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INTRODUCTION/AIMS: The common presentations of statin intolerance are muscle-specific symptoms. Although statins are one type of drug reported to cause myasthenic worsening, myasthenic worsening has not been recognized as statin intolerance. The purpose of the present study is to investigate in a large cohort the safety profiles of statins in patients with myasthenia gravis (MG). METHODS: A total of 1710 consecutive patients with MG who visited sites associated with the Japan MG registry 2021 group between April and October 2021 were reviewed. Statin-associated myasthenic worsening was defined as worsening of any myasthenic symptoms on statin use and improvement of the symptom by stopping the statin or by undertaking additional treatment with patient and doctor confirmation. RESULTS: Among the 400 patients who used statins, 8 (2%) patients experienced statin intolerance and 6 (1.5%) patients experienced myasthenic worsening. No patients developed MG on the statin. Ptosis was a main symptom of myasthenic worsening in 4 (67%) patients. Atorvastatin was used in all patients with statin-associated myasthenic worsening. The symptoms of statin intolerance and statin-associated myasthenic worsening were improved within 2 months and 3 months, respectively, in all patients by cessation of statin use. DISCUSSION: Regarding statin-associated myasthenic worsening, prevalence was low, and severity was mild; with cessation of statin use, symptoms improved within a few months, and outcomes were generally good. Although statins can be used in MG patients with little concern, statin-associated myasthenic worsening should be noted in addition to the classical statin intolerance associated with statin use.
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Since one of the main characters in Three Act Tragedy was an actor, the three murders described in the book have been likened to a curtain. The three seemingly unrelated murders were connected at the end of the story, a thrill unique to the author, Agatha Christie. Nicotine was used in all three murders in this book. Nicotine is highly toxic and was one of the main pesticides used until the mid-20th century. Although its use is currently prohibited, neonicotinoid pesticides, which have reduced toxicity, are still being used. Problems with nicotine intoxication include accidental ingestion by young children, green tobacco sickness, and suicide attempts. When nicotine enters the body, it binds to acetylcholine receptors and causes various symptoms.
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Nicotina , Plaguicidas , Humanos , Nicotina/metabolismo , Nicotina/envenenamiento , Plaguicidas/metabolismo , Plaguicidas/envenenamiento , Obras de Ficción como AsuntoRESUMEN
Dystonia is a movement disorder characterized by sustained muscle contractions that result in abnormal "patterned" movements and/or postural abnormalities. Based on the accompanying symptoms, dystonia can be classified as isolated (i.e., with dystonia only), combined (i.e., with other movement disorders such as myoclonus), or complex (i.e., with symptoms other than movement disorders such as mental retardation). Moreover, dystonia may affect single or multiple parts of the body and accordingly be classified as focal, segmental, multifocal, hemi, or generalized. The most common type of dystonia is isolated focal dystonia, often accompanied with a specific action (task-specific action). The "task-specificity" uniquely illustrates the nature of dystonia, and this phenomenon is most clearly observed in occupation-related dystonias that include musician's and athlete's dystonia. In this article, we first elucidate the general issues of common focal dystonia (cervical dystonia, blepharospasm, and focal hand dystonia) and then present several educational cases of occupational (task-specific) dystonia with some clinical pearls for practical management.
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Distonía , Trastornos Distónicos , Trastornos del Movimiento , Humanos , Distonía/diagnóstico , Trastornos Distónicos/diagnóstico , MovimientoRESUMEN
Lorenzo's Oil, an American movie released in 1992, is based on a true story of a couple who spare no effort to search for a cure for their 5-year-old son who gradually develops eccentricities and signs of progressive motor and speech disturbances and is diagnosed with adrenoleukodystrophy. Despite lack of medical knowledge, Lorenzo's parents embark on a mission to study the disease on their own and eventually discover a therapeutic mixture referred to as Lorenzo's oil. Most characters in the movie retained real-life names. Even after its release in 1992, the movie has provided some subjects in many ways.
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Adrenoleucodistrofia , Ácidos Erucicos , Humanos , Preescolar , Ácidos Erucicos/uso terapéutico , Trioleína/uso terapéutico , Adrenoleucodistrofia/tratamiento farmacológico , Combinación de MedicamentosRESUMEN
Associated factors of the Myasthenia Gravis Activities of Daily Living (MG-ADL) score were investigated in 55 patients who had had generalized MG for more than 5 years. In multivariate analysis, correlates of the MG-ADL score at the last follow-up were the total number of fast-acting treatments (FTs) (standardized regression coefficient 0.617ï¼P < 0.001) and Myasthenia Gravis Foundation of America (MGFA) classification (standardized regression coefficient 0.227ï¼P = 0.032) (F = 32.7ï¼P < 0.001). In patients with a score of 5 or more on MG-ADL at the last follow-up, tendency as follows were seen: 1) early-onset (P = 0.002), 2) longer duration (P = 0.014), 3) high frequency of MGFA classification V (P = 0.017), 4) high frequency of the total number of FTs (P < 0.001), and 5) higher dose of prednisolone at the last follow-up (P = 0.003). MGFA V, early-onset without depending on E-L-T classification, or difficulty of reduction for high doses of prednisolone can be the target of novel treatment for MG, and future prospective study will be expected.
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Actividades Cotidianas , Miastenia Gravis , Humanos , Estudios Prospectivos , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamiento farmacológico , Prednisolona , PacientesRESUMEN
For essential tremors that are refractory to standard medical treatment, surgical treatment is considered when there is obstruction in activities of daily living. However, there are patients who do not wish to undergo or are contraindicated for surgical treatment. In this paper, we explored what is considered to be the standard medical treatment and when surgery cannot be performed. In Japan, medical treatment is based on the use of arotinolol and primidone, and combination therapy and second-line drugs are extensively discussed. Furthermore, an algorithm of the treatment for essential tremors in Japan has been provided.
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Temblor Esencial , Actividades Cotidianas , Temblor Esencial/tratamiento farmacológico , Temblor Esencial/cirugía , Humanos , Japón , Primidona/uso terapéuticoRESUMEN
A 36-year-old man experienced severely impaired consciousness twice after drinking because of hyperammonemia. No abnormal blood tests were found other than ammonia levels. However, magnetic resonance imaging (MRI) showed atrophy of the brain parenchyma. One the second occasion, the patient suffered severe impairment of consciousness, and because of seizures and glossoptosis, mechanical ventilation was started. Urea cycle disorders (UCDs) were assumed to be involved. Genetic testing revealed a monoallelic mutation of the carbamoyl phosphate synthase 1 (CPS1) gene. When transient hyperammonemia of unknown cause occurs repeatedly in adults, an active investigation for UCDs should be conducted.
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Enfermedad por Deficiencia de Carbamoil-Fosfato Sintasa I , Hiperamonemia , Trastornos Innatos del Ciclo de la Urea , Adulto , Carbamoil-Fosfato Sintasa (Amoniaco)/genética , Enfermedad por Deficiencia de Carbamoil-Fosfato Sintasa I/complicaciones , Enfermedad por Deficiencia de Carbamoil-Fosfato Sintasa I/genética , Carbamoil Fosfato , Estado de Conciencia , Humanos , Hiperamonemia/complicaciones , Hiperamonemia/diagnóstico , Hiperamonemia/genética , Masculino , Mutación/genética , Trastornos Innatos del Ciclo de la Urea/complicacionesRESUMEN
A 62-year-old female patient with systemic lupus erythematosus (SLE) was admitted for cerebral infarction. The magnetic resonance angiography showed focal narrowing of the cerebral arteries that was initially considered as atherosclerosis due to her cardiovascular risk factors. Ten weeks later, she was again admitted for multiple cerebral infarctions. Vessel wall magnetic resonance imaging revealed gadolinium enhancement of the arterial walls of the narrowing lesions, leading to a diagnosis of cerebral arteritis. Based on a literature review, cerebral medium-sized arteritis in SLE likely progresses insidiously during the active phase of SLE, which may later result in occlusion irrespective of disease activity.
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Arteritis , Infarto Cerebral , Ciclofosfamida/uso terapéutico , Lupus Eritematoso Sistémico , Vasculitis por Lupus del Sistema Nervioso Central , Angiografía por Resonancia Magnética/métodos , Paresia , Antirreumáticos/uso terapéutico , Arteritis/diagnóstico por imagen , Arteritis/etiología , Infarto Cerebral/diagnóstico , Infarto Cerebral/etiología , Infarto Cerebral/fisiopatología , Infarto Cerebral/terapia , Imagen de Difusión por Resonancia Magnética/métodos , Progresión de la Enfermedad , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/terapia , Vasculitis por Lupus del Sistema Nervioso Central/complicaciones , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Persona de Mediana Edad , Paresia/diagnóstico , Paresia/etiología , Paresia/terapia , Gravedad del Paciente , Pronóstico , RecurrenciaRESUMEN
Sjögren syndrome (SS) is one of several collagen vascular diseases that occasionally involve the central nervous system. We report two cases of SS involving young patients who initially presented with aseptic meningitis. A male with recurrent AM was found to have anti-Ro/SSA and La/SSB antibodies in a screening test for autoimmune process. A minor salivary gland biopsy revealed lymphocytic infiltrations compatible with SS, although the patient did not exhibit sicca symptoms. A female presenting with AM and polyarthritis also reported xerophthalmia. Anti-Ro/SSA antibody testing and a positive result in a minor salivary gland biopsy led to the diagnosis of SS. In the literature review, we found that AM or aseptic meningoencephalitis (AME) preceded or had a concomitant onset with SS in approximately 70% of cases. Screening for anti-Ro/SSA antibody, as well as systemic assessment for rheumatic symptoms, may be useful for diagnosing AM/AME of unknown etiology.
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Meningitis Aséptica/diagnóstico por imagen , Meningitis Aséptica/diagnóstico , Síndrome de Sjögren/diagnóstico por imagen , Síndrome de Sjögren/diagnóstico , Adulto , Humanos , Imagen por Resonancia Magnética , Masculino , Meningoencefalitis/diagnóstico , Meningoencefalitis/diagnóstico por imagen , Adulto JovenRESUMEN
Differentiating Parkinson's disease (PD) from multiple system atrophy with predominant parkinsonism (MSA-P) or progressive supranuclear palsy-parkinsonism (PSP-P) in early stages of the disease is extremely difficult. MSA-P and PSP-P are often misdiagnosed as PD. MSA-P and PSP-P may be diagnosed in their early stages by considering clinical symptoms and neuroradiological findings together. Diffusion weighted images, T2* weighted images and proton density weighted images are useful for diagnosis MSA-P in early stages , while the magnetic resonance parkinsonism index is useful tool for diagnosis of PSP-P in the early stage.
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Atrofia de Múltiples Sistemas/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Parálisis Supranuclear Progresiva/diagnóstico por imagen , Diagnóstico Diferencial , Humanos , Imagen por Resonancia MagnéticaRESUMEN
INTRODUCTION: In myasthenia gravis (MG) patients on intravenous methylprednisolone (IVMP) therapy, initial deterioration should be carefully monitored because it may cause myasthenic crisis. The aim of this study was to investigate the onset, duration and related factors of initial deterioration from the first IVMP in MG patients. METHODS: A total dose of IVMP in the first cycle of 750 mg or less, over 750 to 1500 mg, and over 1500 to 3000 mg was used in the analysis. Initial deterioration was evaluated in qualitative and quantitative evaluation and was defined as an increase of 2 or more points on the The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale after the start of IVMP therapy in the quantitative evaluation. RESULTS: We enrolled 51 mainly mild MG patients. The mode of onset of initial deterioration from the first IVMP treatment was day 4 in the qualitative and quantitative evaluation. In addition, the mode of duration was 3 days. In multiple logistic regression analysis, factors related to initial deterioration were MGFA classification with overall disease duration up to just before IVMP and thymectomy before IVMP in both the qualitative and the quantitative evaluation (p < .001). One to four cycles of IVMP improved the MG-ADL score at hospital discharge from that at the start of IVMP (p < .001). CONCLUSION: Disease severity and thymectomy before IVMP are related to initial deterioration in MG patients. IVMP can be repeated after initial deterioration weekly in most patients.
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Metilprednisolona , Miastenia Gravis , Actividades Cotidianas , Humanos , Miastenia Gravis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Timectomía , Resultado del TratamientoRESUMEN
BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in GLA, which encodes the enzyme α-galactosidase A (α-Gal A). Although the prevalence of Fabry disease in patients with stroke has been reported to range from 0% to 4%, few cohort studies have examined Japanese stroke patients. We aimed to clarify the prevalence of Fabry disease and the frequency of GLA mutations among patients with young-onset stroke in Japan. METHODS: From April 2015 to December 2016, we enrolled patients with young-onset (≤60 years old) ischemic stroke or intracerebral hemorrhage. We measured α-Gal A activity and the concentration of globotriaosylsphingosine in plasma. Genetic evaluations were performed in patients with low α-Gal A activity or high concentrations of globotriaosylsphingosine. RESULTS: Overall, 516 patients (median age of onset, 52 years old; 120 women) were consecutively enrolled in this study. Five patients (4 men and 1 woman) had low α-Gal A activity, and no patients were detected with the screen for plasma globotriaosylsphingosine levels. The genetic analysis did not identify a causative mutation responsible for classic Fabry disease in any of the patients, but 2 patients (.4%) carried the p.E66Q in GLA. CONCLUSIONS: No patient with Fabry disease was detected in our young-onset stroke cohort.
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Isquemia Encefálica/sangre , Hemorragia Cerebral/sangre , Enfermedad de Fabry/sangre , Glucolípidos/sangre , Esfingolípidos/sangre , Accidente Cerebrovascular/sangre , alfa-Galactosidasa/sangre , Adulto , Edad de Inicio , Isquemia Encefálica/enzimología , Isquemia Encefálica/epidemiología , Isquemia Encefálica/genética , Hemorragia Cerebral/enzimología , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/genética , Enfermedad de Fabry/enzimología , Enfermedad de Fabry/genética , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/enzimología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Adulto Joven , alfa-Galactosidasa/genéticaRESUMEN
BACKGROUND: There are few reports of anti-myelin oligodendrocyte glycoprotein (MOG) antibody-positive, unilaterally dominant cerebral cortical encephalitis onset with epilepsy. We present such a case in a young female patient with myelitis. CASE PRESENTATION: A 19-year-old female developed generalized tonic seizures lasting several minutes. She had a low-grade fever and headache without other clinical neurological abnormalities while at our hospital. Cerebrospinal fluid (CSF) showed mononuclear pleocytosis. Other laboratory tests indicated no apparent abnormalities. Unilateral meningeal hyperintensity was seen on T2 fluid-attenuated inversion recovery MRI with associated cortical swelling and gadolinium enhancement of the cortical layer. One thousand mg/day of levetiracetam and a 3-day course of intravenous methylprednisolone at 1000â¯mg/day were administered. Dysuria appeared on the twentieth day of illness, and spinal MRI revealed a longitudinally extensive cord lesion from C5 to L1 consistent with myelitis. Two cycles of a 3-day course of intravenous methylprednisolone at 1000â¯mg/day were administered, and all symptoms disappeared. We found the patient to be anti-MOG antibody-positive using serum and CSF (titer: serum 1:256; CSF 1:128). CONCLUSION: Our report illustrates a unique case of anti-MOG presenting as new onset epilepsy secondary to unilaterally dominant meningoencephalitis preceding the onset of longitudinally extensive transverse myelitis.
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Autoanticuerpos/sangre , Lateralidad Funcional/fisiología , Meningoencefalitis/sangre , Meningoencefalitis/etiología , Glicoproteína Mielina-Oligodendrócito/inmunología , Mielitis Transversa/complicaciones , Femenino , Humanos , Imagen por Resonancia Magnética , Meningoencefalitis/diagnóstico por imagen , Mielitis Transversa/diagnóstico por imagen , Adulto JovenRESUMEN
RATIONALE: Only few cases of myasthenia gravis (MG) associated with small-cell lung cancer (SCLC) have been reported, and cases positive for acetylcholine receptor antibody (AChR-ab) are even rarer. The efficacy of standard MG treatment, such as cholinesterase inhibitor therapy, immunosuppressive therapy using steroids and immunosuppressive drugs, plasma exchange, and intravenous immune globulin (IVIg), for these cases is unclear. PATIENT CONCERNS AND DIAGNOSES: A 71-year-old man complained of bilateral eyelid ptosis. He also presented with dysphagia and masticatory muscle fatigue after chewing. The edrophonium test was positive, and the serum AChR-ab level was increased; therefore, the patient was diagnosed with MG. Computed tomography scan showed a nodule on the left upper lobe of the lung and mediastinal lymphadenopathy. Further examination revealed the lesion as SCLC. Finally, he was diagnosed with AChR-ab-positive MG associated with SCLC. INTERVENTIONS AND OUTCOMES: Oral pyridostigmine and tacrolimus were administered to treat MG; however, his symptoms worsened. Therefore, methylprednisolone and IVIg were administrated, which temporarily improved his symptoms. However, they remained uncontrolled. Meanwhile, chemotherapy with carboplatin and etoposide was administered to treat his SCLC. The lesions shrunk, and the MG symptoms and serum AChR-ab level also improved. LESSONS: AChR-ab-positive MG may develop as a comorbidity of SCLC. In such cases, management might require treatment for SCLC in addition to the standard MG treatment to stabilize the MG symptoms.
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Autoanticuerpos/sangre , Neoplasias Pulmonares/inmunología , Miastenia Gravis/inmunología , Receptores Colinérgicos/inmunología , Carcinoma Pulmonar de Células Pequeñas/inmunología , Anciano , Humanos , Neoplasias Pulmonares/sangre , Masculino , Miastenia Gravis/sangre , Carcinoma Pulmonar de Células Pequeñas/sangreRESUMEN
Objective To investigate the clinical symptoms, the physical and neurological findings, and the clinical course of neurological complications in eosinophilic granulomatosis with polyangiitis (EGPA). Methods A retrospective chart review of EGPA cases managed by two referral hospitals was performed, with a focus on the neurological findings. The study analyzed the symptoms at the onset of EGPA and investigated their chronological relationship. The patient delay (the delay between the onset of symptoms and the initial consultation), and the physician delay (the delay from consultation to the initiation of therapy) were determined and compared. The involved nerves were identified thorough a neurological examination. The cases with central nervous system (CNS) involvement were described. Results The average duration of symptoms prior to the initiating of therapy for sensory disturbances, motor deficits, rash, edema, and fever was 23, 5, 21, 18, and 24 days, respectively. Among the EGPA-specific symptoms, sensory disturbance was often the first symptom (63%), and was usually followed by the appearance of rash within four days (63%). The average physician delay (32.9±38.3 days) was significantly longer than the average patient delay (7.9±7.8 days; p=0.010). Reduced touch sensation in the superficial peroneal area, and weakness of dorsal flexion of the first toe secondary to deep peroneal nerve involvement, were highly sensitive for identifying the presence of peripheral nerve involvement in our series of patients with EGPA. Two cases, with CNS involvement, had multiple skin lesions over their hands and feet (Janeway lesions). Conclusion Japanese physicians are not always familiar with EGPA. It is important for us to consider this disease, when an asthmatic patient complains about the new onset of an abnormal sensation in the distal lower extremities, which is followed several days later by rash.
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Granulomatosis con Poliangitis/epidemiología , Enfermedades del Sistema Nervioso/epidemiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Físico , Estudios Retrospectivos , Tiempo de TratamientoRESUMEN
Lupus myelitis (LM) is a rare but serious complication of systemic lupus erythematosus (SLE). In 2009, Birnbaum et al. suggested that LM could be classified into two subtypes, namely gray and white matter myelitis, based on neurological examination findings. Here we describe three cases of this disorder, one with signs of white matter dysfunction and two with signs of gray matter dysfunction. We discuss the potential role of autoantibodies in the development of LM.
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BACKGROUND: The importance of rehabilitation therapy in Parkinson's disease is well recognized. However, the effects of an inpatient rehabilitation program for advanced Parkinson's disease have not been fully investigated. AIM: To assess the effects of intensive inpatient rehabilitation. METHODS: We enrolled 31 patients (mean age 69.5 ± 9.4 years; mean disease duration 8.8 ± 6.4 years) with advanced Parkinson's disease, without severe cognitive impairment. The median Hoehn-Yahr stage was IV. Patients received 2 h of individualized rehabilitation for 6-7 days each week for 1 month. At hospital discharge, patients and caregivers were instructed to continue daily exercise. RESULTS: Motor and total scores of Functional Independence Measures significantly improved between admission and discharge in patients with stage III and IV disease, but not stage V. There was no significant effect of Hoehn-Yahr stage on improvements in Unified Parkinson's Disease Rating Scale scores, (total, part I, II or III), cognitive Functional Independence Measures or Berg Balance Scale. CONCLUSION: Intensive inpatient rehabilitation was effective even in advanced Parkinson's disease. Intensive inpatient rehabilitation, together with home and day-care exercise, might counteract the progressive motor decline in Parkinson's disease.
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Aortic dissection is an infrequent but important cause of acute ischemic stroke (AIS), and must not be overlooked because of a possible worse outcome, especially with the use of an intravenous recombinant tissue plasminogen activator. We report a case of left carotid artery dissection and AIS originating from localized aortic arch dissection, pathologically caused by cystic medial necrosis in the tunica media.
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Aneurisma de la Aorta Torácica/complicaciones , Disección Aórtica/complicaciones , Isquemia Encefálica/etiología , Enfermedades de las Arterias Carótidas/etiología , Quistes/complicaciones , Accidente Cerebrovascular/etiología , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico , Aneurisma de la Aorta Torácica/cirugía , Aortografía/métodos , Implantación de Prótesis Vascular , Isquemia Encefálica/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Angiografía Cerebral/métodos , Angiografía por Tomografía Computarizada , Quistes/diagnóstico , Quistes/cirugía , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
A 76-year-old woman was admitted to our hospital because of transthyretin-related familial amyloid polyneuropathy (TTR-FAP). She had developed bilateral vitreous opacity at the age of 58 and paroxysmal atrial fibrillation at the age of 62. She suffered gait disturbance and dysesthesia of the limbs at the age of 68 and was diagnosed with FAP involving a homozygous Val30Met mutation in the amyloidogenic transthyretin (ATTR) gene after a genetic test. Her parents were cousins, and her aunt's medical history included pacemaker implantation and polyneuropathy. At the age of 74, the patient developed gait disturbance and dysesthesia of her extremities. A neurological examination revealed visual loss, hearing impairment, distal muscle weakness, dysesthesia, and decreased sensation in all modalities in her extremities. She could neither walk nor remain standing without support. Brain magnetic resonance imaging (MRI) revealed a low intensity lesion on the surface of the cerebellum on T2*-weighted images and susceptibility-weighted images. A low intensity pattern that was indicative of the classical type of superficial siderosis was detected. At the age of 76, when she was admitted to our hospital because of the deterioration of her gait disturbance and dysesthesia, brain MRI showed that the patient's cerebellar atrophy and hemosiderin deposition had worsened. Some reports suggest that FAP patients that are homozygous for the ATTR Val30Met mutation are more likely to develop central nervous involvement than those that are heterozygous for the mutation. Superficial siderosis may be responsible for the central nervous involvement.
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Neuropatías Amiloides Familiares/diagnóstico , Neuropatías Amiloides Familiares/genética , Homocigoto , Mutación , Prealbúmina/genética , Siderosis/complicaciones , Anciano , Neuropatías Amiloides Familiares/complicaciones , Atrofia , Enfermedades del Sistema Nervioso Central/etiología , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Femenino , Pruebas Genéticas , Hemosiderina/metabolismo , Humanos , Imagen por Resonancia Magnética , Siderosis/diagnóstico , Siderosis/metabolismoRESUMEN
Several studies have indicated that approximately 25 % of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B2 or urinary 11-dehydro TXB2. Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8 %). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients.