Inflammatory Muscle Diseases Young, Pablo; Finn, Barbara C; Reisin, Ricardo ...
New England journal of medicine/The New England journal of medicine,
07/2015, Letnik:
373, Številka:
4
Journal Article
Recenzirano
Odprti dostop
To the Editor:
In the review article on inflammatory muscle diseases, Dalakas (April 30 issue)
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outlines four major subtypes. In 1998, Gherardi et al. described a new but underrecognized clinical ...variant, called macrophagic myofasciitis,
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a condition that presents as diffuse myalgias of variable intensity associated with chronic fatigue. Myalgia predominantly affects the lower limbs and is often aggravated by exercise. It is associated with arthralgias in 50 to 60% of patients, as well as fever in 30% of patients.
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Results on electromyography may be myopathic, and creatine kinase levels may be elevated in up to 50% of patients.
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This disease . . .
Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can ...therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.
Time delays in the diagnosis and treatment of Fabry disease Reisin, Ricardo; Perrin, Amandine; García‐Pavía, Pablo
International journal of clinical practice,
January 2017, 2017-Jan, 2017-01-00, 20170101, Letnik:
71, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary
Background
The high variability in clinical manifestations of Fabry disease can lead to delays between symptom onset and correct diagnosis, and between correct diagnosis and initiation of ...enzyme replacement therapy. We investigated whether these delays have improved in recent years.
Methods
Data were analysed from the Fabry Outcome Survey (FOS; Shire; extracted August 2013) for “index patients”, defined as the first patient diagnosed with Fabry disease from a family with several or no additional members registered in FOS.
Results
Periods analysed: 2001‐2006 vs. 2007‐2013, in patients overall and from Europe vs. the rest of the world (ROW). Overall, 598 patients were diagnosed within the study periods. Median age (95% CI) at symptom onset in 2001‐2006 and 2007‐2013 was 7.0 (5.0‐11.0) and 9.0 (6.0‐11.0) in children, and 21.0 (15.0‐28.0) and 31.0 (26.0‐35.0) in adults, respectively. Overall, the delay in diagnosis did not improve, despite showing a trend towards earlier diagnosis in adults (median 14.0 95% CI 9.0‐20.0 vs. 10.5 8.0‐13.0 years) and children (5.0 1.0‐9.0 vs. 4.0 0.0‐8.0 years). In contrast, the delay in treatment onset significantly decreased from 2001‐2006 to 2007‐2013 in children (4.3 2.0‐7.0 vs. 1.0 0.8‐1.4 year; P<.001) and adults (2.1 1.3‐3.2 vs. 0.9 0.8‐1.1 years; P<.001). Geographically, the delay in treatment onset significantly decreased in the ROW among children (5.3 4.2‐8.0 vs. 1.0 0.8‐1.4 year; P<.001) and adults (5.4 4.8‐6.0 vs. 1.1 0.9‐1.1 years; P<.001), but it did not change in Europe.
Conclusion
We found that the delay in diagnosis has not improved substantially whereas the delay in treatment onset has improved in recent years.
The clinical use of agalsidase alfa as enzyme replacement therapy (ERT) for Fabry disease (FD) has spread since 2001, and a large body of evidence of its effectiveness has been collected. This review ...presents the clinical and laboratory results achieved with agalsidase alfa, which has been published in the literature. Agalsidase alfa infusion slows down or stops the progression of renal damage, expressed by reduction or stabilization of the annual decline of the glomerular filtration rate; yearly decrease of glomerular filtration rate (slope) sometimes is reduced until its stabilization. ERT prevents or reduces the occurrence of hypertrophic cardiomyopathy or slows the increase over time if it is already present. Moreover, regarding neurological manifestations, ERT improves neuropathic pain and quality of life, and recent data indicated that it may also prevent the burden of cerebrovascular disease. In addition to ERT's clinical benefits, crucial topics like the most appropriate time to start therapy and the role of anti-drug antibodies (ADA) are analyzed. Treatment with agalsidase alfa in patients with FD substantially improves their outcomes and enhances their quality of life in patients with FD.
Neuropathic pain is one of the key features of the classical phenotype of Fabry disease (FD). Acid sensing ion channels (ASICs) are H+-gated cation channels, which belong to the epithelial sodium ...channel/DeGenerin superfamily, sensitive to the diuretic drug Amiloride. Molecular cloning has identified several distinct ASIC subunits. In particular the ASIC1a subunit has been associated to pain and its upregulation has been documented in animal models of pain. We analyzed the expression of ASIC1a channels in cellular models that mimic the accumulation of glycosphingolipids in FD (FD-GLs) like Gb3, and LysoGb3. We used mouse primary neurons from brain cortex and hippocampus -supraspinal structures that accumulate FD-GLs-, as well as HEK293 cells. Incubation with Gb3, lysoGb3 and the inhibitor (1-deoxy-galactonojirymicin, DJG) of the enzyme α-galactosidase A (Gla) lead to the upregulation of ASIC1a channels. In addition, activation of ASIC1a results in the activation of the MAPK ERK pathway, a signaling pathway associated with pain. Moreover, accumulation of glycosphingolipids results in activation of ERK, an effect that was prevented by blocking ASIC1a channels with the specific blocker Psalmotoxin. Our results suggest that FD-GLs accumulation and triggering of the ERK pathway via ASIC channels might be involved in the mechanism responsible for pain in FD, thus providing a new therapeutic target for pain relief treatment.
•ASIC1a protein and mRNA levels are upregulated via FD-associated glycosphingolipids.•ASIC1a upregulation via FD-GLs is associated to increase in ERK-signaling pathway.•Increase ERK signaling via FD-GLs can be prevented via ASIC1a inhibitors.
Patient registries provide long-term, real-world evidence that aids the understanding of the natural history and progression of disease, and the effects of treatment on large patient populations with ...rare diseases. The year 2021 marks the 20th anniversary of the Fabry Outcome Survey (FOS), an international, multicenter, observational registry (NCT03289065). The primary aims of FOS are to broaden the understanding of Fabry disease (FD), an X-linked lysosomal storage disorder, and to improve the clinical management of affected patients. Here, we review the history of FOS and the analyses and publications disseminated from the registry, and we discuss the contributions FOS studies have made in understanding FD. FOS was initiated in April 2001 and, as of January 2021, 4484 patients with a confirmed diagnosis and patient informed consent have been enrolled from 144 centers across 26 countries. Data from FOS have been published in nearly 60 manuscripts on a wide variety of topics relevant to FD. Analyses of FOS data have investigated the long-term effectiveness and safety of enzyme replacement therapy (ERT) with agalsidase alfa and its effects on morbidity and mortality, as well as the benefits of prompt and early treatment with agalsidase alfa on the progression of cardiomyopathy and the decline in renal function associated with FD. Based on analyses of FOS data, ERT with agalsidase alfa has also been shown to improve additional signs and symptoms of FD experienced by patients. FOS data analyses have provided a better understanding of the natural history of FD and the specific populations of women, children, and the elderly, and have provided practical tools for the study of FD. FOS has also provided methodology and criteria for assessing disease severity which contributed to the continuous development of medical practice in FD and has largely improved our understanding of the challenges and needs of long-term data collection in rare diseases, aiding in future rare disease real-world evidence studies. FOS over the last 20 years has substantially increased the scientific knowledge around improved patient management of FD and continues to expand our understanding of this rare disease.
A Man With Acute Diplopia Francisco, Caiza-Zambrano; Fabio, Maximiliano Gonzalez; Julio, César Galarza ...
Journal of Acute Medicine,
09/2023, Letnik:
13, Številka:
3
Journal Article
Objective
Hereditary myopathy with early respiratory failure (HMERF) is caused by titin A-band mutations in exon 344 and considered quite rare. Respiratory insufficiency is an early symptom. A ...collection of families and patients with muscle disease suggestive of HMERF was clinically and genetically studied.
Methods
Altogether 12 new families with 19 affected patients and diverse nationalities were studied. Most of the patients were investigated using targeted next-generation sequencing; Sanger sequencing was applied in some of the patients and available family members. Histological data and muscle MRI findings were evaluated.
Results
Three families had several family members studied while the rest were single patients. Most patients had distal and proximal muscle weakness together with respiratory insufficiency. Five heterozygous TTN A-band mutations were identified of which two were novel. Also with the novel mutations the muscle pathology and imaging findings were compatible with the previous reports of HMERF.
Conclusions
Our collection of 12 new families expands mutational spectrum with two new mutations identified. HMERF is not that rare and can be found worldwide, but maybe underdiagnosed. Diagnostic process seems to be complex as this study shows with mostly single patients without clear dominant family history.
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