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AIMS: Transthyretin cardiac amyloidosis (ATTR-CA) is a rare and progressive cardiomyopathy caused by amyloid fibril deposition in myocardial tissue. Diagnostic challenges have historically hampered timely detection. Recent advances in noninvasive diagnostic techniques have facilitated ATTR-CA diagnosis. We aimed to examine the development of a regional network for the diagnosis and management of ATTR-CA and describe a cohort of patients with ATTR-CA, investigate diagnostic pathways and assess clinical outcomes according to diagnosis periods. METHODS: We performed a survey study analyzing answers from 11 cardiology centers and we conducted a retrospective study including patients with ATTR-CA attending a referral center between 1 January 2012 and 31 December 2022, and categorized by the period of diagnosis (2012-2016 and 2017-2022). RESULTS: Over the years, a growing number of patients reached a diagnosis and were treated in the surveyed nonreferral centers of the region. The retrospective study showed a more significant diagnostic delay in the earlier period rather than the later one [13.4 (5-30.2) vs. 10.6 (5.0-17.9) months, P = 0.04]. Patients diagnosed after 2017 showed a greater survival rate than those diagnosed earlier ( P = 0.02). In the multivariate analysis, the year of diagnosis from 2017 remained independently associated with mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.28-0.79; P = 0.005]. CONCLUSION: This study emphasized the shift toward noninvasive diagnostic criteria. It revealed a positive impact on patient survival and disease management with the use of disease-modifying therapies and diagnostic developments in more recent years. The findings underscore the importance of disease awareness and networking to reduce diagnostic delays and enhance patient journeys for ATTR-CA.
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Neuropatías Amiloides Familiares , Cardiomiopatías , Diagnóstico Tardío , Derivación y Consulta , Humanos , Estudios Retrospectivos , Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/terapia , Neuropatías Amiloides Familiares/mortalidad , Masculino , Cardiomiopatías/diagnóstico , Cardiomiopatías/terapia , Femenino , Anciano , Derivación y Consulta/estadística & datos numéricos , Factores de Tiempo , Italia , Persona de Mediana Edad , Anciano de 80 o más Años , Encuestas de Atención de la Salud , Tiempo de Tratamiento , Valor Predictivo de las Pruebas , Vías ClínicasRESUMEN
OBJECTIVES: To assess whether COVID-19 could be a concurrent factor in the genesis and/or worsening of stroke and to provide data on COVID-19 -associated stroke patients during the first pandemic wave and comparative data on COVID-19 negative stroke patients in the same period. MATERIALS AND METHODS: This is a retrospective, observational, case-control, single centre study, carried out in a General Hospital in northern Italy. Sixty-three consecutive stroke patients were included, COVID-19-associated stroke was classified as cases and non COVID-19-associated stroke as controls. RESULTS: A total of 19/63 (28.8%) had a COVID-19-associated stroke, 11 /63 (17.5%) were haemorrhagic and 52/63 (82.5%) ischaemic. COVID-19-associated strokes were more severe (p-value 0.019) and had a higher risk of severe disability and/or death (OR 3.79, CI 95%: 1.21-11.93, p-value 0.19). The COVID-19-associated stroke patients with onset during hospitalization for COVID-19 had a more severe stroke than patients with COVID-19 onset during hospitalization for stroke (p-value 0.019). CONCLUSION: Although no relationship was observed between the stroke aetiology and COVID-19, intriguingly, COVID-associated stroke turned out to be more severe and disabling. Hopefully, further studies will provide more data and help in the management of this emerging population.
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COVID-19 , Enfermedades Transmisibles , Accidente Cerebrovascular , Humanos , COVID-19/complicaciones , COVID-19/diagnóstico , SARS-CoV-2 , Estudios de Casos y Controles , Pandemias , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/complicaciones , Estudios Retrospectivos , Enfermedades Transmisibles/complicacionesRESUMEN
Neurofibromatosis type 1 (NF1) is one of the most common genetic tumor predisposition syndrome, caused by mutations in the NF1. To date, few genotype-phenotype correlations have been discerned in NF1, due to a highly variable clinical presentation. We aimed to study the molecular spectrum of NF1 and genotype-phenotype correlations in a monocentric study cohort of 85 NF1 patients (20 relatives, 65 sporadic cases). Clinical data were collected at the time of the mutation analysis and reviewed for accuracy in this investigation. An internal phenotypic categorization was applied. The 94% of the patients enrolled showed a severe phenotype with at least one systemic complication and a wide range of associated malignancies. Spine deformities were the most common complications in this cohort. We also reported 66 different NF1 mutations, of which 7 are novel mutations. Correlation analysis identified a slight significant inverse correlation between age at diagnosis and delayed acquisition of psychomotor skills with residual multi-domain cognitive impairment. Odds ratio with 95% confidence interval showed a higher prevalence of learning disabilities in patients carrying frameshift mutations. Overall, our results aim to offer an interesting contribution to studies on the genotype-phenotype of NF1 and in genetic management and counselling.
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Neurofibromatosis 1 , Genes de Neurofibromatosis 1 , Estudios de Asociación Genética , Humanos , Recurrencia Local de Neoplasia/genética , Neurofibromatosis 1/patología , Neurofibromina 1 , FenotipoRESUMEN
The COVID-19 pandemic poses an ongoing global challenge, and several risk factors make people with multiple sclerosis (pwMS) particularly susceptible to running a severe disease course. Although the literature does report numerous articles on the risk factors for severe COVID-19 and vaccination response in pwMS, there is a scarcity of reviews integrating both these aspects into strategies aimed at minimizing risks. The aim of this review is to describe the risk of vulnerable pwMS exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues related to the SARS-CoV-2 vaccine and to evidence possible future strategies in the clinical management of pwMS. The authors searched for papers on severe COVID-19 risk factors, SARS-CoV-2 vaccination and people with multiple sclerosis in support of this narrative literature review. We propose a multilevel strategy aimed at: the evaluation of risk factors for severe COVID-19 in people with multiple sclerosis, identifying the most appropriate vaccination schedule that is safe for people on disease-modifying drugs (DMDs) and a strict follow-up of high-risk people with multiple sclerosis to allow for the prompt administration of monoclonal antibodies to manage COVID-19 risks in this patient population.
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In the so called COVID19 era, headache, fever and gastrointestinal symptoms are highly suggestive for SARS-CoV-2 infection, but in all the cases presenting to the emergency room, clinicians should always keep in mind alternative diagnoses, particularly if the patient is pregnant. Life-threatening diseases, such as eclampsia and posterior reversible encephalopathy syndrome (PRES), should be promptly recognized and treated. Eclampsia is defined as a seizure occurring in association with pre-eclampsia, and it represents one of the major and serious obstetric disorders associated with significant maternal and perinatal morbidity and mortality. PRES is a distinctive clinical and imaging syndrome characterized by acute headaches, visual impairment, seizures, and altered sensorium, that can be associated with severe eclampsia. Emergency clinicians should always consider eclampsia in the differential diagnosis of headache in pregnant women. The prompt and accurate diagnosis of eclampsia/PRES is crucial to prevent adverse maternal and perinatal outcomes. Here we describe the case of a young pregnant woman admitted to our emergency department for fever, dyspnea, headache, nausea and vomiting, who developed generalized tonic clonic seizures and a subsequent status epilepticus due to eclampsia and PRES.
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COVID-19 , Eclampsia , Síndrome de Leucoencefalopatía Posterior , Eclampsia/diagnóstico , Servicio de Urgencia en Hospital , Femenino , Humanos , Síndrome de Leucoencefalopatía Posterior/diagnóstico por imagen , Síndrome de Leucoencefalopatía Posterior/etiología , Embarazo , SARS-CoV-2RESUMEN
We report the case of a 62-year-old male patient fully vaccinated for COVID-19, admitted to our emergency room for persistent fever associated with exertional dyspnoea, skin lesions, diffuse myalgias and arthralgias not responsive to broad-spectrum antibiotic and antiviral therapy, who developed a rapidly progressive refractory to treatment interstitial lung disease due to anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, that required mechanical ventilation and ECMO. Here, we highlight the importance of always considering alternative diagnoses, i.e. viral and autoimmune diseases, including anti-MDA5 antibody screening, when dealing with patients with a skin rash, seronegative polyarthralgias and interstitial pneumonia, or acute respiratory distress syndrome of unknown origin. LEARNING POINTS: MDA5-associated dermatomyositis is a rare systemic syndrome associated with rapidly progressive and treatment-refractory interstitial lung disease.The anti-MDA5 antibody is the key biomarker for the diagnosis.Early diagnosis is crucial to promptly start aggressive immunosuppressive therapy with the aims of improving prognosis and reducing mortality.
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BACKGROUND: Late Onset Pompe Disease (LOPD) is a rare myopathy characterized by prevailing weakness of trunk and pelvic girdle muscles that causes motor disabilities. Spinal deformities have been reported unclearly on clinical examination. No study quantitatively assessed upright posture defining specific alterations of LOPD various phenotype. OBJECTIVE: Identify postural abnormalities in a homogeneous group of LOPD patients using 3D Stereophotogrammetry (St) and x-Ray (xR). METHODS: Seven LOPD siblings were recruited. They were assessed by clinical scales and, in upright posture, using xR and 3D-St with a new marker set protocol. Fourteen healthy individuals, age and sex-matched, were used as controls for St-parameters; normative xR-values were found in literature. RESULTS: LOPD patients showed a significant weakness of trunk and tibialis anterior muscles. Statistical analysis of St-parameters showed a larger ankle, knee, elbow, dorsal, S2-C7, heel-S2-C7, heel-S2-nasion angles and a lower sagittal vertical axis (SVA) than controls.xR-analysis highlighted an absence of scoliosis and a lower occipito-cervical, C2-C7 cervical and Cobb dorsal angles, and a trend to lower lumbar lordosis and SVA compared to normal values. Significant correlation was found in dorsal and lumbar angles calculated using xR-markers placed on spiny apophysis, xR-centre of vertebral bodies, Cobb-method and St-markers. CONCLUSION: This is the first quantitative study of postural abnormalities in LOPD patients using 3D-St and xR, highlighting sagittal standing alignment changes, difficult to assess to direct exam.Our new St-protocol showed a high reliability compared to xR. Further studies on larger population of LOPD might confirm the usefulness of these instrumental methods for monitoring disease course.
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Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico por imagen , Fotogrametría/métodos , Postura/fisiología , Radiografía/métodos , Posición de Pie , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo II/fisiopatología , Humanos , Lordosis/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Reproducibilidad de los ResultadosRESUMEN
Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype-phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.
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Autofagia/genética , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , alfa-Glucosidasas/genética , Adulto , Anciano , Autofagia/fisiología , Terapia de Reemplazo Enzimático/métodos , Familia , Femenino , Variación Genética/genética , Humanos , Italia , Masculino , Persona de Mediana Edad , Músculo Esquelético/metabolismo , Mutación , Linaje , Músculos Respiratorios , Hermanos , alfa-Glucosidasas/metabolismoRESUMEN
BACKGROUND: Autophagic vacuolar myopathies (AVMs) are an emerging group of heterogeneous myopathies sharing histopathological features on muscle pathology, in which autophagic vacuoles are the pathognomonic morphologic hallmarks. Glycogen storage disease type II (GSDII) caused by lysosomal acid α-glucosidase (GAA) deficiency is the best-characterised AVM. AIMS: This study aimed to investigate the mutational profiling of seven neuromuscular outpatients sharing clinical, myopathological and biochemical findings with AVMs. METHODS: We applied a diagnostic protocol, recently published by our research group for suspected late-onset GSDII (LO-GSDII), including counting PAS-positive lymphocytes on blood smears, dried blood spot (DBS)-GAA, muscle biopsy histological and immunofluorescence studies, GAA activity assay and expression studies on muscle homogenate, GAA sequencing, GAA multiplex ligation-dependent probe amplification (MLPA) and whole exome sequencing (WES). RESULTS: The patients had a limb girdle-like muscular pattern with persistent hyperCKaemia; vacuolated PAS-positive lymphocytes, glycogen accumulation and impaired autophagy at muscle biopsy. Decreased GAA activity was also measured. While GAA sequencing identified no pathogenic mutations, WES approach allowed us to identify for each patient an unexpected mutational pattern in genes cooperating in lysosomal-autophagic machinery, some of which have never been linked to human diseases. CONCLUSIONS: Our data suggest that reduced GAA activity may occur in any condition of impaired autophagy and that WES approach is advisable in all genetically undefined cases of autophagic myopathy. Therefore, deficiency of GAA activity and PAS-positive lymphocytes should be considered as AVM markers together with LC3/p62-positive autophagic vacuoles.
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Autofagia/genética , Genotipo , Enfermedades por Almacenamiento Lisosomal/patología , Enfermedades Musculares/patología , Fenotipo , Autofagia/fisiología , Enfermedad del Almacenamiento de Glucógeno Tipo II/genética , Enfermedad del Almacenamiento de Glucógeno Tipo II/patología , Humanos , Enfermedades por Almacenamiento Lisosomal/genética , Lisosomas/metabolismo , Enfermedades Musculares/genética , Mutación/genética , Secuenciación del Exoma/métodos , alfa-Glucosidasas/genética , alfa-Glucosidasas/metabolismoRESUMEN
BACKGROUND AND PURPOSE: an estimated 40-80% of acute ischemic stroke patients have dysphagia and about 14% develop stroke-associated pneumonia. However, it may be difficult to detect swallowing problems at admission. Moreover, there might not be an on-duty specialist skilled in the diagnosis of this condition. This study aimed at developing a user-friendly bedside examination to identify the risk of dysphagia in stroke patients at hospital admission. METHODS: a diagnostic accuracy study was carried out to assess the concurrent validity of a simple Bedside Screening Tool for Dysphagia (BSTD) in acute stroke. All the consecutive stroke patients admitted between January and April 2018 were enrolled. Sensitivity, specificity, positive (PPV), negative predictive values (NPV) and the Cohen K concordance index scores, reported by nurses and speech-pathologists, were assessed. RESULTS: a total of 67/120 patients (55.8%) were male; overall average age was 67.4 (range 45-91) and 80.8% of the whole population had a history of ischemic stroke. The nursing staff identified 33.3% of dysphagia cases at admission and the speech pathologists 30%. The Cohen K was 0.92 (optimal concordance when K was > 0.8), sensitivity was 100%, specificity 95.2%, PPV 90% and NPV 100%. CONCLUSIONS: our BSTD had a 100% negative predictive value, indicating that this screening test is very useful in ruling out/confirming dysphagia in acute stroke patients.
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Trastornos de Deglución/diagnóstico , Deglución , Pruebas en el Punto de Atención , Accidente Cerebrovascular/complicaciones , Anciano , Anciano de 80 o más Años , Trastornos de Deglución/etiología , Trastornos de Deglución/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatologíaRESUMEN
OBJECTIVE: The dramatic worldwide CoVID-19 infection requires the identification of a reliable and inexpensive tool to quickly discriminate patients with a more unfavorable outcome. METHODS: We performed routine laboratory tests suitable to identify tissue damage and inflammatory status in 123 consecutive CoVID-19 patients admitted to the Emergency Department of the hospital of Piacenza (Emilia-Romagna, Northern Italy). The results were correlated with patients' respiratory function evaluated by the partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2). RESULTS: The most common laboratory abnormalities were lymphocytopenia and elevated values of C-reactive protein (CRP) and lactate dehydrogenase (LDH). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) were also increased. The respiratory performance (PaO2/FiO2) showed a strong inverse correlation with LDH (r = 0.62, r2 0.38, p value < 0.0001) and CRP (r = 0.55, r2 0.31, p value < 0.0001). PaO2/FiO2 values also showed a significant inverse correlation with age (r = -0.37, p < 0.0001), AST (r = -0.31, p < 0.01), WBC (r = -0.49, p < 0.0001), neutrophils count (r = -0.5, p < 0.001). ROC curves showed a sensitivity of 75% and specificity of 70% for the LDH cut-off value of 450 U/L and a sensitivity of 72% and specificity of 71% for the CRP cut-off value of 11 mg/dl in identifying CoVID-19 with moderate-severe ARDS. CONCLUSIONS: LDH and CRP may be related to respiratory function (PaO2/FiO2) and be a predictor of respiratory failure in CoVID-19 patients. LDH and CRP should be considered a useful test for the early identification of patients who require closer respiratory monitoring and more aggressive supportive therapies to avoid poor prognosis.
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Betacoronavirus , Proteína C-Reactiva/metabolismo , Infecciones por Coronavirus/sangre , L-Lactato Deshidrogenasa/sangre , Neumonía Viral/sangre , Insuficiencia Respiratoria/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , COVID-19 , Técnicas de Laboratorio Clínico/métodos , Técnicas de Laboratorio Clínico/tendencias , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Pandemias , Admisión del Paciente/tendencias , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Valor Predictivo de las Pruebas , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/epidemiología , Estudios Retrospectivos , SARS-CoV-2 , Adulto JovenAsunto(s)
Infecciones por Coronavirus , Pandemias , Neumonía Viral , Accidente Cerebrovascular , Betacoronavirus , COVID-19 , Humanos , SARS-CoV-2Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Accidente Cerebrovascular/etiología , Anciano , Anciano de 80 o más Años , COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/terapia , Femenino , Humanos , Italia , Masculino , Pandemias , Neumonía Viral/etiología , Neumonía Viral/terapia , SARS-CoV-2 , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapiaRESUMEN
Dominant Optic Atrophy and Deafness (DOAD) may be associated with one or more of the following disorders such as myopathy, progressive external ophthalmoplegia, peripheral neuropathy, and cerebellar atrophy ("DOA-plus"). Intra- and interfamilial variability of the "DOA-plus" phenotype is frequently observed in the majority of the patients carrying the same mutation in the OPA1 gene. We are describing two familial cases of "DOA-plus" carrying the same c.1334G>A (p.Arg445His) mutation in OPA1 and disclosing different clinical, pathological and biochemical features. The two patients showed different expression levels of the mitochondrial OMI/HTRA2 molecule, which acts as a mitochondrial stress sensor and has been described to interplay with OPA1 in in vitro studies. Our data offer the cue to inquire the role of OMI/HTRA2 as a modifier gene in determining the "DOAplus" phenotype variability.
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Sordera/genética , GTP Fosfohidrolasas/genética , Serina Peptidasa A2 que Requiere Temperaturas Altas/genética , Atrofia Óptica Autosómica Dominante/genética , Adulto , Sordera/fisiopatología , Femenino , Regulación de la Expresión Génica/genética , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Mitocondrias/genética , Mitocondrias/metabolismo , Enfermedades Musculares/genética , Enfermedades Musculares/fisiopatología , Mutación/genética , Oftalmoplejía Externa Progresiva Crónica/genética , Oftalmoplejía Externa Progresiva Crónica/fisiopatología , Atrofia Óptica Autosómica Dominante/fisiopatología , Linaje , Enfermedades del Sistema Nervioso Periférico/genética , Enfermedades del Sistema Nervioso Periférico/fisiopatologíaRESUMEN
Curcumin is a compound isolated from turmeric, a plant known for its medicinal use. Recently, there is a growing interest in the medical community in identifying novel, low-cost, safe molecules that may be used in the treatment of inflammatory and neoplastic diseases. An increasing amount of evidence suggests that curcumin may represent an effective agent in the treatment of several skin conditions. We examined the most relevant in vitro and in vivo studies published to date regarding the use of curcumin in inflammatory, neoplastic, and infectious skin diseases, providing information on its bioavailability and safety profile. Moreover, we performed a computational analysis about curcumin's interaction towards the major enzymatic targets identified in the literature. Our results suggest that curcumin may represent a low-cost, well-tolerated, effective agent in the treatment of skin diseases. However, bypass of limitations of its in vivo use (low oral bioavailability, metabolism) is essential in order to conduct larger clinical trials that could confirm these observations. The possible use of curcumin in combination with traditional drugs and the formulations of novel delivery systems represent a very promising field for future applicative research.
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Curcumina/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Enfermedades de la Piel/tratamiento farmacológico , Piel/efectos de los fármacos , Animales , Curcumina/efectos adversos , Curcumina/farmacocinética , Fármacos Dermatológicos/efectos adversos , Fármacos Dermatológicos/farmacocinética , Humanos , Piel/metabolismo , Piel/patología , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/patología , Resultado del TratamientoRESUMEN
Autophagy is the major intracellular machinery for degrading proteins, lipids, polysaccharides, and organelles. This cellular process is essential for the maintenance of the correct cellular balance in both physiological and stress conditions. Because of its role in maintaining cellular homeostasis, dysregulation of autophagy leads to various disease manifestations, such as inflammation, metabolic alterations, aging, and neurodegeneration. A common feature of many neurologic and neuromuscular diseases is the alteration of the autophagy-lysosomal pathways. For this reason, autophagy is considered a target for the prevention and/or cure of these diseases. Dietary intake of polyphenols has been demonstrated to prevent/ameliorate several of these diseases. Thus, natural products that can modulate the autophagy machinery are considered a promising therapeutic strategy. In particular, curcumin, a phenolic compound widely used as a dietary supplement, exerts an important effect in modulating autophagy. Herein, we report on the current knowledge concerning the role of curcumin in modulating the autophagy machinery in various neurological and neuromuscular diseases as well as its role in restoring the autophagy molecular mechanism in several cell types that have different effects on the progression of neurological and neuromuscular disorders.
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Autofagia/efectos de los fármacos , Curcumina/uso terapéutico , Suplementos Dietéticos , Músculo Esquelético/efectos de los fármacos , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Sistema Nervioso/efectos de los fármacos , Enfermedades Neuromusculares/tratamiento farmacológico , Animales , Proteínas Relacionadas con la Autofagia/metabolismo , Curcumina/efectos adversos , Suplementos Dietéticos/efectos adversos , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Sistema Nervioso/metabolismo , Sistema Nervioso/patología , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades del Sistema Nervioso/patología , Enfermedades Neuromusculares/metabolismo , Enfermedades Neuromusculares/patología , Transducción de SeñalRESUMEN
BACKGROUND: The relative prevalence of myasthenia gravis (MG) subtypes is changing, and their differential features and association with HLA class II alleles are not completely understood. METHODS: Age at onset, presence/absence of autoantibodies (Ab) and thymoma were retrospectively considered in 230 adult Italian patients. Clinical severity, assessed by MGFA scale, and the highest Ab titer were recorded. Furthermore, we performed low/high resolution typing of HLA-DRB1 and HLA-DQB1 alleles to detect associations of these loci with MG subtypes. RESULTS: There were two peaks of incidence: under 41 years of age, with female preponderance, and over 60 years, with higher male prevalence. The former group decreased and the latter increased significantly when comparing onset period 2008-2015 to 2000-2007. Thymomatous (TMG) patients showed a higher prevalence of severe phenotype and significantly higher anti-AChR Ab titer than non-thymomatous (NTMG) patients. Among the latter, those with onset after 60 years of age (LO-NTMG) displayed significantly higher Ab titers but lower MGFA grade compared to early-onset patients (< 41 years; EO-NTMG). Significant associations were found between HLA DQB1*05:01 and TMG patients and between DQB1*05:02 and DRB1*16 alleles and LO-NTMG with anti-AChR Ab. CONCLUSIONS: Two distinct cutoffs (< 41 and > 60 years) conveniently define EO-NTMG and LO-NTMG, with different characteristics. LO-NTMG is the most frequent disease subtype, with an increasing incidence. TMG patients reach higher clinical severity and higher antibody titers than NTMG patients. Moreover, TMG and LO-NTMG with anti-AChR Ab differ in their HLA-DQ association, providing further evidence that these two forms may have different etiologic mechanisms.