available Abayneh Girma Demisse, Fentahun Alemu, Mahlet Abayneh Gizaw, Zemene Tigabu School of Medicine, College of Medicine and Health Science, University of Gondar, Gondar, Ethiopia Introduction: The neonatal period is a highly vulnerable time for an infant completing many of the physiologic adjustments required for life outside the uterus. As a result, there are high rates of morbidity and mortality. The three major causes of mortality in developing countries include prematurity, infection, and perinatal asphyxia. The aim of this study was to identify the patterns of neonatal admission and factors associated with mortality among neonates admitted at the Neonatal Intensive Care Unit (NICU of University of Gondar Hospital.Materials and methods: A retrospective cross-sectional study was conducted among all admitted neonates in the NICU of University of Gondar referral hospital from December 1, 2015 to August 31, 2016. Information was extracted retrospectively during admission from patient records and death certificates, using a pretested questionnaire. The data were entered and analyzed using SPSS version 20, and p-values <0.05 were considered statistically significant.Results: A total of 769 neonates was included in the study. There were 448 (58.3% male neonates, and 398 (51.8% neonates were rural residents. More than two-thirds of the 587 deliveries (76.3% were performed in tertiary hospitals. Neonatal morbidity included hypothermia 546 (71%, sepsis 522 (67.9%, prematurity 250 (34.9%, polycythemia 242 (31.5%, hypoglycemia 142 (18.5, meconium aspiration syndrome 113 (14.7%, and perinatal asphyxia 96 (12.5%. The overall mortality was 110 (14.3%; 95% confidence interval [CI]: 11.9–16.9 of which 69 (62.7% deaths occurred in the first 24 hours of age. In the multivariate analysis, mortality was associated with perinatal asphyxia (adjusted odds ratio [AOR]: 5.97; 95% CI: 3.06–11.64, instrumental delivery (AOR: 2.99; 95% CI: 1.08–8.31, and early onset
Fischer, Hendrik S.
As yet, little is known about the effects of air leakages during CPAP in newborns. The present doctoral dissertation investigates tidal volume and leak measurements during nasal continuous positive airway pressure in neonates using a commercial ventilatory device. Investigations include in vitro studies, modelling and computer simulation as well as a clinical randomized cross-over trial in neonates.
Weiss, Alison R; Nadji, Ryhan; Bachevalier, Jocelyne
The lateral prefrontal cortex is known for its contribution to working memory (WM) processes in both humans and animals. Yet, recent studies indicate that the prefrontal cortex is part of a broader network of interconnected brain areas involved in WM. Within the medial temporal lobe (MTL) structures, the perirhinal cortex, which has extensive direct interactions with the lateral and orbital prefrontal cortex, is required to form active/flexible representations of familiar objects. However, its participation in WM processes has not be fully explored. The goal of this study was to assess the effects of neonatal perirhinal lesions on maintenance and monitoring WM processes. As adults, animals with neonatal perirhinal lesions and their matched controls were tested in three object-based (non-spatial) WM tasks that tapped different WM processing domains, e.g., maintenance only (Session-unique Delayed-nonmatching-to Sample, SU-DNMS), and maintenance and monitoring (Object-Self-Order, OBJ-SO; Serial Order Memory Task, SOMT). Neonatal perirhinal lesions transiently impaired the acquisition of SU-DNMS at a short (5 s) delay, but not when re-tested with a longer delay (30 s). The same neonatal lesions severely impacted acquisition of OBJ-SO task, and the impairment was characterized by a sharp increase in perseverative errors. By contrast, neonatal perirhinal lesion spared the ability to monitor the temporal order of items in WM as measured by the SOMT. Contrary to the SU-DNMS and OBJ-SO, which re-use the same stimuli across trials and thus produce proactive interference, the SOMT uses novel objects on each trial and is devoid of interference. Therefore, the impairment of monkeys with neonatal perirhinal lesions on SU-DNMS and OBJ-SO tasks is likely to be caused by an inability to solve working memory tasks with high proactive interference. The sparing of performance on the SOMT demonstrates that neonatal perirhinal lesions do not alter working memory processes per se but
Alison R Weiss
Full Text Available The lateral prefrontal cortex is known for its contribution to working memory (WM processes in both humans and animals. Yet, recent studies indicate that the prefrontal cortex is part of a broader network of interconnected brain areas involved in WM. Within the medial temporal lobe structures, the perirhinal cortex, which has extensive direct interactions with the lateral and orbital prefrontal cortex, is required to form active/flexible representations of familiar objects. However, its participation in WM processes has not be fully explored. The goal of this study was to assess the effects of neonatal perirhinal lesions on maintenance and monitoring WM processes. As adults, animals with neonatal perirhinal lesions and their matched controls were tested in three object-based (non-spatial WM tasks that tapped different WM processing domains, e.g. maintenance only (Session-unique Delayed-nonmatching-to Sample, SU-DNMS, and maintenance and monitoring (Object-Self-Order, OBJ-SO; Serial Order Memory Task, SOMT. Neonatal perirhinal lesions transiently impaired the acquisition of SU-DNMS at a short (5s delay, but not when re-tested with a longer delay (30s. The same neonatal lesions severely impacted acquisition of OBJ-SO task, and the impairment was characterized by a sharp increase in perseverative errors. By contrast, neonatal perirhinal lesion spared the ability to monitor the temporal order of items in WM as measured by the SOMT. Contrary to the SU-DNMS and OBJ-SO, which re-use the same stimuli across trials and thus produce proactive interference, the SOMT uses novel objects on each trial and is devoid of interference. Therefore, the impairment of monkeys with neonatal perirhinal lesions on SU-DNMS and OBJ-SO tasks is likely to be caused by an inability to solve working memory tasks with high proactive interference. The sparing of performance on the SOMT demonstrates that neonatal perirhinal lesions do not alter working memory processes per se
Holm, Kristina Garne; Brødsgaard, Anne; Zachariassen, Gitte
participatory design and qualitative methods. Data were collected from observational studies, individual interviews, and focus group interviews. Two neonatal units participated. One unit was experienced in providing neonatal home care with home visits, and the other planned to offer neonatal home care......BACKGROUND: For the majority of preterm infants, the last weeks of hospital admission mainly concerns tube feeding and establishment of breastfeeding. Neonatal home care (NH) was developed to allow infants to remain at home for tube feeding and establishment of breastfeeding with regular home...... visits from neonatal nurses. For hospitals covering large regions, home visits may be challenging, time consuming, and expensive and alternative approaches must be explored. OBJECTIVE: To identify parental needs when wanting to provide neonatal home care supported by telemedicine. METHODS: The study used...
Rath, Chandra; Suryawanshi, Pradeep
Knowledge and skills of heart, head, lung, gut and basic abdominal ultrasound is of immense utility to clinicians in their day-to-day patient management, and in acute events, in the absence of specialist service back-up. This review examines the potential role of clinician-performed ultrasound in the neonatal intensive care unit. The bibliographic search of English-language literature was performed electronically using PubMed and EMBASE databases for the different topics we have covered under this review. Bedside head ultrasound can be used to identify and screen for intraventricular hemorrhage, periventricular leukomalacia and post-hemorrhagic ventricular dilatation. It is also a useful adjuvant tool in the evaluation of hypoxic ischemic encephalopathy. The relatively new lung ultrasound technique is useful in identifying transient tachypnea, pneumonia, pneumothorax, fluid overload and pleural effusion. Gut ultrasound is useful in identifying necrotizing enterocolitis and probably is better than X-ray in prognostication. Ultrasound is also useful in identifying vascular line positions without radiation exposure. Ultrasound performed by the clinician has an extensive role in the neonatal intensive care unit. Basic ultrasound knowledge of head, lung and gut is a useful supplement to clinical decision-making.
Palma, Jonathan P.; Benitz, William E.; Tarczy-Hornoch, Peter; Butte, Atul J.; Longhurst, Christopher A.
The future of neonatal informatics will be driven by the availability of increasingly vast amounts of clinical and genetic data. The field of translational bioinformatics is concerned with linking and learning from these data and applying new findings to clinical care to transform the data into proactive, predictive, preventive, and participatory health. As a result of advances in translational informatics, the care of neonates will become more data driven, evidence based, and personalized. PMID:22924023
Hirose, Genjiro; Yamamoto, Teiji; Kosoegawa, Hiroshi; Saeki, Mitsuo; Hayashi, Toshiharu
Nine patients with myasthenia gravis (MG) had plain chest X-ray, tomography, computed tomography (CT) of the thorax, pneumomediastinography (PMG) and post-PMG CT scans. Routine chest radiography detected mediastinal masses in two patients and conventional laminogram provided no additional informations. CT yielded anterior mediastinal increased densities in seven patients (78%), whereas post-PMG CT delineated masses (thymoma or thymic hyperplasia) or thymic gland in all cases (100%), but these procedures could not distinguish thymic tumor from nontumorous conditions. PMG and post-PMG CT scans are superior to other radiographic techniques in detecting mediastinal abnormalities with more clear delineation of thymoma or thymic gland. When an abnormal density is present in the mediastinum of a patient with MG, PMG and post-PMG CT scans should be done to outline the mediastinal anatomy, to determine the size, extent, invasiveness of thymoma or thymic gland prior to thymectomy. (author)
Hirose, Genjiro; Yamamoto, Teiji; Kosoegawa, Hiroshi; Saeki, Mitsuo; Hayashi, Toshiharu (Kanazawa Medical Univ., Ishikawa (Japan))
Nine patients with myasthenia gravis (MG) had plain chest X-ray, tomography, computed tomography (CT) of the thorax, pneumomediastinography (PMG) and post-PMG CT scans. Routine chest radiography detected mediastinal masses in two patients and conventional laminogram provided no additional information. CT yielded anterior mediastinal increased densities in seven patients (78%), whereas post-PMG CT delineated masses (thymoma or thymic hyperplasia) or thymic gland in all cases (100%), but these procedures could not distinguish thymic tumor from nontumorous conditions. PMG and post-PMG CT scans are superior to other radiographic techniques in detecting mediastinal abnormalities with more clear delineation of thymoma or thymic gland. When an abnormal density is present in the mediastinum of a patient with MG, PMG and post-PMG CT scans should be done to outline the mediastinal anatomy, to determine the size, extent, invasiveness of thymoma or thymic gland prior to thymectomy.
Full Text Available To determine whether there is a significant association between maternal haemoglobin measured before delivery and short-term neonatal outcome in very preterm neonates.We included prospectively all live births occurring from 25 to 32+6 weeks of gestation in a tertiary care centre between January 1(st 2009 and December 31(st 2011. Outborn infants and infants presenting with lethal malformations were excluded. Three hundred and thirty-nine mothers and 409 infants met the inclusion criteria. For each mother-infant pair a prospective record of epidemiologic data was performed and maternal haemoglobin concentration recorded within 24 hours before delivery was retrospectively researched. Maternal haemoglobin was divided into quartiles with the second and the third one regarded as reference as they were composed of normal haemoglobin values. Short-term outcome was defined as poor in case of death during hospital stay and/or grades III/IV intraventricular haemorrhage and/or periventricular leukomalacia and/or necessity of ventriculoperitoneal shunt.The global rate of poor short-term neonatal outcome was 11.4% and was significantly associated with low maternal haemoglobin values. This association remained significant after adjustment for antenatal corticosteroids therapy, gestational age, parity, mechanism of preterm birth, mode of delivery and birth weight (aOR = 2.97 CI 95% [1.36-6.47]. There was no relation between short-term neonatal outcome and high maternal haemoglobin concentration values.We show that low maternal haemoglobin concentration at delivery is an independent risk factor for poor short-term neonatal outcome in very preterm neonates. This study is one of the first to show such an association within the preterm population.
Drugs are very strong tools used to improve outcome in neonates. Despite this fact and in contrast to tailored perfusion equipment, incubators or ventilators for neonates, we still commonly use drug formulations initially developed for adults. We would like to make the point that drug formulations given to neonates need to be tailored for this age group. Besides the obvious need to search for active compounds that take the pathophysiology of the newborn into account, this includes the dosage and formulation. The dosage or concentration should facilitate the administration of low amounts and be flexible since clearance is lower in neonates with additional extensive between-individual variability. Formulations need to be tailored for dosage variability in the low ranges and also to the clinical characteristics of neonates. A specific focus of interest during neonatal drug development therefore is a need to quantify and limit excipient exposure based on the available knowledge of their safety or toxicity. Until such tailored vials and formulations become available, compounding practices for drug formulations in neonates should be evaluated to guarantee the correct dosing, product stability and safety.
Kassab, Manal; Khriesat, Wadah M; Anabrees, Jasim
Transient tachypnoea of the newborn (TTN) results from delayed clearance of lung liquid and is a common cause of admission of full-term infants to neonatal intensive care units. The condition is particularly common after elective caesarean section. Conventional treatment involves appropriate oxygen administration and continuous positive airway pressure in some cases. Most infants receive antibiotic therapy. Hastening the clearance of lung liquid may shorten the duration of the symptoms and reduce complications. To determine whether diuretic administration reduces the duration of oxygen therapy and respiratory symptoms and shortens hospital stay in term infants presenting with transient tachypnoea of the newborn. An updated search was carried out in September 2015 of the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 9, 2015), MEDLINE via Ovid, EMBASE, PubMed, and CINAHL via OVID. We included randomised and quasi-randomised controlled trials that compared the effect of diuretics administration versus placebo or no treatment in infants of less than seven days of age, born at 37 or more weeks of gestation with the clinical picture of transient tachypnoea of the newborn. We extracted and analysed data according to the methods outlined in the latest Cochrane Handbook for Systematic Reviews of Interventions. Two review authors assessed trial quality in each potentially eligible manuscript and two review authors extracted data. Our previous systematic review included two trials enrolling a total of 100 infants with transient tachypnoea of the newborn (Wiswell 1985; Karabayir 2006). The updated search revealed no new trials. Wiswell 1985 randomised 50 infants to receive either oral furosemide (2 mg/kg body weight at time of diagnosis followed by a 1 mg/kg dose 12 hours later if the tachypnoea persisted) or placebo. Karabayir 2006 randomised 50 infants to receive either intravenous furosemide (2 mg/kg body
Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study.
Howard, James F; Utsugisawa, Kimiaki; Benatar, Michael; Murai, Hiroyuki; Barohn, Richard J; Illa, Isabel; Jacob, Saiju; Vissing, John; Burns, Ted M; Kissel, John T; Muppidi, Srikanth; Nowak, Richard J; O'Brien, Fanny; Wang, Jing-Jing; Mantegazza, Renato
Complement is likely to have a role in refractory generalised myasthenia gravis, but no approved therapies specifically target this system. Results from a phase 2 study suggested that eculizumab, a terminal complement inhibitor, produced clinically meaningful improvements in patients with anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis. We further assessed the efficacy and safety of eculizumab in this patient population in a phase 3 trial. We did a phase 3, randomised, double-blind, placebo-controlled, multicentre study (REGAIN) in 76 hospitals and specialised clinics in 17 countries across North America, Latin America, Europe, and Asia. Eligible patients were aged at least 18 years, with a Myasthenia Gravis-Activities of Daily Living (MG-ADL) score of 6 or more, Myasthenia Gravis Foundation of America (MGFA) class II-IV disease, vaccination against Neisseria meningitides, and previous treatment with at least two immunosuppressive therapies or one immunosuppressive therapy and chronic intravenous immunoglobulin or plasma exchange for 12 months without symptom control. Patients with a history of thymoma or thymic neoplasms, thymectomy within 12 months before screening, or use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomisation, or rituximab within 6 months before screening, were excluded. We randomly assigned participants (1:1) to either intravenous eculizumab or intravenous matched placebo for 26 weeks. Dosing for eculizumab was 900 mg on day 1 and at weeks 1, 2, and 3; 1200 mg at week 4; and 1200 mg given every second week thereafter as maintenance dosing. Randomisation was done centrally with an interactive voice or web-response system with patients stratified to one of four groups based on MGFA disease classification. Where possible, patients were maintained on existing myasthenia gravis therapies and rescue medication was allowed at the study physician's discretion. Patients, investigators
Crawford, Doreen; Morris, Maryke
"Neonatal Nursing" offers a systematic approach to the nursing care of the sick newborn baby. Nursing actions and responsibilities are the focus of the text with relevant research findings, clinical applications, anatomy, physiology and pathology provided where necessary. This comprehensive text covers all areas of neonatal nursing including ethics, continuing care in the community, intranatal care, statistics and pharmokinetics so that holistic care of the infant is described. This book shou...
Full Text Available Background Rhesus incompatibility is a preventable cause for severe neonatal hyperbilirubinemia, hydrops fetalis and still births. The prevalence of the Rh-negative blood group among Indian woman varies from 2% - 10%. Despite declining the incidence of Rhesus incompatibility, due to availability of anti-D immunoglobulin, and improved antenatal care of the Rh-negative pregnant woman, it still accounts for a significant proportion of neonatal hyperbilirubinemia and neuro-morbidity. The prevalence of Rh-negative women having Rh-positive neonates is 60%. Objectives This study aimed to estimate the incidence of Rh iso-immunization and evaluate the outcomes of Rh iso-immunized neonates. Methods This prospective observational study was conducted in a tertiary level neonatal intensive care unit, Princess Esra hospital, Deccan college of medical sciences, Hyderabad, Telangana, India. Consecutive intramural and extramural neonates admitted to neonatal intensive care unit with the Rh-negative mother’s blood group and hyperbilirubinemia were enrolled. Neonates born to Rh+ve mothers were excluded. Neonatal gestational age, birth weight, age at admission, duration of phototherapy, duration of hospitalization, neonatal examination and investigations were recorded in a predesigned, pretested performa. Results A total of 90 neonates were born to Rh-negative mothers, of which 70% (63 had the Rh-positive blood group and 30% had the Rh-negative blood group. Of these 63 neonates, 48 (76.2% had hyperbilirubinemia and 43 neonates (68.3% had significant hyperbilirubinemia (total serum bilirubin > 15mg/dL. Among them, 2%, 75% and 23% were born to primi, multi and grandmutli, respectively. Also, 14.5% of the neonates were large for dates (LFD, 75% appropriate for dates (AFD and 10.5% were small for dates (SFD. Premature and SFD neonates had higher incidence of hyperbilirubinemia. Significantly higher incidence of jaundice occurred within 72 hours of life. The mean
Full Text Available BACKGROUND : Neonates receiving phototherapy have side effects like hypocalcemia and electrolyte changes. Our study is hereby intended to study the serum sodium changes due to phototherapy. AIMS : To evaluate the serum sodium changes in neonates receiving phototherapy f or neonatal hyperbilirubinemia. SETTINGS AND DESIGN : A prospective hospital based comparative study conducted on neonates admitted in the Neonatal Intensive Care Unit receiving phototherapy. METHODS AND MATERIAL : A predesigned proforma has aided the enroll ment of 252 newborns into the study. Serum bilirubin and serum sodium were determined before and after termination of phototherapy. The first samples were considered as controls. A comparative study was made between before and after phototherapy groups to determine the incidence of serum sodium imbalances. STATISTICAL ANALYSIS USED : Proportions will be compared using chi - square test. All data of various groups will be tabulated and statistically analyzed using suitable statistical tests (Student's t test. RESULTS : Male to Female ratio was 1.45 : 1. Incidence of low birth weight babies was 23% and preterm was 20.2%. Mean birth weight and gestational age was 2.84±0.51 kg and 38.44±1.98 wks respectively. Mean duration of phototherapy was 37.65±11.06 hrs. The incidence of hyponatremia post phototherapy found to be 6% which was more in low birth weight (LBW babies (17.2% , p48 hrs (p<0.001. Even the decline in mean serum sodium values after phototherapy found to be statistically significant. CONCLUSION : Our study shows that neonates u nder phototherapy are at higher risk of hyponatremia. This risk is greater in premature and LBW babies and hence this group of babies should be closely monitored for changes in serum sodium and should be managed accordingly.
Morris, Matthew C; Surendran, Naveen
While vaccines have been tremendously successful in reducing the incidence of serious infectious diseases, newborns remain particularly vulnerable in the first few months of their life to life-threatening infections. A number of challenges exist to neonatal vaccination. However, recent advances in the understanding of neonatal immunology offer insights to overcome many of those challenges. This review will present an overview of the features of neonatal immunity which make vaccination difficult, survey the mechanisms of action of available vaccine adjuvants with respect to the unique features of neonatal immunity, and propose a possible mechanism contributing to the inability of neonates to generate protective immune responses to vaccines. We surveyed recent published findings on the challenges to neonatal vaccination and possible intervention strategies including the use of novel vaccine adjuvants to develop efficacious neonatal vaccines. Challenges in the vaccination of neonates include interference from maternal antibody and excessive skewing towards Th2 immunity, which can be counteracted by the use of proper adjuvants. Synergistic stimulation of multiple Toll-like receptors by incorporating well-defined agonist-adjuvant combinations to vaccines is a promising strategy to ensure a protective vaccine response in neonates. © 2016 S. Karger AG, Basel.
Full Text Available Introduction: Congenital hypothyroidism is one of the most preventable causes of mental retardation. Worldwide, incidences vary from 1:3000 to 1:4000 and mean incidence in Iran is estimated to be 1:1000. Neonatal screening and early treatment within first 2 weeks of neonatal period can prevent neurocognitive deficits. We aimed to study the incidence of CH and increased levels of TSH in Yazd province and collect data describing the disease status and designing first and second levels of preventive interventions. Methods: This descriptive analytic study was performed by census cross sectional method on 13022 neonates in Yazd province in 2006-2007(March 2006- March 2007 including 6495 females and 6527 males. Sampling was done (within the first 3-5 days of life by lancet sticking of neonatal heel. After transfer of 3 blood drops over filter papers, the TSH level was measured. If the TSH level was equal or higher than 5 mu/l, additional confirmation tests were done. Neonates were diagnosed according to serum confirmation test (TSH10 mu/l or T4<6.5g/dl and underwent treatment according to national guidelines. Data was analyzed by SPSS software. Results: Total number of patients was 45, including 25 males (55.5% and 20 females (44.5%. Prevalence in males, females and overall was consecutively, 1:261, 1:325 and 1:289, but this difference was not statistically significant. Prevalence in urban and rural areas was 1:315 and 1:216, but the difference was statistically not significant. The prevalence during spring, summer, autumn& winter was 1:95, 1:250, 1:1934 and 1:369, respectively, that was statistically significant. Mean age at sampling was 7.2 days, mean TSH level 2.3 mu/l and mean age of mothers was 25.8 years. Conclusions: Incidence of CH and transient increased levels of TSH in Yazd province is significantly higher than national and worldwide levels that necessitate the constancy and reinforcement of neonatal screening program. On the other
JOSÉ LAMARTINE DE ASSIS
Full Text Available We evaluated the epidemiological, clinical, laboratory and therapeutical aspects of 41 patients with thymomatous myasthenia gravis. Thirty five patients (85.36% were submitted to thymectomy. Follow-up ranged from two to 18 years. Diagnosis of thymoma was based upon clinical investigations and CT scan of the anterior mediastinum and in 11 patients supported by immunological tests of anti-striated muscle antibodies with a positive result in more than 80% of cases. Histopathologic examination of all thymomectomized patients confirmed the diagnosis of thymoma. There was a significant predominance of benign over malignant thymoma. Occurred higher prevalence of male patients and of patients over 40 years of age. The therapeutical strategy to control myasthenic clinical findings was the same as that for non-thymomatous myasthenia gravis. The corticosteroids associated to cytotoxic drugs were less often used. Radiotherapy of the anterior mediastinum was more often used in patients having invasive tumors submitted to surgery or not. With regard to survival and control of myasthenia gravis, especially in younger patients and in those submitted to early surgery, results of treatment were surprisingly favorable.Avaliamos 41 pacientes com miastenia grave timomatosa sob os aspectos epidemiológico, clínico e terapêutico. Trinta e cinco pacientes (85,36% foram timectomizados. O seguimento clínico variou de dois meses até 18 anos. O diagnóstico do timoma foi fundamentado no estudo de imagem do mediastino (tomografia axial computadorizada e, em 11 pacientes, complementado com a determinação sérica de anticorpos para músculo estriado com resultado positivo em mais de 80% dos casos e confirmado pelo exame anátomo-patológico do timo realizado em todos os pacientes operados. Ocorreu predomínio significante de timomas benignos sobre timomas malignos, forma clínica generalizada severa, frequente envolvimento do sexo masculino e, em pacientes com mais de
Oshima, Minako; Iida-Klein, Akiko; Maruta, Takahiro; Deitiker, Philip R; Atassi, M Zouhair
Experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis (MG), can be induced in C57BL/6 (B6, H-2 b ) mice by 2-3 injections with Torpedo californica AChR (tAChR) in complete Freund's adjuvant. Some EAMG mice exhibit weight loss with muscle weakness. The loss in body weight, which is closely associated with bone structure, is particularly evident in EAMG mice with severe muscle weakness. However, the relationship between muscle weakness and bone loss in EAMG has not been studied before. Recent investigations on bone have shed light on association of bone health and immunological states. It is possible that muscle weakness in EAMG developed by anti-tAChR immune responses might accompany bone loss. We determined whether reduced muscle strength associates with decreased bone mineral density (BMD) in EAMG mice. EAMG was induced by two injections at 4-week interval of tAChR and adjuvants in two different age groups. The first tAChR injection was either at age 8 weeks or at 15 weeks. We measured BMD at three skeletal sites, including femur, tibia, and lumbar vertebrae, using dual energy X-ray absorptiometry. Among these bone areas, femur of EAMG mice in both age groups showed a significant decrease in BMD compared to control adjuvant-injected and to non-immunized mice. Reduction in BMD in induced EAMG at a later-age appears to parallel the severity of the disease. The results indicate that anti-tAChR autoimmune response alone can reduce bone density in EAMG mice. BMD reduction was also observed in adjuvant-injected mice in comparison to normal un-injected mice, suggesting that BMD decrease can occur even when muscle activity is normal. Decreased BMD observed in both tAChR-injected and adjuvant-injected mice groups were discussed in relation to innate immunity and bone-related immunology involving activated T cells and tumour necrosis factor-related cytokines that trigger osteoclastogenesis and bone loss.
Wang, Cong-Cong; Zhang, Min; Li, Heng; Li, Xiao-Li; Yue, Long-Tao; Zhang, Peng; Liu, Ru-Tao; Chen, Hui; Li, Yan-Bin; Duan, Rui-Sheng
We have previously demonstrated that Cysteinyl aspartate-specific proteinase-1 (caspase-1) inhibitor ameliorates experimental autoimmune myasthenia gravis (EAMG) by inhibited cellular immune response, via suppressing DC IL-1 β, CD4 + T and γdT cells IL-17 pathways. In this study, we investigated the effect of caspase-1 inhibitor on humoral immune response of EAMG and further explore the underlying mechanisms. An animal model of MG was induced by region 97-116 of the rat AChR α subunit (R97-116 peptide) in Lewis rats. Rats were treated with caspase-1 inhibitor Ac-YVAD-cmk intraperitoneally (i.p.) every second day from day 13 after the first immunization. Flow cytometry, western blot, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the neuroprotective effect of caspase-1 inhibitor on humoral immune response of EAMG. The results showed that caspase-1 inhibitor reduced the relative affinity of anti-R97-116 IgG, suppressed germinal center response, decreased follicular helper T cells, and increased follicular regulatory T cells and regulatory B cells. In addition, we found that caspase-1 inhibitor inhibited humoral immunity response in EAMG rats via suppressing IL-6-STAT3-Bcl-6 pathways. These results suggest that caspase-1 inhibitor ameliorates EAMG by regulating humoral immune response, thus providing new insights into the development of myasthenia gravis and other autoimmune diseases therapies. Copyright © 2017 Elsevier B.V. All rights reserved.
Maria Vera Lúcia Moreira Leitão Cardoso
Full Text Available The aim of this study was to characterize the treatments applied to newborns with congenital malformation hospitalized in a neonatal unit and to identify whether there is an association among the treatments used and the type of malformation. A descriptive, prospective and quantitative study was developed in a public institution in Fortaleza, Ceará, Brazil. Data were collected using the medical records of 30 neonates with congenital malformations. The incidence of malformations was higher among females, regardless of the mother’s age, gestational age or weight at birth; malformations of the central nervous and musculoskeletal systems prevailed. The treatments used varied according to the clinical evolution of the neonate. The data collected did not present statistical significance when associated with the variable of congenital malformation and the treatments used (p>0.05. The treatments are not directly related to the type of malformation, but to the clinical condition of the neonate.
Differences from adults and children in physiology and anatomy of neonates inform our ... is based on energy expenditure indexed to bodyweight.2 Energy ... fragile and poorly keratinised.5 ... neonates means that very conservative fluid regimes in neonates ..... I make an estimation of insensible loss from the skin, viscera,.
Jaruratanasirikul, Somchit; Piriyaphan, Jutarat; Saengkaew, Tansit; Janjindamai, Waricha; Sriplung, Hutcha
Congenital hypothyroidism (CH) is one of the common causes of intellectual disability which can be prevented by early detection of an elevated thyroid stimulating hormone (TSH) level in the newborn and by treatment with thyroxine. In Thailand, neonatal TSH screening was implemented nationwide in 2005. The objective of the study was to determine the etiologies and the estimated incidences of CH in southern Thailand before and after the implementation of a neonatal TSH screening program in 2005. The medical records of pediatric patients who were diagnosed with primary CH at Songklanagarind Hospital during 1995-2013 were retrospectively reviewed. The study was divided into two time periods: study period 1 (SP1) (1995-2004) and study period 2 (SP2) (2005-2013), the time before and after TSH program implementation. The most common form of CH during SP1 was overt permanent CH (66%), mostly caused by athyreosis or ectopic thyroid. In SP2, the most common form of CH was mild permanent CH (39%) (mostly due to dyshormonogenesis), followed by overt CH (32%) and transient CH (29%). The overall annual estimated incidence of CH per 10,000 live births in Songkhla Province was 1.69 (1:5021) in SP1, increasing to 4.77 (1:2238) in SP2; in all 14 provinces in southern Thailand, the estimated incidence was 1.24 (1:8094) in SP1 and 2.33 (1:4274) in SP2. Neonatal TSH screening has a significant impact on the increased detection of the mild form of permanent and transient CH cases, which may be important for the prevention of brain damage from less severe CH although this remains to be documented.
Zwanenburg, Alex; Andriessen, Peter; Jellema, Reint K; Niemarkt, Hendrik J; Wolfs, Tim G A M; Kramer, Boris W; Delhaas, Tammo
Seizures below one minute in duration are difficult to assess correctly using seizure detection algorithms. We aimed to improve neonatal detection algorithm performance for short seizures through the use of trend templates for seizure onset and end. Bipolar EEG were recorded within a transiently asphyxiated ovine model at 0.7 gestational age, a common experimental model for studying brain development in humans of 30-34 weeks of gestation. Transient asphyxia led to electrographic seizures within 6-8 h. A total of 3159 seizures, 2386 shorter than one minute, were annotated in 1976 h-long EEG recordings from 17 foetal lambs. To capture EEG characteristics, five features, sensitive to seizures, were calculated and used to derive trend information. Feature values and trend information were used as input for support vector machine classification and subsequently post-processed. Performance metrics, calculated after post-processing, were compared between analyses with and without employing trend information. Detector performance was assessed after five-fold cross-validation conducted ten times with random splits. The use of trend templates for seizure onset and end in a neonatal seizure detection algorithm significantly improves the correct detection of short seizures using two-channel EEG recordings from 54.3% (52.6-56.1) to 59.5% (58.5-59.9) at FDR 2.0 (median (range); p seizures by EEG monitoring at the NICU.
Werneck, L C; Bittencourt, P C; Nóvak, E M
It is reported a case of a 61 years-old man with progressive asthenia, disfagia, disphonia and diplopia, of variable intensity during the day, who had a very good response to anticolinesterasic drugs and corticosteroids. The repetitive stimulation tests at low frequency, resulted in large increment (maximum 275%) of the basal voltage after exercise. At high frequency he also had a large increment. Radiological and laboratory investigation three times in a seven-year period was normal, without evidence of any neoplasia. Muscle biopsy showed a type II muscle fiber atrophy. The repetitive stimulation tests repeated three times, was typical of myasthenia gravis in one occasion and in the other two, typical of myasthenic syndrome (increment of 418%). A discussion about other cases with similar findings is made after a review of the literature.
Lorenzoni, Paulo José; Ducci, Renata Dal-Prá; Tensini, Tallulah Spina; Dalledone, Giuliano; Kay, Claudia Suemi Kamoi; de Paola, Luciano; Werneck, Lineu Cesar; Scola, Rosana Herminia; Silvado, Carlos
The relationship between myasthenia gravis (MG) and epilepsy has been rarely reported. As consequence, there are no specific guidelines for the management of these conditions when they mutually occur. We reported on three patients in whom epilepsy and MG are coexisting, but in different clinical settings. Two patients were treated with antiepileptic drugs which improved their symptoms. One patient has controlled the seizures after a successful anterior temporal lobectomy with no appreciable consequences to her MG. We discuss the difficulties in the management of epilepsy in patients with MG. In addition, we report on the first epileptic surgery in a MG patient, indicating that this surgical procedure as a safe option for the treatment of intractable epilepsy in patients with MG. Copyright © 2017. Published by Elsevier Ltd.
Full Text Available Prikazali smo slučaj 22-godišnjeg muskarca sa kliničkom slikom otežanog gutanja i dvoslika. Bolest myasthenia gravis (MG je dijagnostikovana na osnovu pozitivnog faramakološkog testa, pozitivnog testa neuromišićne transmisije, kompjuterizovane tomografije medijastinuma. Antitela protiv acetilholinskog receptora (AChR i antitela protiv mišićno specifičnog receptora za tirozin kinazu (MuSK. bila su negativna. Zabeleženo je delimično poboljšanje u neurološkom nalazu na ordiniranu terapiju Piridostigminom, Ciklosporinom, kortikosteroidima. Bolesnik je imao povoljan odgovor na izmenu plazme sa povlačenjem svih kliničkih siimptoma što potvrdjuje hipotezu o učešću humoralnih faktora u patogenezi dvostruko negativne MG.
Holm, Kristina Garne
Neonatal homecare (NH) implies that parents manage tube feeding and care of their preterm infant at home supported by home visits from neonatal nurses, to monitor infant growth and the well-being of the family. Home visits are costly and time consuming in rural areas. The overall aim of this study...
A Arturo eLeis
Full Text Available Eye trauma and blindness are common in the United States, with an incidence of over 2 million cases per year and 25 million blind adults, respectively. However, literature is surprisingly scarce on the potential confounding effect of eye trauma or blindness on the diagnosis of myasthenia gravis (MG, an autoimmune neuromuscular disease in which fluctuating ocular symptoms are the most distinguishing feature. We present the case of a 75 year-old man with eye enucleation referred for electrodiagnostic evaluation of the right upper limb after an accidental fall. Neurological examination showed proximal muscle weakness, but MG was not initially considered because the patient lacked the classic ocular symptoms of MG. The delay in diagnosis resulted in worsening of systemic MG symptoms, although in other patients it may have precipitated MG crisis or possibly death. Greater awareness that eye trauma or blindness can prevent expression of ocular symptoms in neuromuscular disorders is needed to avoid morbidity associated with an erroneous or delayed diagnosis.
Popperud, T H; Boldingh, M I; Rasmussen, M; Kerty, E
This study aimed to characterize juvenile myasthenia gravis in a national population-based cohort in Norway, and to evaluate long-term outcome and potential differences correlated with prepubertal versus postpubertal disease onset. Patients with onset of myasthenia gravis aged ≤18 years were identified through multiple strategies. Retrospective clinical data were collected by means of medical charts. All patients had an updated clinical examination. Cases were divided into prepubertal and postpubertal onset using age 12 years as the cut off. In total, 75 patients were identified of whom 63 were included in the study: 21 in the prepubertal and 42 in the postpubertal onset group. There was a female preponderance in both groups. In total, 59% presented with ocular symptoms, but the great majority of patients in both groups generalized during the two first years of the disease. Myasthenic crisis was more frequent in the prepubertal onset group. All patients were initially treated with pyridostigmine, 26 with steroids, and 17 with other immunosuppressive treatment. The postpubertal cases were more often treated with immunosuppressive therapy. Fifty patients (79%) underwent thymectomy. The general outcome was favourable: 57% became asymptomatic and only four subjects failed to attain clinical improvement. One-third had at least one additional autoimmune disease. Despite frequent symptom generalization and a subgroup of prepubertal onset with severe disease, the long-term outcome was good, especially in the thymectomized prepubertal onset group. Polyautoimmunity occurred in both groups in one-third. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.
Berbel Tornero, O; Ortega García, J A; Ferrís i Tortajada, J; García Castell, J; Donat i Colomer, J; Soldin, O P; Fuster Soler, J L
The association between pediatric cancer and congenital abnormalities is well known but, there is no exclusive data on the neonatal period and the underlying etiopathogenic mechanisms are unknown. First, to analyze the frequency of neonatal tumours associated with congenital abnormalities; and second, to comment on the likely etiopathogenic hypotheses of a relationship between neonatal tumours and congenital abnormalities. Historical series of neonatal tumours from La Fe University Children's Hospital in Valencia (Spain), from January 1990 to December 1999. Histological varieties of neonatal tumours and associated congenital abnormalities were described. A systematic review of the last 25 years was carried out using Medline, Cancerlit, Index Citation Science and Embase. The search profile used was the combination of "neonatal/congenital-tumors/cancer/neoplasms" and "congenital malformations/birth defects". 72 neonatal tumours were identified (2.8% of all pediatric cancers diagnosed in our hospital) and in 15 cases (20.8%) there was some associated malformation, disease or syndrome. The association between congenital abnormalities and neonatal tumours were: a) angiomas in three patients: two patients with congenital heart disease with a choanal stenosis, laryngomalacia; b) neuroblastomas in two patients: horseshoe kidney with vertebral anomalies and other with congenital heart disease; c) teratomas in two patients: one with cleft palate with vertebral anomalies and other with metatarsal varus; d) one tumour of the central nervous system with Bochdaleck hernia; e) heart tumours in four patients with tuberous sclerosis; f) acute leukaemia in one patient with Down syndrome and congenital heart disease; g) kidney tumour in one case with triventricular hydrocephaly, and h) adrenocortical tumour: hemihypertrophy. The publications included the tumours diagnosed in different pediatric periods and without unified criteria to classify the congenital abnormalities. Little data
Celebi, Miray Yilmaz; Alan, Serdar; Kahvecioglu, Dilek; Cakir, Ufuk; Yildiz, Duran; Erdeve, Omer; Arsan, Saadet; Atasay, Begum
This study aims to evaluate the effect of the prophylactic continuous positive airway pressure (CPAP) administration in the delivery room to newborns who were delivered by elective cesarean section (CS). Inborn infants with gestational age between 34(0/7) to 38(6/7) and born by elective CS were prospectively randomized to receive either prophylactic CPAP for 20 minutes via face mask or standardized care without CPAP in the delivery room. Primary outcomes were the incidence of transient tachypnea of the newborn (TTN) and neonatal intensive care unit (NICU) admission due to respiratory distress. A total of 259 infants with a mean gestational age of 37.7 ± 0.8 weeks and birth weight of 3,244 ± 477 g were included. A total of 134 infants received prophylactic CPAP and 125 received control standard care. The rate of NICU admission was significantly lower in prophylactic CPAP group (p = 0.045). Although the rate of TTN was lower in the prophylactic CPAP group, the difference was not statistically significant (p = 0.059). The rate of NICU admission due to respiratory distress was significantly higher in late-preterm cohort than early-term cohort (p CPAP administration decreases the rate of NICU admission without any side effect in late-preterm and early-term infants delivered by elective CS. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Woolley, F R; Schuman, K L; Lyon, J L
A cohort study of neonatal mortality (N = 106) in white singleton births (N = 14,486) in Utah for January-June 1975 was conducted. Using membership and activity in the Church of Jesus Christ of Latter-day Saints (LDS or Mormon) as a proxy for parental health practices, i.e., tobacco and alcohol abstinence, differential neonatal mortality rates were calculated. The influence of potential confounding factors was evaluated. Low activity LDS members were found to have an excess risk of neonatal death five times greater than high activity LDS, with an upper bound of a two-sided 95% confidence interval of 7.9. The data consistently indicate a lower neonatal mortality rate for active LDS members. Non-LDS were found to have a lower rate than either medium or low activity LDS.
Full Text Available Abstract Background Neonatal sepsis is a significant cause of morbidity and mortality in neonates. Appropriate clinical diagnosis and empirical treatment in a given setting is crucial as pathogens of bacterial sepsis and antibiotic sensitivity pattern can considerably vary in different settings. This study was conducted at Bugando Medical Centre (BMC, Tanzania to determine the prevalence of neonatal sepsis, predictors of positive blood culture, deaths and antimicrobial susceptibility, thus providing essential information to formulate a policy for management of neonatal sepsis. Methods This was a prospective cross sectional study involving 300 neonates admitted at BMC neonatal unit between March and November 2009. Standard data collection form was used to collect all demographic data and clinical characteristics of neonates. Blood culture was done on Brain Heart Infusion broth followed by identification of isolates using conventional methods and testing for their susceptibility to antimicrobial agents using the disc diffusion method. Results Among 770 neonates admitted during the study period; 300 (38.9% neonates were diagnosed to have neonatal sepsis by WHO criteria. Of 300 neonates with clinical neonatal sepsis 121(40% and 179(60% had early and late onset sepsis respectively. Positive blood culture was found in 57 (47.1% and 92 (51.4% among neonates with early and late onset neonatal sepsis respectively (p = 0.466. Predictors of positive blood culture in both early and late onset neonatal sepsis were inability to feed, lethargy, cyanosis, meconium stained liquor, premature rupture of the membrane and convulsion. About 49% of gram negatives isolates were resistant to third generation cephalosporins and 28% of Staphylococcus aureus were found to be Methicillin resistant Staphylococcus aureus (MRSA. Deaths occurred in 57 (19% of neonates. Factors that predicted deaths were positive blood culture (p = 0.0001, gram negative sepsis (p = 0.0001 and
Full Text Available The objective of the research is to study neonatal adaptation in new-born children from the tobacco abused mothers. A comparative analysis of clinical and neuroendochnal status and lipid metabolism in new-born children from smoking and non-smoking mothers was carried out Neonatal adaptation disorders were revealed in new-born children from the smoking mothers.
Desy Fitri Yani
Full Text Available Indonesia bersama seluruh negara berkembang berupaya mencapai kesepakatan Millenium Development Goals (MDGs dengan salah satu sasaran menurunkan angka kematian neonatal dari 20 per 1.000 kelahiran hidup menjadi 15 per 1.000 kelahiran hidup. Penelitian ini bertujuan mengetahui hubungan pelayanan kesehatan ibu dengan kematian neonatal di Kabupaten Lampung Timur tahun 2011. Penelitian dengan desain studi kasus kontrol ini mengamati kasus ibu yang mengalami kematian neonatal dan kontrol ibu yang tidak mengalami kematian neonatal. Analisis multivariat menemukan pelayanan antenatal dan pertolongan persalinan berhubungan secara signifikan dengan kematian neonatal, setelah mengendalikan variabel umur ibu dan riwayat kehamilan (OR = 16,32; nilai p = 0,000; dan (OR = 18,36; nilai p = 0,31. Bayi yang dilahirkan dari Ibu dengan pelayanan antenatal tidak lengkap berisiko mengalami kematian neonatal 16,32 dan 18,36 kali lebih besar daripada bayi yang dilahirkan. Ibu dengan pelayanan antenatal lengkap dan penolong persalinan profesional. Tidak ada hubungan penolong persalinan dengan kematian neonatal, setelah mengontrol variabel pelayanan antenatal, umur ibu, riwayat kehamilan, riwayat penyakit, dan riwayat persalinan. Disarankan meningkatkan kualitas pelayanan antenatal dengan memerhatikan faktor umur ibu dan riwayat persalinan, mengembangkan kegiatan audit maternal perinatal serta meningkatkan keterampilan petugas penolong persalinan. All developing countries including Indonesia seek to reach agreement the Millennium Development Goals (MDG’s. It is objectives include reducing neonatal mortality by 25 percent from 20 per 1,000 live birth to 15 per 1,000 live births. This study aimed to determine the relationship of maternal health services with neonatal mortality in East Lampung District in 2011. This study used case control design to compare between the groups of mother whom have neonatal deaths (cases and neonatal life (control in East Lampung District in
Yoon, Hye Kyung
Plain radiographs for infants in the neonatal intensive care unit are obtained using the portable X-ray equipment in order to evaluate the neonatal lungs and also to check the position of the tubes and catheters used for monitoring critically-ill neonates. Neonatal respiratory distress is caused by a variety of medical or surgical disease conditions. Clinical information about the gestational week, respiratory symptoms, and any events during delivery is essential for interpretation of the neonatal chest radiographs. Awareness of common chest abnormality in the prematurely born or term babies is also very important for chest evaluation in the newborn. Furthermore, knowledge about complications such as air leaks and bronchopulmonary dysplasia following treatment are required to accurately inform the clinicians. The purpose of this article was to briefly review radiographic findings of chest diseases in newborns that are relatively common in daily practice
Yoon, Hye Kyung [Dept. of Radiology, Kangwon National University Hospital, Chuncheon (Korea, Republic of)
Plain radiographs for infants in the neonatal intensive care unit are obtained using the portable X-ray equipment in order to evaluate the neonatal lungs and also to check the position of the tubes and catheters used for monitoring critically-ill neonates. Neonatal respiratory distress is caused by a variety of medical or surgical disease conditions. Clinical information about the gestational week, respiratory symptoms, and any events during delivery is essential for interpretation of the neonatal chest radiographs. Awareness of common chest abnormality in the prematurely born or term babies is also very important for chest evaluation in the newborn. Furthermore, knowledge about complications such as air leaks and bronchopulmonary dysplasia following treatment are required to accurately inform the clinicians. The purpose of this article was to briefly review radiographic findings of chest diseases in newborns that are relatively common in daily practice.
Nunes Magda Lahorgue
Full Text Available OBJECTIVE: To describe developmental characteristics, morphological aspects and incidence of temporal sharp transients (TST in normal preterm and term newborns at matched conceptional ages (CA. METHOD: Neonatal EEGs from two groups of normal newborns were evaluated in order to identify and characterize TST. Group I (n=40 consisted of newborns from 34 to 40 weeks of gestational age (GA that were submitted to a single EEG between 24 and 48 hours of life. Group II consisted of 10 preterm newborns with GA between 30-32 weeks, followed with a weekly EEG until they reached term. Morphology of TST was divided in 3 groups (temporal sawtooth, isolated transients or repetitive transients. TST index, density and total number were calculated in each polysomnography and related to sleep stages and CA. Laterality (right/left was also evaluated. The groups were compared at 34, 36, 38 and 40 weeks of CA. RESULTS: TST index and density decreased with the increase of CA in both groups (p<0.0001. The temporal sawtooth feature was registered in both groups only at 34 weeks. Although rare, repetitive and isolated TST were the most prevalent morphology between 36 - 40 weeks CA. Significant intragroup difference was observed in the comparison of TST density in REM and transitional sleep in GI. Moreover, isolated TST morphology was significant higher in GI at 34 weeks when compared to the others CA. No intragroup differences were observed on GII. No significant differences between the groups were observed considering TST number, index, density, morphology or laterality, at the matched CA. CONCLUSION: TST are normal features of neonatal EEG, as they are registered in normal newborns. Its incidence varies accordingly to morphology and they tend to disappear following the increase of CA. Temporal sawtooth appears more often in preterm newborns. Our results suggest that TST index, density and morphology variability may be a function of CA.
McParland, B.J.; Lee, R.
Neonates in the-Neonatal Intensive Care Unit (NICU) can receive large numbers of radiographs owing to the clinical conditions they may present. More neonatal radiation dosimetry data are required for three fundamental reasons: (1.) to aid in the establishment of reference dose levels for interinstitutional comparisons; (2.) to improve childhood cancer risk estimates following neonatal exposure; and (3.) to indicate appropriate directions for dose reduction. This paper describes an investigation of two different NICU radiological techniques with significantly different neonate doses. While patient-matched images taken with both techniques were assessed in a blind review, this component of the study is beyond the scope of this paper and is not discussed here. (author)
Jo, Dong Hyun; Park, Sung Wook; Cho, Chang Sik; Powner, Michael B; Kim, Jin Hyoung; Fruttiger, Marcus; Kim, Jeong Hun
Anti-vascular endothelial growth factor (VEGF) agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.
Dong Hyun Jo
Full Text Available Anti-vascular endothelial growth factor (VEGF agents are the mainstay treatment for various angiogenesis-related retinal diseases. Currently, bevacizumab, a recombinant humanized anti-VEGF antibody, is trailed in retinopathy of prematurity, a vasoproliferative retinal disorder in premature infants. However, the risks of systemic complications after intravitreal injection of anti-VEGF antibody in infants are not well understood. In this study, we show that intravitreally injected anti-VEGF antibody is transported into the systemic circulation into the periphery where it reduces brown fat in neonatal C57BL/6 mice. A considerable amount of anti-VEGF antibody was detected in serum after intravitreal injection. Furthermore, in interscapular brown adipose tissue, we found lipid droplet accumulation, decreased VEGF levels, loss of vascular network, and decreased expression of mitochondria-related genes, Ppargc1a and Ucp1, all of which are characteristics of "whitening" of brown fat. With increasing age and body weight, brown fat restored its morphology and vascularity. Our results show that there is a transient, but significant impact of intravitreally administered anti-VEGF antibody on brown adipose tissue in neonatal mice. We suggest that more attention should be focused on the metabolic and developmental significance of brown adipose tissue in bevacizumab treated retinopathy of prematurity infants.
Full Text Available BACKGROUND: It has been suggested that disturbed activity of the autonomic nervous system is one of the factors involved in gastroesophageal reflux (GER in adults. We sought to establish whether transient ANS dysfunction (as assessed by heart rate variability is associated with the occurrence of GER events in neonates during sleep and wakefulness. METHODS: Nineteen neonates with suspected GER underwent simultaneous, synchronized 12-hour polysomnography and esophageal multichannel impedance-pH monitoring. We compared changes in HRV parameters during three types of periods (control and prior to and during reflux with respect to the vigilance state. RESULTS: The vigilance state influenced the distribution of GER events (P<0.001, with 53.4% observed during wakefulness, 37.6% observed during active sleep and only 9% observed during quiet sleep. A significant increase in the sympathovagal ratio (+32%, P=0.013 was observed in the period immediately prior to reflux (due to a 15% reduction in parasympathetic activity (P=0.017, relative to the control period. This phenomenon was observed during both wakefulness and active sleep. CONCLUSION: Our results showed that GER events were preceded by a vigilance-state-independent decrease in parasympathetic tone. This suggests that a pre-reflux change in ANS activity is one of the factors contributing to the mechanism of reflux in neonates.
M. S. Tabib
Full Text Available Anaerobic bacteria are well known causes of sepsis in adults but there are few studies regarding their role in neonatal sepsis. In an attempt to define the incidence of neonatal anaerobic infections a prospective study was performed during one year period. A total number of 400 neonates under sepsis study were entered this investigation. Anaerobic as well as aerobic cultures were sent. The patients were subjected to comparison in two groups: anaerobic culture positive and anaerobic culture negative and this comparison were analyzed statistically. There were 7 neonates with positive anaerobic culture and 35 neonates with positive aerobic culture. A significant statistical relationship was found between anaerobic infections and abdominal distention and pneumonia. It is recommended for those neonates with abdominal distention and pneumonia refractory to antibiotic treatment to be started on antibiotics with anaerobic coverage.
Standardization of the experimental autoimmune myasthenia gravis (EAMG) model by immunization of rats with Torpedo californica acetylcholine receptors — Recommendations for methods and experimental designs
Losen, Mario; Martinez-Martinez, Pilar; Molenaar, Peter C.; Lazaridis, Konstantinos; Tzartos, Socrates; Brenner, Talma; Duan, Rui-Sheng; Luo, Jie; Lindstrom, Jon; Kusner, Linda
Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). This model covers cellular mechanisms involved in the immune response against the AChR, e.g. antigen presentation, T cell-help and regulation, B cell selection and differentiation into plasma cells. Our aim is to define standard operation procedures and recommendations for the rat EAMG model using purified AChR from the Torpedo californica electric organ, in order to facilitate more rapid translation of preclinical proof of concept or efficacy studies into clinical trials and, ultimately, clinical practice. PMID:25796590
Chikuie, Naoki; Ishida, Simon; Sato, Tomohiko; Furutama, Daisuke; Sugino, Shyouichi; Kimura, Humihiro; Hanafusa, Toshiaki
We present the case of a 56-year-old male with a syndrome involving the inappropriate secretion of antidiuretic hormone (SIADH), which developed during radiation therapy for invasive thymoma, complicated with myasthenia gravis (MG). Chest computed tomography revealed a huge mediastinal mass lesion spreading to the pulmonary artery, vena cava and pericardium. He was diagnosed with invasive thymoma, based on the pathological findings of a mediastinal tumor biopsy under computed tomography guidance. He received outpatient radiotherapy for the invasive thymoma, and two weeks after the initiation of radiation at a dose of 22 Gy, was admitted to our hospital because of hypercapnea due to weakness of the diaphragm and disturbance of consciousness. Laboratory examinations of the patient showed hyponatremia, plasma hypoosmolarity in the presence of concentrated urine and inappropriately increased concentration of the plasma antidiuretic hormone. He was also diagnosed as having myasthenia gravis, based on the existence of an anti-acetylcholine receptor antibody. The SIADH was treated by fluid restriction and sodium chloride, and MG was treated with plasma exchange and prednisolone. He recovered from respiratory failure, and his hyponatremia was improved. To our knowledge, this is a rare description of an invasive thymoma associated with SIADH. (author)
McGurgan, I J
The past decade has seen the widespread introduction of universal neonatal hearing screening (UNHS) programmes worldwide. Regrettably, such a programme is only now in the process of nationwide implementation in the Republic of Ireland and has been largely restricted to one screening modality for initial testing; namely transient evoked otoacoustic emissions (TEOAE). The aim of this study is to analyse the effects of employing a different screening protocol which utilises an alternative initial test, automated auditory brainstem response (AABR), on referral rates to specialist audiology services.
Titaley, Christiana R; Dibley, Michael J; Agho, Kingsley; Roberts, Christine L; Hall, John
Neonatal mortality accounts for almost 40 per cent of under-five child mortality, globally. An understanding of the factors related to neonatal mortality is important to guide the development of focused and evidence-based health interventions to prevent neonatal deaths. This study aimed to identify the determinants of neonatal mortality in Indonesia, for a nationally representative sample of births from 1997 to 2002. The data source for the analysis was the 2002-2003 Indonesia Demographic and Health Survey from which survival information of 15,952 singleton live-born infants born between 1997 and 2002 was examined. Multilevel logistic regression using a hierarchical approach was performed to analyze the factors associated with neonatal deaths, using community, socio-economic status and proximate determinants. At the community level, the odds of neonatal death was significantly higher for infants from East Java (OR = 5.01, p = 0.00), and for North, Central and Southeast Sulawesi and Gorontalo combined (OR = 3.17, p = 0.03) compared to the lowest neonatal mortality regions of Bali, South Sulawesi and Jambi provinces. A progressive reduction in the odds was found as the percentage of deliveries assisted by trained delivery attendants in the cluster increased. The odds of neonatal death were higher for infants born to both mother and father who were employed (OR = 1.84, p = 0.00) and for infants born to father who were unemployed (OR = 2.99, p = 0.02). The odds were also higher for higher rank infants with a short birth interval (OR = 2.82, p = 0.00), male infants (OR = 1.49, p = 0.01), smaller than average-sized infants (OR = 2.80, p = 0.00), and infant's whose mother had a history of delivery complications (OR = 1.81, p = 0.00). Infants receiving any postnatal care were significantly protected from neonatal death (OR = 0.63, p = 0.03). Public health interventions directed at reducing neonatal death should address community, household and individual level factors
Full Text Available BACKGROUND Neonatal conjunctivitis is eye discharge in neonates and it is a common infection in neonates in the first month of life. Worldwide, the incidence of neonatal conjunctivitis varies from 1% to 33% depending on the socioeconomic status of the people in the region. In India, the incidence varies from region to region from 0.9 to 35%. MATERIALS AND METHODS Single center prospective study. All neonates of age 0-30 days delivered and referred from neonatal ward of Chengalpattu Medical College and Hospital with complaints of eye swelling, redness, conjunctival discharge to the eye department for treatment are included in the study. RESULTS In this study, age group from 0-7 days were most commonly affected by neonatal conjunctivitis. Both eyes were commonly affected together. Neonates born by both LSCS and normal vaginal delivery were almost equally affected. The most common organism found in culture and Gram staining was staphylococci. CONCLUSION Neonatal conjunctivitis is more likely to be acquired postnatally. It acquires during the 1 st week and responds well to local application of antibiotics, which covers common causative bacteria.
Bjerregaard, P; Steinglass, R; Mutie, D M
In a house-to-house survey in Kilifi District, Kenya, mothers of 2556 liveborn children were interviewed about neonatal mortality, especially from neonatal tetanus (NNT). The crude birth rate was 60.5 per 1000 population, the neonatal mortality rate 21.1 and the NNT mortality rate 3.1 per 1000 li...... indicates that over the past decade the surveyed area has greatly reduced neonatal and NNT mortality. Possible strategies for accelerated NNT control have been identified by the survey....
Chang, Alvin S M; Berry, Andrew; Jones, Lisa J; Sivasangari, Subramaniam
Maternal antenatal transfers provide better neonatal outcomes. However, there will inevitably be some infants who require acute transport to a neonatal intensive care unit (NICU). Because of this, many institutions develop services to provide neonatal transport by specially trained health personnel. However, few studies report on relevant clinical outcomes in infants requiring transport to NICU. To determine the effects of specialist transport teams compared with non-specialist transport teams on the risk of neonatal mortality and morbidity among high-risk newborn infants requiring transport to neonatal intensive care. We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 7), MEDLINE (1966 to 31 July 2015), EMBASE (1980 to 31 July 2015), CINAHL (1982 to 31 July 2015), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. randomised, quasi-randomised or cluster randomised controlled trials. neonates requiring transport to a neonatal intensive care unit. transport by a specialist team compared to a non-specialist team. any of the following outcomes - death; adverse events during transport leading to respiratory compromise; and condition on admission to the neonatal intensive care unit. The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size estimated and reported as risk ratio (RR), risk difference (RD), number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH) and mean difference (MD) for continuous outcomes. Data from cluster randomised trials were not combined for analysis. One trial met the inclusion criteria of this review but was considered ineligible owing to
V. V. Moskalev
Full Text Available Objective: to evaluate the efficiency of hydroxyethyl starch solution (6% refortane, Berlin-Chemie versus fresh frozen plasma used to correct neonatal hypovolemia.Materials and methods. In 12 neonatal infants with hypoco-agulation, hypovolemia was corrected with fresh frozen plasma (10 ml/kg body weight. In 13 neonates, it was corrected with 6% refortane infusion in a dose of 10 ml/kg. Doppler echocardiography was used to study central hemodynamic parameters and Doppler study was employed to examine regional blood flow in the anterior cerebral and renal arteries.Results. Infusion of 6% refortane and fresh frozen plasma at a rate of 10 ml/hour during an hour was found to normalize the parameters of central hemodynamics and regional blood flow.Conclusion. Comparative analysis of the findings suggests that 6% refortane is the drug of choice in correcting neonatal hypovolemia. Fresh frozen plasma should be infused in hemostatic disorders.
Ulusoy, Canan; Çavuş, Filiz; Yılmaz, Vuslat; Tüzün, Erdem
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ), characterized with muscle weakness. While MG develops due to acetylcholine receptor (AChR) antibodies in most patients, antibodies to muscle-specific receptor tyrosine kinase (MuSK) or low-density lipoprotein receptor-related protein 4 (LRP4) may also be identified. Experimental autoimmune myasthenia gravis (EAMG) has been previously induced by both LRP4 immunization and passive transfer of LRP4 antibodies. Our aim was to confirm previous results and to test the pathogenic effects of LRP4 immunization in a commonly used mouse strain C57BL/6 (B6) using a recombinantly expressed human LRP4 protein. B6 mice were immunized with human LRP4 in CFA, Torpedo Californica AChR in CFA or only CFA. Clinical and pathogenic aspects of EAMG were compared among groups. LRP4- and AChR-immunized mice showed comparable EAMG clinical severity. LRP4-immunized mice displayed serum antibodies to LRP4 and NMJ IgG and complement factor C3 deposits. IgG2 was the dominant anti-LRP4 isotype. Cultured lymph node cells of LRP4- and AChR-immunized mice gave identical pro-inflammatory cytokine (IL-6, IFN-γ and IL-17) responses to LRP4 and AChR stimulation, respectively. Our results confirm the EAMG-inducing action of LRP4 immunization and identify B6 as a LRP4-EAMG-susceptible mouse strain. Demonstration of complement fixing anti-LRP4 antibodies in sera and complement/IgG deposits at the NMJ of LRP4-immunized mice indicates complement activation as a putative pathogenic mechanism. We have thus developed a practical LRP4-induced EAMG model using a non-conformational protein and a widely available mouse strain for future investigation of LRP4-related MG.
The purpose of this document is to address the current lack of consensus regarding the management of hyperbilirubinaemia in neonates in South Africa. If left untreated, severe neonatal hyperbilirubinaemia may cause kernicterus and ultimately death and the severity of neonatal jaundice is often underestimated clinically.
JORGE S. REIS FILHO
Full Text Available Thymomas are tumors characterized by a remarkable morphological heterogeneity and variable clinical behavior. This tumor has unique clinical associations, most notably with hematological abnormalities and myasthenia gravis. According with the Müller-Hermelink criteria, there are significant differences between the histological types of thymomas and the association with myasthenia gravis. Among the different histological types, medullary thymoma is the least frequent variant associated with this autoimmune disease. In this report we describe a case of medullary thymoma presenting in a 71-year- old woman with a myasthenic syndrome.Os timomas são tumores caracterizados por grande heterogeneidade morfológica e comportamento clínico variável. Este tumor apresenta associações clínicas singulares, principalmente com doenças hematológicas e com a miastenia gravis. De acordo com a classificação de Müller-Hermelink, existem diferenças significativas entre as variedades histológicas dos timomas e sua associação com a miastenia gravis. Entre os diferentes tipos histológicos, o timoma medular é a variante menos frequentemente associada com esta doença autoimune. Neste relato, nós descrevemos caso de timoma medular em uma paciente de 71 anos de idade com síndrome miastênica.
Garg, Bhawan Deep; Kabra, Nandkishor S; Balasubramanian, Haribalakrishna
Neonatal hyperbilirubinemia (NNH) is one of the leading causes of admissions in nursery throughout the world. It affects approximately 2.4-15% of neonates during the first 2 weeks of life. To evaluate the role of massage therapy for reduction of NNH in both term and preterm neonates. The literature search was done for various randomized control trials (RCTs) by searching the Cochrane Library, PubMed, and EMBASE. This review included total of 10 RCTs (two in preterm neonates and eight in term neonates) that fulfilled inclusion criteria. In most of the trials, Field massage was given. Six out of eight trials reported reduction in bilirubin levels in term neonates. However, only one trial (out of two) reported significant reduction in bilirubin levels in preterm neonates. Both trials in preterm neonates and most of the trials in term neonates (five trials) reported increased stool frequencies. Role of massage therapy in the management of NNH is supported by the current evidence. However, due to limitations of the trials, current evidences are not sufficient to use massage therapy for the management of NNH in routine practice.
Bruno, C J; Johnston, L; Lee, C; Bernstein, P S; Goffman, D
Our goal was to garner opinions regarding neonatal resuscitation training for obstetric physicians. We sought to evaluate obstacles to neonatal resuscitation training for obstetric physicians and possible solutions for implementation challenges. We distributed a national survey via email to all neonatal-perinatal medicine fellowship directors and obstetrics & gynecology residency program directors in the United States. This survey was designed by a consensus method. Ninety-eight (53%) obstetric and fifty-seven (51%) neonatal program directors responded to our surveys. Eighty-eight percent of neonatologists surveyed believe that obstetricians should be neonatal resuscitation program (NRP) certified. The majority of surveyed obstetricians (>89%) believe that obstetricians should have some neonatal resuscitation training. Eighty-six percent of obstetric residents have completed training in NRP, but only 19% of obstetric attendings are NRP certified. Major barriers to NRP training that were identified include time, lack of national requirement, lack of belief it is helpful, and cost. Most obstetric attendings are not NRP certified, but the majority of respondents believe that obstetric providers should have some neonatal resuscitation training. Our study demonstrates that most respondents support a modified neonatal resuscitation course for obstetric physicians.
Afrasiabi, Narges; Mohagheghi, Parisa; Kalani, Majid; Mohades, Gholam; Farahani, Zahra
High risk pregnancies increase the risk of neonatal mortality and morbidity. In order to identify the influence of pregnancy complications on the period of neonatal stay in Neonatal Intensive Care Units (NICUs), an analysis has been carried out in our center. In a cross-sectional-descriptive analytical study, the data including NICU length of stay was gathered from 526 medical records of neonates. We also assessed their maternal complications such as premature rapture of membranes (PROM), urinary tract infection (UTI), preeclampsia, oligohydramnios, and twin/triplet pregnancy. Finally we analyzed the relation between variables by SPSS statistics software version 19. The level of significance was considered PUTI (P=0.02), multiple gestation (P=0.03), and oligohydramnios (P=0.003). We found a positive correlation between numbers of gestation and length of NICU stay (P=0.03). A positive correlation existed between neonatal complication and length of NICU stay (P<0.001). By increasing maternal health level and prenatal care services, neonatal outcome can be improved and length of stay in NICUs decreased.
Background Neonatal jaundice affects one in two infants globally. The jaundice is the result of an accumulation of bilirubin as foetal haemoglobin is metabolised by the immature liver. High serum levels of bilirubin result in lethargy, poor feeding and kernicterus of the infant. Aim The main aim of this article was to determine the prevalence of neonatal jaundice and secondly to explore its risk factors in healthy term neonates. Setting Maternity ward, National District Hospital, Bloemfontein, South Africa. Methods In this cross-sectional study, mothers and infants were conveniently sampled after delivery and before discharge. The mothers were interviewed and their case records were reviewed for risk factors for neonatal jaundice and the clinical appearance and bilirubin levels of the infants were measured with a non-invasive transcutaneous bilirubin meter. Results A total of 96 mother-infant pairs were included in the study. The prevalence of neonatal jaundice was 55.2%; however, only 10% of black babies who were diagnosed with jaundice appeared clinically jaundiced. Normal vaginal delivery was the only risk factor associated with neonatal jaundice. Black race and maternal smoking were not protective against neonatal jaundice as in some other studies. Conclusion More than half (55.2%) of healthy term neonates developed neonatal jaundice. As it is difficult to clinically diagnose neonatal jaundice in darker pigmented babies, it is recommended that the bilirubin level of all babies should be checked with a non-invasive bilirubin meter before discharge from hospital or maternity unit as well as during the first clinic visit on day 3 after birth.
Pierce, Angela N.; Zhang, Zhen; Fuentes, Isabella M.; Wang, Ruipeng; Ryals, Janelle M.; Christianson, Julie A.
Abstract Experiencing early life stress or injury increases a woman's likelihood of developing vulvodynia and concomitant dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. To investigate the outcome of neonatal vaginal irritation (NVI), female mouse pups were administered intravaginal zymosan on postnatal days 8 and 10 and were assessed as adults for vaginal hypersensitivity by measuring the visceromotor response to vaginal balloon distension (VBD). Western blotting and calcium imaging were performed to measure transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) in the vagina and innervating primary sensory neurons. Serum corticosterone (CORT), mast cell degranulation, and corticotropin-releasing factor receptor 1 (CRF1) expression were measured as indicators of peripheral HPA axis activation. Colorectal and hind paw sensitivity were measured to determine cross-sensitization resulting from NVI. Adult NVI mice had significantly larger visceromotor response during VBD than naive mice. TRPA1 protein expression was significantly elevated in the vagina, and calcium transients evoked by mustard oil (TRPA1 ligand) or capsaicin (TRPV1 ligand) were significantly decreased in dorsal root ganglion from NVI mice, despite displaying increased depolarization-evoked calcium transients. Serum CORT, vaginal mast cell degranulation, and CRF1 protein expression were all significantly increased in NVI mice, as were colorectal and hind paw mechanical and thermal sensitivity. Neonatal treatment with a CRF1 antagonist, NBI 35965, immediately before zymosan administration largely attenuated many of the effects of NVI. These results suggest that NVI produces chronic hypersensitivity of the vagina, as well as of adjacent visceral and distant somatic structures, driven in part by increased HPA axis activation. PMID:26098441
Vinge, Lotte; Jakobsen, Johannes; Pedersen, Asger Roer; Andersen, Henning
In patients with myasthenia gravis (MG), muscle strength is expected to decrease gradually during the day due to physical activities. Isometric muscle strength at the shoulder, knee, and ankle was determined in 10 MG patients (MGFA class II-IV) who were receiving usual medical treatment and in 10 control subjects. To determine diurnal and day-to-day variation, muscle strength was measured 4 times during day 1 and once at day 2. Knee extension strength decreased during the day in both patients and controls. Neither diurnal nor day-to-day variation of muscle strength was higher in patients compared with controls. Patients with mild to moderate MG did not have increased variation of isometric muscle strength during the day or from day-to-day compared with controls. This suggests that isometric muscle performance can be determined with high reproducibility in similar groups of MG patients without regard to time of day. © 2015 Wiley Periodicals, Inc.
Full Text Available Biomarkers that assess treatment response for patients with the autoimmune disorder, myasthenia gravis (MG, have not been evaluated to a significant extent. We hypothesized the pro-inflammatory cytokine, osteopontin (OPN, may be associated with variability of response to glucocorticoids (GCs in patients with MG. A cohort of 250 MG patients treated with standardized protocol of GCs was recruited, and plasma OPN and polymorphisms of its gene, secreted phosphoprotein 1 (SPP1, were evaluated. Mean OPN levels were higher in patients compared to healthy controls. Carriers of rs11728697*T allele (allele definition: one of two or more alternative forms of a gene were more frequent in the poorly GC responsive group compared to the GC responsive group indicating an association of rs11728697*T allele with GC non-responsiveness. One risk haplotype (AGTACT was identified associated with GC non-responsiveness compared with GC responsive MG group. Genetic variations of SPP1 were found associated with the response to GC among MG patients.
Hokezu, Youichi; Kaseda, Syun; Arimura, Kimiyoshi; Osame, Mitsuhiro; Baba, Kuniaki (Kagoshima Univ. (Japan). Faculty of Medicine); Ohkubo, Koichi; Hagiwara, Hiroshi
Seven patients with myasthenia gravis (MG) were examined to find thymus or thymoma employing chest radiographs, computed tomography (CT), pneumomediastinography (PMG), computed tomography after pneumomediastinography (PMG-CT) and magnetic resonance imaging (MRI). X-ray CT examination could reveal thymus only in half out of 6 cases scanned. On the other hand, MRI confirmed thymus or thymoma in 6 out of 7 patients. PMG and PMG-CT confirmed thymus or thymoma clearly in all of the 4 cases studied. PMG and PMG-CT examinations revealed thymus or thymoma more clearly than MRI. MRI is, however, an examination causing no pain to the patients and also more superior to X-ray CT in distinguishing between a thymus and mediastinal fat or vascular structure. In addition, MRI could reveal even capsules in thymoma which were never revealed by X-ray CT. We concluded that MRI could be an alternative method to CT and PMG in detection of thymus or thymoma in MG. (author).
Hokezu, Youichi; Kaseda, Syun; Arimura, Kimiyoshi; Osame, Mitsuhiro; Baba, Kuniaki; Ohkubo, Koichi; Hagiwara, Hiroshi.
Seven patients with myasthenia gravis (MG) were examined to find thymus or thymoma employing chest radiographs, computed tomography (CT), pneumomediastinography (PMG), computed tomography after pneumomediastinography (PMG-CT) and magnetic resonance imaging (MRI). X-ray CT examination could reveal thymus only in half out of 6 cases scanned. On the other hand, MRI confirmed thymus or thymoma in 6 out of 7 patients. PMG and PMG-CT confirmed thymus or thymoma clearly in all of the 4 cases studied. PMG and PMG-CT examinations revealed thymus or thymoma more clearly than MRI. MRI is, however, an examination causing no pain to the patients and also more superior to X-ray CT in distinguishing between a thymus and mediastinal fat or vascular structure. In addition, MRI could reveal even capsules in thymoma which were never revealed by X-ray CT. We concluded that MRI could be an alternative method to CT and PMG in detection of thymus or thymoma in MG. (author)
Flores, F X; Ojeda, F J; Calhoun, D A
Reports of Bartter syndrome in premature neonates are rare. We describe the presentation and clinical course of a neonate born at 25.6 weeks estimated gestational age with polyuria, hyponatremia, hypokalemia and hypercalciuria ,who was diagnosed with neonatal Bartter syndrome. The evaluation, diagnosis and management of neonatal Bartter syndrome in this premature neonate are discussed.
Kanakatti Shankar, Roopa; Pihoker, Catherine; Dolan, Lawrence M; Standiford, Debra; Badaru, Angela; Dabelea, Dana; Rodriguez, Beatriz; Black, Mary Helen; Imperatore, Giuseppina; Hattersley, Andrew; Ellard, Sian; Gilliam, Lisa K
Neonatal diabetes mellitus (NDM) is defined as diabetes with onset before 6 months of age. Nearly half of individuals with NDM are affected by permanent neonatal diabetes mellitus (PNDM). Mutations in KATP channel genes (KCNJ11, ABCC8) and the insulin gene (INS) are the most common causes of PNDM. To estimate the prevalence of PNDM among SEARCH for Diabetes in Youth (SEARCH) study participants (2001-2008) and to identify the genetic mutations causing PNDM. SEARCH is a multicenter population-based study of diabetes in youth diabetes before 6 months of age were invited for genetic testing for mutations in the KCNJ11, ABCC8, and INS genes. Of the 15,829 SEARCH participants with diabetes, 39 were diagnosed before 6 months of age. Thirty-five of them had PNDM (0.22% of all diabetes cases in SEARCH), 3 had transient neonatal diabetes that had remitted by 18 months and 1 was unknown. The majority of them (66.7%) had a clinical diagnosis of type1 diabetes by their health care provider. Population prevalence of PNDM in youth US based on the frequency of PNDM in SEARCH. Patients with NDM are often misclassified as having type1 diabetes. Widespread education is essential to encourage appropriate genetic testing and treatment of NDM. © 2012 John Wiley & Sons A/S.
Full Text Available est (RST is the most commonly used electrodiagnostic test to asses the defect of neuromuscular transmission, which is reported to be positive in the diffuse and restricted ocular forms 60-95% and 14-50%, respectively. In a cross-sectional study, to determine the efficacy of repetitive stimulation test in myasthenia gravis, we evaluated the results in 30 cases who were hospitalized in Imam Khomeini Hospital during 1996-1999. Patients were first selected clinically and then confirmed by Tensilon test.Various clinical types including generalized and restricted ocular forms with different severity and duration were entered in this study. Considering the fact that the positiveness of the test is enhanced by assessment of more muscle groups, we evaluated decremental response in the facial, proximal and distal muscles of limbs. 90% of patients had the generalized form of the disease, whereas ocular myasthenia gravis was seen only in 10% of the cases. 74% of females and 73% of males showed positive response (overall: 73.3%. No significant association was found between the positive response, and age and sex. Peaks of incidences of the disease for the males were in fourth and sixth decades and for the females in thired decades
Mantegazza, Renato; Bonanno, Silvia; Camera, Giorgia; Antozzi, Carlo
Myasthenia gravis (MG) is an autoimmmune disease in which autoantibodies to different antigens of the neuromuscular junction cause the typical weakness and fatigability. Treatment includes anticholinesterase drugs, immunosuppression, immunomodulation, and thymectomy. The autoimmune response is maintained under control by corticosteroids frequently associated with immunosuppressive drugs, with improvement in the majority of patients. In case of acute exacerbations with bulbar symptoms or repeated relapses, modulation of autoantibody activity by plasmapheresis or intravenous immunoglobulins provides rapid improvement. Recently, techniques removing only circulating immunoglobulins have been developed for the chronic management of treatment-resistant patients. The rationale for thymectomy relies on the central role of the thymus. Despite the lack of controlled studies, thymectomy is recommended as an option to improve the clinical outcome or promote complete remission. New videothoracoscopic techniques have been developed to offer the maximal surgical approach with the minimal invasiveness and hence patient tolerability. The use of biological drugs such as anti-CD20 antibodies is still limited but promising. Studies performed in the animal model of MG demonstrated that several more selective or antigen-specific approaches, ranging from mucosal tolerization to inhibition of complement activity or cellular therapy, might be feasible. Investigation of the transfer of these therapeutic approaches to the human disease will be the challenge for the future. PMID:21552317
Chawes, Bo L.K.; Stokholm, Jakob; Bønnelykke, Klaus
Background: Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced...... lung function. ObjectiveWe sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation. Methods: Plasma levels of high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-6, TNF-α, and CXCL8 (IL-8) were measured at age 6 months in 300 children....... Results: The neonatal forced expiratory volume at 0.5 seconds was inversely associated with hs-CRP (β-coefficient, −0.12; 95% CI, −0.21 to −0.04; P approach, including hs-CRP, IL-6...
Chen-Hong Wang; Li-Zhong Du; Xiao-Lu Ma; Li-Ping Shi; Xiao-Mei Tong; Hong Liu; Guo-Fang Ding
Background:Globally,the proportion of child deaths that occur in the neonatal period remains a high level of 37-41％.Differences of cause in neonate death exist in different regions as well as in different economic development countries.The specific aim of this study was to investigate the causes,characteristics,and differences of death in neonates during hospitalization in the tertiary Neonatal Intensive Care Unit (NICU) of China.Methods:All the dead neonates admitted to 26 NICUs were included between January 1,2011,and December 31,2011.All the data were collected retrospectively from clinical records by a designed questionnaire.Data collected from each NICU were delivered to the leading institution where the results were analyzed.Results:A total of 744 newborns died during the l-year survey,accounting for 1.2％ of all the neonates admitted to 26 NICUs and 37.6％ of all the deaths in children under 5 years of age in these hospitals.Preterm neonate death accounted for 59.3％ of all the death.The leading causes of death in preterm and term infants were pulmonary disease and infection,respectively.In early neonate period,pulmonary diseases (56.5％) occupied the largest proportion ofpreterm deaths while infection (27％) and neurologic diseases (22％) were the two main causes of term deaths.In late neonate period,infection was the leading cause of both preterm and term neonate deaths.About two-thirds of neonate death occurred after medical care withdrawal.Of the cases who might survive if receiving continuing treatment,parents' concern about the long-term outcomes was the main reason of medical care withdrawal.Conclusions:Neonate death still accounts for a high proportion of all the deaths in children under 5 years of age.Our study showed the majority of neonate death occurred in preterm infants.Cause of death varied with the age of death and gestational age.Accurate and prompt evaluation of the long-term outcomes should be carried out to guide the critical
Full Text Available Abstract Background Neonatal mortality accounts for almost 40 per cent of under-five child mortality, globally. An understanding of the factors related to neonatal mortality is important to guide the development of focused and evidence-based health interventions to prevent neonatal deaths. This study aimed to identify the determinants of neonatal mortality in Indonesia, for a nationally representative sample of births from 1997 to 2002. Methods The data source for the analysis was the 2002–2003 Indonesia Demographic and Health Survey from which survival information of 15,952 singleton live-born infants born between 1997 and 2002 was examined. Multilevel logistic regression using a hierarchical approach was performed to analyze the factors associated with neonatal deaths, using community, socio-economic status and proximate determinants. Results At the community level, the odds of neonatal death was significantly higher for infants from East Java (OR = 5.01, p = 0.00, and for North, Central and Southeast Sulawesi and Gorontalo combined (OR = 3.17, p = 0.03 compared to the lowest neonatal mortality regions of Bali, South Sulawesi and Jambi provinces. A progressive reduction in the odds was found as the percentage of deliveries assisted by trained delivery attendants in the cluster increased. The odds of neonatal death were higher for infants born to both mother and father who were employed (OR = 1.84, p = 0.00 and for infants born to father who were unemployed (OR = 2.99, p = 0.02. The odds were also higher for higher rank infants with a short birth interval (OR = 2.82, p = 0.00, male infants (OR = 1.49, p = 0.01, smaller than average-sized infants (OR = 2.80, p = 0.00, and infant's whose mother had a history of delivery complications (OR = 1.81, p = 0.00. Infants receiving any postnatal care were significantly protected from neonatal death (OR = 0.63, p = 0.03. Conclusion Public health interventions directed at reducing neonatal death should
Arthurs, Owen J.; Graves, Martin J.; Lomas, David J.; Edwards, Andrea; Austin, Topun
Improved neonatal survival rates and antenatal diagnostic imaging is generating a growing demand for postnatal MRI examinations. Neonatal brain MRI is now becoming standard clinical care in many settings, but with the exception of some research centres, the technique has not been optimised for imaging neonates and small children. Here, we review some of the challenges involved in neonatal MRI, including recent advances in overall MR practicality and nursing practice, to address some of the ways in which the MR experience could be made more neonate-friendly. (orig.)
Meoded, A.; Poretti, A.; Northington, F.J.; Tekes, A.; Intrapiromkul, J.; Huisman, T.A.G.M.
Susceptibility weighted imaging (SWI) is a well-established magnetic resonance technique, which is highly sensitive for blood, iron, and calcium depositions in the brain and has been implemented in the routine clinical use in both children and neonates. SWI in neonates might provide valuable additional diagnostic and prognostic information for a wide spectrum of neonatal neurological disorders. To date, there are few articles available on the application of SWI in neonatal neurological disorders. The purpose of this article is to illustrate and describe the characteristic SWI findings in various typical neonatal neurological disorders.
Meoded, A.; Poretti, A. [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Northington, F.J. [Division of Neonatology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Tekes, A.; Intrapiromkul, J. [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States); Huisman, T.A.G.M., E-mail: email@example.com [Division of Pediatric Radiology and Division of Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD (United States)
Susceptibility weighted imaging (SWI) is a well-established magnetic resonance technique, which is highly sensitive for blood, iron, and calcium depositions in the brain and has been implemented in the routine clinical use in both children and neonates. SWI in neonates might provide valuable additional diagnostic and prognostic information for a wide spectrum of neonatal neurological disorders. To date, there are few articles available on the application of SWI in neonatal neurological disorders. The purpose of this article is to illustrate and describe the characteristic SWI findings in various typical neonatal neurological disorders.
Hanlon, Lauren A.; Huh, Jimmy W.
Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312
Full Text Available Abstract Introduction The association of thymoma with myasthenia gravis (MG is well known. Thymoma with sarcoidosis however, is very rare. We presented an interesting case with coexisting thymoma, MG and sarcoidosis. Case presentation A 59-year-old female patient with a history of sarcoidosis was admitted to the hospital with a one-day history of sudden onset of right-sided partial ptosis and diplopia. Neurosarcoidosis with cranial nerve involvement was considered, but was ruled out by the clinical findings, and MG was confirmed by the positive tensilon test, electrophysiological findings and positive acetylcholine receptor binding antibodies. On further evaluation, a CT chest scan showed a left anterior mediastinal mass and bilateral lymphadenopathy. Post surgical diagnosis confirmed the thymoma and sarcoidosis in the lymph nodes. Conclusion When two or more diseases of undetermined origin are found together, several interesting questions are raised. It is important to first confirm the diagnoses individually. Immunologic mechanisms triggering the occurrence of these diagnoses together, are difficult to address. Although the coexistence of thymoma, MG and sarcoidosis may be coincidental, it is noteworthy to report this case because of the multiple interesting features observed as well as the rarity of occurrence.
Blanco de la Fuente, María Isabel
El motivo que ha llevado a la realización de este trabajo fin de grado sobre el tema de la ICTERICIA NEONATAL se debe a la elevada frecuencia de su aparición en la población. Un porcentaje elevado de RN la padecen al nacer siendo, en la mayor parte de los casos, un proceso fisiológico resuelto con facilidad debido a una inmadurez del sistema hepático y a una hiperproducción de bilirrubina. La ictericia neonatal es la pigmentación de color amarillo de la piel y mucosas en ...
Hamza, Mostafa; Hamza, Mohammad
This paper describes our leading experience in the clinical application of laser in the treatment of neonatal jaundice. Currently, the irradiation of jaundiced infants during neonatal life to fluorescent light is the most common treatment of neonatal hyperbilirubinemia. The authors have investigated the photodegradation of bilirubin by laser in vitro and in Gunn rats before embarking on its clinical application in the treatment of jaundice in the new born child. This work was done to study the theraputic effect of laser compared to the currently used phototherapy in the treatment of neonatal jaundice. We selected 16 full term neonates with jaundice to be the subject of this study. The neonates of the study were devided into two groups. The first group was treated with continuous phototherapy . The second group recieved photoradiation therapy with gas laser The laser used was a CW argon-ion laser tuned to oscillate at 488.0 nm wavelength. This wavelength selection was based on our previous studies on the effect of laser irradiation of Gunn rats at different wavelengths. Comparison of the results of both methods of treatment will be reported in detail. The advantages and limitations of laser photoradiation therapy for neonatal jaundice will be discussed.
Khong, P.L.; Lam, B.C.C.; Tung, H.K.S.; Wong, V.; Chan, F.L.; Ooi, G.C.
We present the magnetic resonance imaging (MRI) findings in neonatal encephalopathy, including hypoxic-ischaemic encephalopathy, perinatal/neonatal stroke, metabolic encephalopathy from inborn errors of metabolism, congenital central nervous system infections and birth trauma. The applications of advanced MRI techniques, such as diffusion-weighted imaging and magnetic resonance spectroscopy are emphasized
Full Text Available Taylor Sawyer, Rachel A Umoren, Megan M Gray Department of Pediatrics, Division of Neonatology, Neonatal Education and Simulation-based Training (NEST Program, University of Washington School of Medicine, Seattle, WA, USA Abstract: Each year in the US, some four hundred thousand newborns need help breathing when they are born. Due to the frequent need for resuscitation at birth, it is vital to have evidence-based care guidelines and to provide effective neonatal resuscitation training. Every five years, the International Liaison Committee on Resuscitation (ILCOR reviews the science of neonatal resuscitation. In the US, the American Heart Association (AHA develops treatment guidelines based on the ILCOR science review, and the Neonatal Resuscitation Program (NRP translates the AHA guidelines into an educational curriculum. In this report, we review recent advances in neonatal resuscitation training and practice. We begin with a review of the new 7th edition NRP training curriculum. Then, we examine key changes to the 2015 AHA neonatal resuscitation guidelines. The four components of the NRP curriculum reviewed here include eSim®, Performance Skills Stations, Integrated Skills Station, and Simulation and Debriefing. The key changes to the AHA neonatal resuscitation guidelines reviewed include initial steps of newborn care, positive-pressure ventilation, endotracheal intubation and use of laryngeal mask, chest compressions, medications, resuscitation of preterm newborns, and ethics and end-of-life care. We hope this report provides a succinct review of recent advances in neonatal resuscitation. Keywords: neonatal resuscitation, Neonatal Resuscitation Program, NRP, simulation, deliberate practice, debriefing, eSIM