BACKGROUND: Left ventricular dysfunction (LVD) is a clinical manifestation of muscular dystrophy (MD) in adults and an important prognostic factor. However, there is a lack of recommendations concerning cardiac followup of these patients. The aim of this work was to evaluate the prevalence of systolic LVD in adults with MD. METHODS: The patients, referred from a Neuromuscular Diseases Unit, underwent clinical evaluation, ECG and transthoracic echocardiogram. Serum troponin I and NT-proBNP were also evaluated. Systolic LVD was defined by an ejection fraction of < .45 and/or shortening fraction of < .25. RESULTS: During a one-year period, we evaluated 24 consecutive patients, 16 men, age 33 +/- 12 years (age at myopathy diagnosis 23 +/- 12 years). They had the following MD: dystrophinopathies--four patients (Duchenne: 1, Becker: 3); Steinert myotonic dystrophy--nine patients; limb-girdle myopathies--six patients; facioscapulohumeral (FSH) myopathies--four patients; and one dysferlinopathy (Miyoshi myopathy). The MD diagnosis, based on clinical and histological criteria, was genetically confirmed in 18 cases (75%). Five patients (20.8%) had thoracic pain, four (16.6%) dyspnea and one a history of syncope. ECG abnormalities were present in 14 cases (58.3%). Stolic LVD or left ventricular remodeling were present in six patients (25%): three with dystrophinopathies, one with limb-girdle myopathy, one with FSH dystrophy and one with myotonic dystrophy. Three patients (12.5%) were diagnosed with heart failure according to the European Society of Cardiology criteria. Three of the five patients with left ventricular dysfunction had elevation of NT-proBNP. One patient with Becker dystrophy had slight elevation of troponin I. In patients with systolic LVD or LV remodeling, the mutations identified were: deletion in intron 1 to exon 49 (one Duchenne MD patient) and deletions in exons 45 to 51 (two Becker MD patients) in the dystrophin gene; deletion of D4Z4 repeats in the DFS locus (4q35)(one patient with FSH MD); and 1300-1500 CTG triplet repeats in the DMPK gene (one patient with myotonic dystrophy). CONCLUSIONS: These results, although preliminary, show that a high percentage of patients with genetically determined skeletal myopathies exhibit cardiac myocyte functional impairment, with severe LVD and heart failure, justifying periodic cardiovascular evaluation. In the future, phenotype-genotype correlations could help to determine the best cardiac surveillance in MD patients.
Other papers by authors:
Elisabete Martins,
Teresa Faria,
J Silva-Cardoso,
Ana Oliveira,
Manuel Campelo,
Sandra Amorim,
Brenda Moura,
F Rocha-Gonçalves,
Jorge G Pereira,
M Júlia Maciel
Faculdade de Medicina do Porto, Serviço de Cardiologia, Hospital de São João, Porto, Portugal. elisabetemartins09@gmail.com
The pathological significance of myocardial adrenergic activity in patients with heart failure is well documented. No previous study has assessed the usefulness of I123-metaiodobenzylguanidine (123I-MIBG) cardiac uptake imaging for the evaluation of familial dilated cardiomyopathy (DCM). OBJECTIVE: To evaluate cardiac adrenergic activity, using 123I-MIBG cardiac uptake imaging, in members of a genotyped family with DCM. METHODS: Clinical evaluation, 12-lead ECG, 2D echocardiogram, heart rate variability analysis by 24h Holter, plasma B-type natriuretic peptide (BNP) measurements and 123I-MIBG cardiac imaging were performed in all participants. Anterior projection planar images and single photon emission computed tomographies of the thorax were obtained 20 min and 4 hours after the intravenous administration of 370 MBq of 123I-MIBG (early and late images). Heart/mediastinal (H/M) ratio and myocardial washout (MW) rate were obtained based on the anterior planar images. In polar maps, segmental uptake of 123I-MIBG was evaluated using a 4-grade visual score: grade 1 - uptake > 75% of maximum myocardial uptake (MMU); grade 2 - uptake 51-75% of MMU; grade 3 - uptake 26-50% of MMU; grade 4 - uptake < or = 25% of MMU. RESULTS: Eleven adults were included: 4 with DCM, 4 with isolated left ventricular enlargement (LVE), and 3 with normal echocardiogram. Patients with DCM and LVE presented higher MW rates, lower H/M ratios and higher visual score grades than those with normal 2D echocardiograms. One patient with a normal echocardiogram but carrying the disease locus also presented an abnormal MIBG cardiac scintigram. CONCLUSION: Patients with the phenotypic expression of the disease (DCM and LVE) and even carriers of the DCM gene with normal echocardiograms may present an abnormal MIBG cardiac scintigram, probably reflecting cardiac adrenergic hyperactivity. If confirmed in larger numbers, this method may be useful for the evaluation of DCM families.
Elisabete Martins,
J Silva-Cardoso,
Cíntia Alves,
Helena Pereira,
Benilde Soares,
Albertino Damasceno,
Cassiano Abreu-Lima,
António Amorim,
F Rocha-Gonçalves
Serviço de Cardiologia do Hospital de São João, Porto, Portugal.
BACKGROUND: It has been estimated that more than 30% of patients with idiopathic dilated cardiomyopathy have a familial form of the disease. The most frequent pattern of inheritance is autosomal dominant and several genes or loci have been implicated, coding for sarcomeric or cytoskeleton proteins. Most of the genotype-phenotype correlations are still under study, but a particular mutation, K210del in the troponin T gene, has been identified in four different families with severe forms of DCM. The pathogenesis of this mutation has been inferred by functional studies but its transmission has not been demonstrated, perhaps due to the high mortality of the affected family members. The aim of this work was to investigate the prevalence of the K210del mutation in Portuguese and Mozambican families with dilated cardiomyopathy. METHODS: We evaluated 27 probands with familial DCM. Forty idiopathic (sporadic) DCM patients and 100 non-related healthy individuals were used as controls. Mutational analysis was performed by amplification of exon 13 of the troponin T gene by the polymerase chain reaction (PCR), determination of molecular weight of PCR products and further sequencing. RESULTS: The K210del mutation in the cardiac troponin T gene was identified in one of the DCM families which presented an aggressive form of the disease, with a high incidence of sudden death, and need for heart transplant at young age. One affected member had sustained left ventricular function recovery after diagnosis. CONCLUSIONS: These results reinforce previous work by others, indicating that this mutation is a bad prognostic factor in familial forms of DCM. The K210del mutation in the troponin T gene, like other mutations in the troponin complex, seems to be especially prevalent in families with rapidly progressive DCM or sudden cardiac death at young age.
Elisabete Martins,
José Silva Cardoso,
Manuel Campelo,
Sandra Amorim,
Brenda Moura,
Maria Júlia Maciel,
Francisco Rocha Gonçalves
Serviço de Cardiologia, Hospital de São João, Porto, Portugal. elisabetemartins09@gmail.com
BACKGROUND: Familial dilated cardiomyopathy (FDCM) is characterized by clinical and genetic heterogeneity. There are still few survival studies concerning this subgroup of patients. AIM: To determine the prognosis of patients with FDCM on optimal medical therapy and attending a heart failure clinic. METHODS: This is a prospective study including patients with FDCM, defined according to the guidelines of the European Society of Cardiology. Cardiovascular morbidity and all-cause mortality were evaluated. RESULTS: Thirty-six patients, 23 (64%) men, were followed for 3.8 +/- 2.5 years. Age at baseline was 42 +/- 14 years and 67% were in NYHA class II. In 22% heart failure symptoms first occurred after a respiratory infection, and in 6%, after pregnancy/delivery. Most patients were in sinus rhythm (89%) and 33% had left bundle branch block (LBBB). Baseline left ventricular (LV) ejection fraction was 28 +/- 9%, LV end-diastolic diameter was 68 +/- 8 mm and left atrial dimension was 46 +/- 9 mm. Baseline serum sodium was 140 +/- 3 mEq/l. All patients were taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs), 81% beta-blockers and 47% spironolactone. During follow-up, 5 patients died, 4 underwent heart transplantation and one received an implantable cardioverter-defibrillator. Five-year survival was 68%. CONCLUSIONS: Five-year survival of our patients with FDCM, under optimal medical therapy, was similar to that of other forms of nonischemic DCM reported in the literature.
Felix Rosumek,
Fernando Silveira,
Frederico de S Neves,
Newton de U Barbosa,
Livia Diniz,
Yumi Oki,
Flavia Pezzini,
G Fernandes,
Tatiana Cornelissen
Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
We reviewed the evidence on the role of ants as plant biotic defenses, by conducting meta-analyses for the effects of experimental removal of ants on plant herbivory and fitness with data pooled from 81 studies. Effects reviewed were plant herbivory, herbivore abundance, hemipteran abundance, predator abundance, plant biomass and reproduction in studies where ants were experimentally removed (n = 273 independent comparisons). Ant removal exhibited strong effects on herbivory rates, as plants without ants suffered almost twice as much damage and exhibited 50% more herbivores than plants with ants. Ants also influenced several parameters of plant fitness, as plants without ants suffered a reduction in biomass (-23.7%), leaf production (-51.8%), and reproduction (-24.3%). Effects were much stronger in tropical regions compared to temperate ones. Tropical plants suffered almost threefold higher herbivore damage than plants from temperate regions and exhibited three times more herbivores. Ant removal in tropical plants resulted in a decrease in plant fitness of about 59%, whereas in temperate plants this reduction was not statistically significant. Ant removal effects were also more important in obligate ant-plants (=myrmecophytes) compared to plants exhibiting facultative relationships with hemiptera or those plants with extrafloral nectaries and food bodies. When only tropical plants were considered and the strength of the association between ants and plants taken into account, plants with obligate association with ants exhibited almost four times higher herbivory compared to plants with facultative associations with ants, but similar reductions in plant reproduction. The removal of a single ant species increased plant herbivory by almost three times compared to the removal of several ant species. Altogether, these results suggest that ants do act as plant biotic defenses, but the effects of their presence are more pronounced in tropical systems, especially in myrmecophytic plants.
Elisabete Martins,
José Silva-Cardoso,
Manuel Bicho,
Mafalda Bourbon,
Fátima Ceia,
M José Rebocho,
Brenda Moura,
Cândida Fonseca,
Maria José Correia,
Dulce Brito,
Carlos Perdigão,
Hugo Madeira,
Cassiano Abreu-Lima
Serviço de Cardiologia-Hospital de São João, Faculdade de Medicina do Porto, Porto, Portugal. bernardes_med@hotmail.com
Dilated cardiomyopathy (DCM) is a myocardial disease, characterized by ventricular dilatation and impaired systolic function, that in more than 30% of cases has a familial or genetic origin. Given its age-dependent penetrance, DCM frequently manifests in adults by signs or symptoms of heart failure, arrhythmias or sudden death. The predominant mode of inheritance is autosomal dominant, and in these cases mutations are identified in genes coding for cytoskeletal, sarcomeric or nuclear envelope proteins. To date, most studies aimed at molecular diagnosis of DCM have been in selected families, or in larger groups of patients, but screening for mutations in a limited number of genes. Consequently, the epidemiology of mutations in familial DCM remains unknown. There is thus a need for multicenter studies, involving screening for a wide range of mutations in several families and in cases of idiopathic DCM. The present article describes the methodology of a multicenter study, aimed at clinical and molecular characterization of familial DCM patients in the Portuguese population.
Fernando Silveira,
Ralph Lainson,
Elza Pereira,
Adelson de Souza,
Marliane Campos,
Eugênia Chagas,
Claudia Gomes,
Márcia Laurenti,
Carlos Corbett
Parasitology Department, Evandro Chagas Institute (Surveillance Secretary of Health, Ministry of Health), Av. Almirante Barroso, 492, 66090-000, Belém, Pará State, Brazil, silveiraft@lim50.fm.usp.br.
This was a longitudinal study carried out during a period over 2 years with a cohort of 946 individuals of both sexes, aged 1 year and older, from an endemic area of American visceral leishmaniasis (AVL) in Pará State, Brazil. The object was to analyze the transmission dynamics of human Leishmania (Leishmania) infantum chagasi infection based principally on the prevalence and incidence. For diagnosis of the infection, the indirect fluorescent antibody test (IFAT) and leishmanin skin test (LST) were performed with amastigote and promastigote antigens of the parasite, respectively. The prevalence by LST (11.2%) was higher (p < .0001) than that (3.4%) by IFAT, and the combined prevalence by both tests was 12.6%. The incidences by LST were also higher (p < .05) than those by IFAT at 6 (4.7% x .6%), 12 (4.7% x 2.7%), and 24 months (2.9% x .3%). Moreover, there were no differences (p > .05) between the combined incidences by both tests on the same point surveys, 5.2%, 6.3%, and 3.6%. During the study, 12 infected persons showed high IFAT IgG titers with no LST reactions: five children and two adults developed AVL (2,560-10,120), and two children and three adults developed subclinical oligosymptomatic infection (1,280-2,560). The combined tests diagnosed a total of 231 cases of infection leading to an accumulated prevalence of 24.4%.
Department of Neurology, Hospital de São João, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal. jmassano@med.up.pt
Marliane Campos,
Cláudia De Castro Gomes,
Adelson de Souza,
Ralph Lainson,
Carlos Corbett,
Fernando Silveira
Evandro Chagas Institute (Surveillance Secretary of Health, Ministry of Health), Belém, Pará State, Brazil, marlianecampos@iec.pa.gov.br.
There is little available information regarding the infectivity of New World Leishmania species, particularly those from the Amazonian Brazil, where there are six species of the subgenus Viannia causing American cutaneous leishmaniasis (ACL). The aim of this study was to compare, in vitro, the potential infectivity of the following Leishmania (Viannia) spp.: L.(V.) braziliensis from localized cutaneous leishmaniasis (LCL) and mucocutaneous leishmaniasis (MCL) patients, L.(V.) guyanensis, L.(V.) shawi, L.(V.) lainsoni and L.(V.) naiffi from LCL patients only, in cultured BALB/c mice peritoneal macrophage, as well as the production of NO by the infected cells. The infectivity of parasites was expressed by the infection index and, the nitric oxide (NO) production in the macrophage culture supernatant was measured by the Griess method. It was found that L.(V.) braziliensis from MCL, the more severe form of disease, showed the highest (p </= .05) infection index (397), as well as the lowest NO production (2.15 muM) compared with those of other species. In contrast, L.(V.) naiffi which is less pathogenic for the human showed the lowest infection index (301) and the highest NO production (4.11 muM). These results demonstrated a negative correlation between the infectivity and the ability of these parasites to escape from the microbicidal activity of the host cell.
Serviços de Neurologia e de Neurofisiolgia, Hospital de São João, Porto.
Peripheral neuropathy is a general term for peripheral nerve disease. The impairment of peripheral nerve is a very frequent situation with a limited clinical expression, but with several subjacent etiologies. Therefore in clinical practice more complicated than identify a neuropathy is the work-up of its etiological study. The clinical investigation and electrophysiologic study are fundamental in the investigation study of a neuropathy. The authors present a schematic revision work of the principals aspects of neuropathy clinical and study.
Ana Azevedo,
Paulo Bettencourt,
Margarida Alvelos,
Elisabete Martins,
Cassiano Abreu-Lima,
Hans-Werner Hense,
Henrique Barros
BACKGROUND: To estimate the impact on quality of life of evolving stages of heart failure in a community sample of Portuguese adults. METHODS: Cross-sectional evaluation of 424 adults aged >/=45 years. Subjects were classified in stages defined by the American College of Cardiology: low risk, high risk for heart failure (stage A), asymptomatic cardiac dysfunction (stage B), symptomatic heart failure (stage C). Quality of life was assessed using 8 sub-domains of Short Form 36: physical functioning, role limitations-physical problems, bodily pain, general health perception, social functioning, vitality, role limitations-emotional problems and mental health. RESULTS: Women scored significantly lower on all sub-domains. Quality of life decreased with age and increased with socioeconomic status. Adjusting for gender, age and education, physical sub-domains, general health perception, social functioning and role limitations-emotional problems decreased significantly with increasingly severe heart failure stages in women and men. No significant association was found with vitality and mental health. CONCLUSION: Significantly lower scores on quality of life sub-domains were found across increasing severity of heart failure stages, even in the early asymptomatic phases. The results contradict conceptual frameworks which suggest that the impact of heart failure on quality of life depends on symptoms.
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Service de Neurologie inflammatoire et infectieuse, Hôpital Roger Salengro, CHRU Lille, France. helenebourteel@yahoo.fr
BACKGROUND: Limb-girdle muscular dystrophy 2I (LGMD2I) is caused by mutations in the fukutin-related protein gene FKRP, which is also involved in congenital muscular dystrophy (MDC1C). OBJECTIVE: To evaluate the clinical, biological, radiological and mutational characteristics of LGMD2I patients with FKRP mutation. METHODS: Eleven patients from nine families from the north of France were studied. Demographical data, muscular testing results, cardiac and respiratory examinations, muscle histological features and a genetic analysis of the FKRP gene for each patient are reported. Eight patients underwent brain MRI and seven neuropsychological tests. RESULTS: The patients included six women and five men. The mean age at onset was 9 years (range 1.5 to 23 years). Five patients remained self-ambulatory, whereas the other six were confined to a wheelchair by a mean age of 19 years, after a mean disease duration of 10 years. Nine patients suffered from restrictive respiratory insufficiency, and two male patients had severe dilated cardiomyopathy. Neuropsychological tests revealed memory impairment in four cases. Brain MRI revealed cerebral abnormalities in four patients (4/8). Ten patients were carriers of the common L276I mutation, which was either homozygous (four patients) or heteroallelic with another mutation (six patients). Among the mutations found, three were novel: L322V, L489R and R275G. CONCLUSIONS: This study reveals inter- and intrafamilial phenotypic variability in LGMD2I, with a preponderance of myocardiopathy and restrictive respiratory insufficiency. It also demonstrates central nervous involvement, probably associated with changes in alpha-dystroglycan expression in the brain.
1Department of Cardiology, Zentralklinik Bad Berka, Robert-Koch-Allee 9, 99437 Bad Berka, Germany.
Aims Congenital left ventricular aneurysm (LVA) and diverticulum (LVD) are rare cardiac anomalies and can be associated with ECG abnormalities and rhythm disturbances. We sought to investigate the prevalence and the spectrum of ECG abnormalities in such patients. Methods and results We assessed 125 patients with isolated LVA or LVD for the prevalence of ECG abnormalities and compared the findings to an age- and gender-matched control group. The 12-lead ECG patterns were evaluated according to commonly used criteria and were classified into three subgroups (distinct, mildly, and minor). Fifty-four of the 125 patients (43.2%) had normal and 71 (56.8%) abnormal ECGs. Mean age was 66 years. Forty-nine (39.2%) were male. Distinct abnormal ECG patterns were more prevalent in patients with LVD (38.2 vs. 15.8%, P = .04), and apical location of the anomaly (36.6 vs. 16.6%, P = .02). Older age (>66 years) was associated with a trend for a higher prevalence of abnormal ECG pattern (33 vs. 18%, P = .06), whereas gender had no influence (32 vs. 16%, P = .14). This study also shows that the sensitivity, specificity, positive predictive value and negative predictive value of a 12-lead ECG for the diagnosis of LVA or LVD are low. Conclusion This large single-centre study suggests that the prevalence of abnormal ECG patterns in patients with isolated LVA or LVD is as high as 56.8%. However, ECG is not specific and sensitive to be used as a screening tool in such patients.
Prevalence of duchenne/becker muscular dystrophy among males aged 5--24 years --- four States, 2007.
Muscular dystrophies are a group of genetic diseases characterized by progressive skeletal muscle weakness and muscle cell death with replacement of muscle cells by fibrosis and fat. The most common muscular dystrophy in children is Duchenne muscular dystrophy (DMD), which predominantly affects males. Historically, DMD has resulted in loss of ambulation between ages 7 and 13 years and death in the teens or 20s. The average age at diagnosis is 5 years, despite earlier onset of symptoms. Becker muscular dystrophy is similar to DMD but has later onset and slower, more variable progression of symptoms. Birth prevalence of DMD has been estimated at 1 in 3,500 (2.9 per 10,000) male births and Becker muscular dystrophy at 1 in 18,518 ( .5 per 10,000) male births. To estimate the population-based prevalence of Duchenne/Becker muscular dystrophy (DBMD) and describe selected clinical outcomes, CDC and investigators from the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) analyzed data for males born during 1983--2002 that were reported to the MD STARnet from four participating states. This report summarizes those findings, which indicated overall state-specific prevalences on January 1, 2007, of 1.3--1.8 per 10,000 males aged 5--24 years. Among MD STARnet subjects, more than 90% of males with DBMD aged >/=15 years used wheelchairs. Nearly 60%percnt; of males with DBMD born during 1983--1987 had survived through 2007, emphasizing the need to develop and implement programs that address lifelong needs of males with DBMD.
Division of Cardiology, Robert-Bosch-Krankenhaus, Stuttgart, Germany.
Cardiac involvement in patients with a sarcoglycanopathy (limb-girdle muscular dystrophy) has been described previously; however, this is the first cardiovascular magnetic resonance (CMR) study in such a patient demonstrating an interesting pattern of myocardial damage using late gadolinium enhancement (LGE) imaging. Moreover, the wall motion abnormality and the subepicardial pattern of LGE in this patient with a sarcoglycanopathy is in agreement with the findings in another patient with Becker muscular dystrophy. The predominance of LGE in the subepicardial layers of the left ventricular inferolateral wall suggests that such a myocardial damage pattern represents a nonspecific cardiac phenotype in response to exaggerated mechanical stress in this region, at least in patients with a sarcoglycanopathy or dystrophinopathy. J. Magn. Reson. Imaging 2009;30:876-877.(c) 2009 Wiley-Liss, Inc.
Cardiac Unit, Kantonsspital St. Gallen, Switzerland. roman.brenner@kssg.ch
A 19-year-old man suffered a cardiac arrest during a promenade with his friends. Cardiac resuscitation was started immediately. Anamnesis uncovered that the father as well as a cousin of the patient suffered from myotonic dystrophy (MD). Follow-up ECG monitoring showed intercurrent III degree AV-block as well as several asymptomatic episodes of ventricular tachycardias, atrial flutter with changing conduction and atrial fibrillation. Neuromuscular testing and genetic analyses confirmed the diagnosis of a myotonic dystrophy. Myotonic dystrophy (MD) is a chronic, slowly progressing, autosomal dominant inherited multisystemic disease.The clinical presentation is characterized by wasting of the muscles with delayed relaxation, cataracts and endocrine changes. MD is associated with both cardiac conduction disturbances and structural heart abnormalities. Electrocardiographic abnormalities include conduction disturbances or tachyarrhythmias. This case illustrates that potentially lethal arrhythmias inducing sudden cardiac death may occur in MD patients even in the absence of neurologic symptoms characterizing the systemic illness.
Department of Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Only sparse information is available concerning the relationship between pregnancy and hereditary neuromuscular disorders. This review deals with several issues like the effects of such conditions on female fertility (myotonic dystrophy type 1 and mitochondrial disorders), on the risk to the fetus (myotonic dystrophy type 1 and Charcot-Marie-Tooth disease), on the ability to carry pregnancy and its complications (markedly increased preterm labor in myotonic dystrophies and spinal muscular atrophy), on the labor and its possible need for interventions (myotonic dystrophy type 1, facioscapulohumeral dystrophy and Charcot-Marie-Tooth disease). It also discusses the question of pregnancy effects on the course of the inherited neuromuscular disorders (myotonic dystrophies, spinal muscular atrophy, facioscapulohumeral dystrophy, Charcot-Marie-Tooth disease, congenital myopathy and limb-girdle muscular dystrophy). The aim of this critical review is to point at pregnancy-related problems that need further research.
Department of Physical Therapy, College of Health Science, Kaohsiung Medical University, and Department of Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Muscular dystrophy (MD) comprises a group of diseases characterized by progressive muscle weakness that induces functional deterioration. Clinical management requires the use of a well-designed scale to measure patients' functional status. This study aimed to investigate the quality of the functional scales used to assess patients with different types of MD. The Brooke scale and the Vignos scale were used to grade arm and leg function, respectively. The Barthel Index was used to evaluate the function of daily living activity. We performed tests to assess the acceptability of these scales. The characteristics of the different types of MD are discussed. This was a multicenter study and included patients diagnosed with Duchenne muscular dystrophy (DMD)(classified as severely progressive MD), Becker muscular dystrophy (BMD), limb girdle muscular dystrophy (LGMD) and facioscapulohumeral muscular dystrophy (FSHD). BMD, LGMD, and FSHD were classified as slowly progressive MD. The results demonstrated that the Brooke scale was acceptable for grading arm function in DMD, but was unable to discriminate between differing levels of severity in slowly progressive MD. The floor effect was large for all types of slowly progressive MD (range, 20. -61.9), and was especially high for BMD. The floor effect was also large for BMD (23.8%) and FSHD (50. %) using the Vignos scale. Grades 6-8 of the Vignos scale were inapplicable because they included items involving the use of long leg braces for walking or standing, and some patients did not use long leg braces. In the Barthel Index, a ceiling effect was prominent for slowly progressive MD (58.9%), while a floor effect existed for DMD (17.9%). Among the slowly progressive MDs, FSHD patients had the best level of functioning; they had better leg function and their daily living activities were less affected than patients with other forms of slowly progressive MD. The results of this study demonstrate the acceptability of the different applications used for measuring functional status in patients with different types of MD. Some of the limitations of these measures as applied to MD should be carefully considered, especially in patients with slowly progressive MD. We suggest that these applications be used in combination with other measures, or that a complicated instrument capable of evaluating the various levels of functional status be used.
Unité de Neuropédiatrie, Hôpital Necker, Paris cedex 15, France. isabelle.desguerre@nck.aphp.fr
The Ohio State University College of Nursing, Columbus, Ohio, USA.
PURPOSE: To review the current understanding of the pathophysiology of dilated cardiomyopathy (DCM) in patients with Duchenne and Becker muscular dystrophies, assessment of cardiac dysfunction for these patients, and the recommended pharmacological treatment options and ongoing research directions. DATA SOURCES: Reviews and original research articles from scholarly journals and books. CONCLUSIONS: Duchenne and Becker muscular dystrophies are debilitating neuromuscular disorders, both caused by mutations in the dystrophin gene. Most patients develop DCM as part of the disease course; in fact, DCM is the leading cause of death among these patients. Cardiac surveillance, including routine monitoring of electrocardiograms, echocardiograms, and appropriate blood biomarkers, may detect early DCM development. Although previous studies have shown that early administration of cardiac medications may delay the development of DCM, current standard of care does not emphasize cardiac surveillance and timely treatment. This, in turn, limits clinicians, including advanced practice nurses, to be optimally engaged in providing the most aggressive and proactive patient care. IMPLICATIONS FOR PRACTICE: Implementing a routine cardiac assessment and timely pharmacological treatment in primary or specialty care settings is highlighted as an important step to optimize cardiac health among patients with Duchenne and Becker muscular dystrophies.
Emma Ciafaloni,
Deborah J Fox,
Shree Pandya,
Christina P Westfield,
Soman Puzhankara,
Paul A Romitti,
Katherine D Mathews,
Timothy M Miller,
Dennis J Matthews,
Lisa A Miller,
Christopher Cunniff,
Charlotte M Druschel,
Richard T Moxley
Department of Neurology (E.C., S.P., R.M.), University of Rochester, Rochester, NY; New York State Department of Health (D.F., C.W., C.D.), Troy, NY; Department of Epidemiology (S.P., P.R.), University of Iowa, College of Public Health, Iowa City, IA; Department of Pediatrics (K.M.), University of Iowa Carver College of Medicine, Iowa City, IA; The Departments of Pediatrics and Neurology and the Steele Children's Research Center (T.M., C.C.), University of Arizona College of Medicine, Tucson, AZ; Department of Physical Medicine and Rehabilitation (D.M.), University of Colorado School of Medicine, The Children's Hospital, Denver, CO; and Colorado Department of Public Health and Environment (L.M.), Denver, CO.
OBJECTIVE: To identify key factors for the delay in diagnosis of Duchenne muscular dystrophy (DMD) without known family history. STUDY DESIGN: The cohort comes from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), a multistate, multiple-source, population-based surveillance system that identifies and gathers information on all cases of Duchenne and Becker muscular dystrophy born since 1982. We analyzed medical records of 453 Duchenne and Becker muscular dystrophy boys to document the time course and steps taken to reach a definitive diagnosis. RESULTS: Among 156 boys without known family history of DMD prior to birth, first signs or symptoms were noted at a mean age of 2.5 years. Concerns resulted in primary care provider evaluation of the child at a mean age of 3.6 years. Mean age at time of initial creatine kinase was 4.7 years. Mean age at definitive diagnosis of DMD was 4.9 years. CONCLUSIONS: There is a delay of about 2.5 years between onset of DMD symptoms and the time of definitive diagnosis, unchanged over the previous 2 decades. This delay results in lost opportunities for timely genetic counseling and initiation of corticosteroid treatment. We recommend checking creatine kinase early in the evaluation of boys with unexplained developmental delay.