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INTRODUCTION: Tacrolimus-associated neurotoxicity (TAN) manifests with wide clinical spectrum, ranging from mild tremors to severe encephalopathy. The isolated involvement of the brainstem is a rarely documented presentation of TAN, and its clinical and diagnostic characteristics are unclear. METHODS: We report two cases of brainstem-isolated TAN (bi-TAN). Moreover, we performed a systematic review of the literature on bi-TAN and extracted data concerning demographics, clinical characteristics, radiological features, and management. The systematic literature search followed PRISMA guidelines and a pre-defined protocol. RESULTS: Eleven patients, including our two, were identified (mean age: 41.3 years, ± 18.8; five males, 45%). Speech disturbance was the most common clinical presentation (45%). The mean latency from Tacrolimus initiation to bi-TAN onset was 26 days (± 30.8). Tacrolimus serum level tested above the reference range in three patients (mean: 26.83 ± 5.48). Brain MRI showed T2-FLAIR hyperintensities; three showed restricted diffusion on ADC maps. Neurological symptoms resolved completely in seven patients (63%) after Tacrolimus withdrawal or dose reduction. CONCLUSIONS: Our findings suggest that bi-TAN could represent a brainstem variant of posterior reversible encephalopathy syndrome. Recognition of bi-TAN as a potential cause of isolated brainstem lesions is crucial to disentangle the diagnostic work-up and ensure prompt withdrawal or reduction of the offending agent.
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Tronco Encefálico , Inmunosupresores , Síndromes de Neurotoxicidad , Tacrolimus , Humanos , Tacrolimus/efectos adversos , Masculino , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/efectos de los fármacos , Tronco Encefálico/patología , Adulto , Síndromes de Neurotoxicidad/etiología , Inmunosupresores/efectos adversos , Femenino , Persona de Mediana EdadRESUMEN
PURPOSE: We aim to propose a visual quantitative score for muscle edema in lower limb MRI to contribute to the diagnosis of idiopathic inflammatory myopathy (IIM). MATERIAL AND METHODS: We retrospectively evaluated 85 consecutive patients (mean age 57.4 ± 13.9 years; 56.5% female) with suspected IIM (muscle weakness and/or persistent hyper-CPK-emia with/without myalgia) who underwent MRI of lower limbs using T2-weighted fast recovery-fast spin echo images and fat-sat T2 echo planar images. Muscle inflammation was evaluated bilaterally in 11 muscles of the thigh and eight muscles of the leg. Edema in each muscle was graded according to a four-point Likert-type scale adding up to 114 points ([11 + 8)] × 3 × 2). Diagnostic accuracy of the total edema score was explored by assessing sensitivity and specificity using the area under the ROC curve. Final diagnoses were made by a multidisciplinary Expert Consensus Panel applying the Bohan and Peter diagnostic criteria whenever possible. RESULTS: Of the 85 included patients, 34 (40%) received a final diagnosis of IIM (IIM group) while 51 (60%) received an alternative diagnosis (non-IIM group). A cutoff score ≥ 18 was able to correctly classify patients having an IIM with an area under the curve of 0.85, specificity of 96%, and sensitivity of 52.9%. CONCLUSION: Our study demonstrates that a quantitative MRI score for muscle edema in the lower limbs (thighs and legs) aids in distinguishing IIM from conditions that mimic it.
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Edema , Extremidad Inferior , Imagen por Resonancia Magnética , Miositis , Humanos , Femenino , Masculino , Persona de Mediana Edad , Imagen por Resonancia Magnética/normas , Imagen por Resonancia Magnética/métodos , Miositis/diagnóstico por imagen , Miositis/diagnóstico , Estudios Retrospectivos , Extremidad Inferior/diagnóstico por imagen , Edema/diagnóstico por imagen , Anciano , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/patología , Adulto , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Features and prognosis of capsular warning syndrome (CWS) have been poorly investigated prospectively. AIMS: The study aimed to characterize CWS clinical features, risk profile, short- and long-term prognosis, among a large TIA cohort. METHODS: Prospective cohort study of consecutive TIAs was conducted from August 1, 2010, to December 31, 2017. Demographic and clinical characteristics, risk profile, primary (stroke and composite outcome) and secondary (TIA recurrence, cerebral hemorrhage, new onset atrial fibrillation) outcomes were compared between CWS, lacunar (L), and nonlacunar (NL) TIAs. RESULTS: 1,035 patients (33 CWS, 189 L-TIAs, 813 NL-TIAs) were enrolled. Newly diagnosed (ND) hypertension, hypercholesterolemia, cigarette smoking, and leukoaraiosis were independent risk factors of CWS (p < 0.05). CWS showed the highest stroke (30.3% vs. 0.5% and 1.5% for L-TIAs and NL-TIAs, respectively) and composite outcome risk at follow-up (p < 0.001), but better 3-month post-stroke prognosis (mRS 0-2 90.0% vs. 36.8%; p = 0.002). CWS-related stroke mostly occurred <48 h (80.0%) and had a small vessel occlusion etiology (100%), affecting more often the internal capsule (60.0%). Dual antiplatelet therapy (DAPT) versus single antiplatelet therapy was associated with lower 3-month cumulative stroke incidence (12.5% vs. 57.1%; p = 0.010). Intravenous thrombolysis (IVT) showed similar 3-month efficacy and safety in strokes after TIAs groups (median mRS 0, IQR 0-1; p = 0.323). CONCLUSIONS: CWS is associated with higher stroke risk and better functional prognosis than L- and NL-TIAs. CWS risk profile is consistent with severe small vessel disease, and ND hypertension could represent a major risk factor. DAPT and IVT seem effective and safe in preventing and treating stroke following CWS.
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Hipertensión , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Humanos , Ataque Isquémico Transitorio/diagnóstico , Estudios Prospectivos , Pronóstico , Accidente Cerebrovascular/epidemiología , Factores de Riesgo , Hipertensión/complicacionesRESUMEN
mitochondrial neuro-gastrointestinal encephalomyopathy (MNGIE) is a rare genetic disorder characterized by thymidine phosphorylase (TP) enzyme defect. The absence of TP activity induces the imbalance of mitochondrial nucleotide pool, leading to impaired mitochondrial DNA (mtDNA) replication and depletion. Since mtDNA is required to ensure oxidative phosphorylation, metabolically active tissues may not achieve sufficient energy production. The only effective life-saving approach in MNGIE has been the permanent replacement of TP via allogeneic hematopoietic stem cell or liver transplantation. However, the follow-up of transplanted patients showed that gut tissue changes do not revert and fatal complications, such as massive gastrointestinal bleeding, can occur. The purpose of this study was to clarify whether the reintroduction of TP after transplant can recover mtDNA copy number in a normal range. Using laser capture microdissection and droplet-digital-PCR, we assessed the mtDNA copy number in each layer of full-thickness ileal samples of a naive MNGIE cohort vs. controls and in a patient pre- and post-TP replacement. The treatment led to a significant recovery of gut tissue mtDNA amount, thus showing its efficacy. Our results indicate that a timely TP replacement is needed to maximize therapeutic success before irreversible degenerative tissue changes occur in MNGIE.
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Trasplante de Hígado , Errores Innatos del Metabolismo , Encefalomiopatías Mitocondriales , ADN Mitocondrial/genética , Humanos , Íleon , Captura por Microdisección con Láser , Rayos Láser , Encefalomiopatías Mitocondriales/genética , Encefalomiopatías Mitocondriales/terapiaRESUMEN
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by thymidine phosphorylase (TP) enzyme defect. As gastrointestinal changes do not revert in patients undergone TP replacement therapy, one can postulate that other unexplored mechanisms contribute to MNGIE pathophysiology. Hence, we focused on the local TP angiogenic potential that has never been considered in MNGIE. In this study, we investigated the enteric submucosal microvasculature and the effect of hypoxia on fibrosis and enteric neurons density in jejunal full-thickness biopsies collected from patients with MNGIE. Orcein staining was used to count blood vessels based on their size. Fibrosis was assessed using the Sirius Red and Fast Green method. Hypoxia and neoangiogenesis were determined via hypoxia-inducible-factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) protein expression, respectively. Neuron-specific enolase was used to label enteric neurons. Compared with controls, patients with MNGIE showed a decreased area of vascular tissue, but a twofold increase of submucosal vessels/mm2 with increased small size and decreased medium and large size vessels. VEGF positive vessels, fibrosis index, and HIF-1α protein expression were increased, whereas there was a diminished thickness of the longitudinal muscle layer with an increased interganglionic distance and reduced number of myenteric neurons. We demonstrated the occurrence of an angiopathy in the GI tract of patients with MNGIE. Neoangiogenetic changes, as detected by the abundance of small size vessels in the jejunal submucosa, along with hypoxia provide a morphological basis to explain neuromuscular alterations, vasculature breakdown, and ischemic abnormalities in MNGIE.NEW & NOTEWORTHY Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is characterized by a genetically driven defect of thymidine phosphorylase, a multitask enzyme playing a role also in angiogenesis. Indeed, major gastrointestinal bleedings are life-threatening complications of MNGIE. Thus, we focused on jejunal submucosal vasculature and showed intestinal microangiopathy as a novel feature occurring in this disease. Notably, vascular changes were associated with neuromuscular abnormalities, which may explain gut dysfunction and help to develop future therapeutic approaches in MNGIE.
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Tracto Gastrointestinal/metabolismo , Seudoobstrucción Intestinal/metabolismo , Encefalomiopatías Mitocondriales/metabolismo , Distrofia Muscular Oculofaríngea/metabolismo , Neovascularización Patológica/metabolismo , Oftalmoplejía/congénito , Tracto Gastrointestinal/patología , Humanos , Seudoobstrucción Intestinal/patología , Encefalomiopatías Mitocondriales/patología , Distrofia Muscular Oculofaríngea/patología , Neovascularización Patológica/patología , Oftalmoplejía/metabolismo , Oftalmoplejía/patología , Timidina Fosforilasa/metabolismoRESUMEN
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow-up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on 30 March to 31 March 2019, aimed at an evidence-based consensus on diagnosis, prognosis, and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (a) diagnostic pathway; (b) prognosis and the main predictors of disease progression; (c) efficacy and safety of treatments; and (f) research priorities on diagnosis, prognosis, and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence-based guidance for clinicians incorporating patients' values and preferences.
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Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/terapia , Encefalomiopatías Mitocondriales/diagnóstico , Encefalomiopatías Mitocondriales/terapia , Consenso , ADN Mitocondrial/genética , Enfermedades Gastrointestinales/genética , Enfermedades Gastrointestinales/metabolismo , Humanos , Cooperación Internacional , Encefalomiopatías Mitocondriales/genética , Encefalomiopatías Mitocondriales/metabolismo , Mutación , Timidina Fosforilasa/genética , Timidina Fosforilasa/metabolismoRESUMEN
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal, recessive disease caused by mutations in the gene encoding thymidine phosphorylase, leading to reduced enzymatic activity, toxic nucleoside accumulation, and secondary mitochondrial DNA damage. Thymidine phosphorylase replacement has been achieved by allogeneic hematopoietic stem cell transplantation, a procedure hampered by high mortality. Based on high thymidine phosphorylase expression in the liver, a 25-year-old severely affected patient underwent liver transplantation. Serum levels of toxic nucleosides rapidly normalized. At 400 days of follow-up, the patient's clinical conditions are stable. We propose liver transplantation as a new therapy for MNGIE. Ann Neurol 2016;80:448-455.
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Seudoobstrucción Intestinal/cirugía , Trasplante de Hígado/métodos , Encefalomiopatías Mitocondriales/cirugía , Adulto , Humanos , Masculino , Distrofia Muscular Oculofaríngea , Oftalmoplejía/congénitoRESUMEN
Friedreich's ataxia (FRDA) is the commonest autosomal recessive ataxia, caused by GAA triplet expansion in the frataxin gene. Neuropathological studies in FRDA demonstrate that besides the primary neurodegeneration of the dorsal root ganglia, there is a progressive atrophy of the cerebellar dentate nucleus. Diffusion-weighted imaging (DWI) detected microstructural alterations in the cerebellum of FRDA patients. To investigate the biochemical basis of these alterations, we used both DWI and proton MR spectroscopy (1H-MRS) to study the same cerebellar volume of interest (VOI) including the dentate nucleus. DWI and 1H-MRS study of the left cerebellar hemisphere was performed in 28 genetically proven FRDA patients and 35 healthy controls. In FRDA mean diffusivity (MD) values were calculated for the same 1H-MRS VOI. Clinical severity was evaluated using the International Cooperative Ataxia Rating Scale (ICARS). FRDA patients showed a significant reduction of N-acetyl-aspartate (NAA), a neuroaxonal marker, and choline (Cho), a membrane marker, both expressed relatively to creatine (Cr), and increased MD values. In FRDA patients NAA/Cr negatively correlated with MD values (r = -0.396, p = 0.037) and with ICARS score (r = -0.669, p < 0.001). Age-normalized NAA/Cr loss correlated with the GAA expansion (r = -0.492, p = 0.008). The reduced cerebellar NAA/Cr in FRDA suggests that neuroaxonal loss is related to the microstructural changes determining higher MD values. The correlation between NAA/Cr and the severity of disability suggests that this biochemical in vivo MR parameter might be a useful biomarker to evaluate therapeutic interventions.
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Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Imagen de Difusión por Resonancia Magnética , Ataxia de Friedreich/diagnóstico por imagen , Ataxia de Friedreich/metabolismo , Espectroscopía de Protones por Resonancia Magnética , Adolescente , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Cerebelo/efectos de los fármacos , Niño , Colina/metabolismo , Femenino , Ataxia de Friedreich/tratamiento farmacológico , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Fármacos Neuroprotectores/uso terapéutico , Índice de Severidad de la Enfermedad , Ubiquinona/análogos & derivados , Ubiquinona/uso terapéutico , Adulto JovenRESUMEN
Very few cases of patients with myasthenia gravis (MG) who later developed amyotrophic lateral sclerosis (ALS) have been described, although some studies showed that significantly more cases than expected have ALS associated with a prior diagnosis of autoimmune diseases. Our aim was to investigate whether the association of ALS and MG was higher than expected in a population-based study and to describe the clinical features characterizing these patients. In Emilia Romagna Region of Italy, a prospective registry has been collecting all incident ALS cases since 1.1.2009. For each patient, detailed clinical information is collected by caring physicians, including comorbidities. From 1.1.2009 to 31.12.2014, 671 patients were diagnosed with ALS; five patients (0.75%) were also affected by MG. Considering Western Countries incidence rates the occurrence of both the diseases should be a really exceptional event (7.5/109), compared to our findings (1.87/107) (p < 0.01). Patients with ALS and MG had more frequently a bulbar onset and a fast progressive course. These cases of ALS after MG raise the possibility of potential shared immunological dysfunctions, which may be expression of common pathogenic mechanisms, as well as of shared disease-course modulating events.
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Esclerosis Amiotrófica Lateral/epidemiología , Miastenia Gravis/epidemiología , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Humanos , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Sistema de RegistrosRESUMEN
Mitochondrial neuro-gastro-intestinal encephalomyopathy (MNGIE) is a rare and unavoidably fatal disease due to mutations in thymidine phosphorylase (TP). Clinically it is characterized by gastrointestinal dysfunction, malnutrition/cachexia and neurological manifestations. MNGIE diagnosis remains a challenge mainly because of the complexity and rarity of the disease. Thus, our purposes were to promote a better knowledge of the disease in Emilia-Romagna region (ERR) by creating an accurate and dedicated network; to establish the minimal prevalence of MNGIE in Italy starting from ERR. Blood TP activity level was used as screening test to direct candidates to complete diagnostic work-up. During the study period of 1 year, only 10/71 units of ERR recruited 14 candidates. Their screening did not show TP activity changes. An Italian patient not resident in ERR was actually proved to have MNGIE. At the end of study in Italy there were nine cases of MNGIE; thus, the Italian prevalence of the disease is ~0.15/1,000,000 as a gross estimation. Our study confirms that MNGIE diagnosis is a difficult process which reflects the rarity of the disease and, as a result, a low level of awareness among specialists and physicians. Having available novel therapeutic options (e.g., allogenic hematopoietic stem cell transplantation and, more recently, liver transplantation) and an easy screening test, an early diagnosis should be sought before tissue damage occurs irreversibly.
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Encefalomiopatías Mitocondriales/epidemiología , Mutación/genética , Adulto , Femenino , Humanos , Italia/epidemiología , Lenguaje , Masculino , Persona de Mediana Edad , Encefalomiopatías Mitocondriales/genética , Timidina Fosforilasa/genética , Adulto JovenAsunto(s)
Isquemia Encefálica/diagnóstico , Hipo/etiología , Ilusiones/etiología , Arteria Cerebral Posterior/patología , Accidente Cerebrovascular/diagnóstico , Percepción Visual , Anciano , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Humanos , Masculino , Arteria Cerebral Posterior/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Percepción Visual/fisiologíaRESUMEN
Very few studies examined trend over time of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and factors influencing it; previous studies, then, included only patients attending tertiary ALS Centres. We studied ALSFRS-R decline, factors influencing this trend and survival in a population-based setting. From 2009 onwards, a prospective registry records all incident ALS cases among residents in Emilia Romagna (population: 4.4 million). For each patient, demographic and clinical details (including ALSFRS-R) are collected by caring physicians at each follow-up. Analysis was performed on 402 incident cases (1279 ALSFRS-R assessments). The average decline of the ALSFRS-R was 0.60 points/month during the first year after diagnosis and 0.34 points/month in the second year. ALSFRS-R decline was heterogeneous among subgroups. Repeated measures mixed model showed that ALSFRS-R score decline was influenced by age at onset (p < 0.01), phenotype (p = 0.01), body mass index (BMI) (p < 0.01), progression rate at diagnosis (ΔFS) (p < 0.01), El Escorial Criteria-Revised (p < 0.01), and FVC% at diagnosis (p < 0.01). Among these factors, at multivariate analysis, only age, site of onset and ΔFS independently influenced survival. In this first population-based study on ALSFRS-R trend, we confirm that ALSFRS-R decline is not homogeneous among ALS patients and during the disease. Factors influencing ALSFRS-R decline may not match with those affecting survival. These disease modifiers should be taken into consideration for trials design and in clinical practice during discussions with patients on prognosis.
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Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/mortalidad , Sistema de Registros , Adulto , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Esclerosis Amiotrófica Lateral/diagnóstico , Progresión de la Enfermedad , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
BACKGROUND: Rapid management can reduce the short stroke risk after transient ischaemic attack (TIA), but the long-term effect is still little known. We evaluated 3-year vascular outcomes in patients with TIA after urgent care. METHODS: We prospectively enrolled all consecutive patients with TIA diagnosed by a vascular neurologist and referred to our emergency department (ED). Expedited assessment and best secondary prevention was within 24 h. Endpoints were stroke within 90 days, and stroke, myocardial infarction, and vascular death at 12, 24 and 36 months. RESULTS: Between August 2010 and July 2013, we evaluated 686 patients with suspected TIA; 433 (63%) patients had confirmed TIA. Stroke at 90 days was 2.07% (95% confidence interval (CI), 1.1-3.9) compared with the ABCD2-predicted risk of 9.1%. The long-term stroke risk was 2.6% (95% CI, 1.1-4.2), 3.7% (95% CI, 1.6-5.9) and 4.4% (95% CI, 1.9-6.8) at 12, 24 and 36 months, respectively. The composite outcome of stroke, myocardial infarction, and vascular death was 3.5% (95% CI, 1.7-5.1), 4.9% (95% CI, 2.5-7.4), and 5.6% (95% CI, 2.8-8.3) at 12, 24, and 36 months, respectively. CONCLUSIONS: TIA expedited management driven by vascular neurologists was associated with a marked reduction in the expected early stroke risk and low long-term risk of stroke and other vascular events.
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Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/terapia , Accidente Cerebrovascular/epidemiología , Anciano , Vías Clínicas , Servicio de Urgencia en Hospital , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Accidente Cerebrovascular/etiología , Factores de TiempoRESUMEN
BACKGROUND: Mutations of INF2 represent the major cause of familial autosomal dominant (AD) focal segmental glomerulosclerosis (FSGS). A few patients present neurological symptoms of Charcot-Marie-Tooth (CMT) disease but the prevalence of the association has not been assessed yet. METHODS: We screened 28 families with AD FSGS and identified 8 INF2 mutations in 9 families (32 patients overall), 3 of which were new. Mutations were in all cases localized in the diaphanous-inhibitory domain (DID) of the protein. RESULTS: Clinical features associated with INF2 mutations in our patient cohort included mild proteinuria (1.55 g/L; range 1-2.5) and haematuria as a unique symptom that was recognized at a median age of 21.75 years (range 8-30). Eighteen patients developed end-stage renal disease during their third decade of life; 12 patients presented a creatinine range between 1.2 and 1.5 mg/dL and 2 were healthy at 45 and 54 years of age. CMT was diagnosed in four cases (12.5%); one of these patients presented an already known mutation on exon 2 of INF2, whereas the other patients presented the same mutation on exon 4, a region that was not previously associated with CMT. CONCLUSIONS: We confirmed the high incidence of INF2 mutations in families with AD FSGS. The clinical phenotype was mild at the onset of the disease, but evolution to ESRD was frequent. The incidence of CMT has, for the first time, been calculated here to be 12.5% of mutation carriers. Our findings support INF2 gene analysis in families in which renal failure and/or neuro-sensorial defects are inherited following an AD model.
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Enfermedad de Charcot-Marie-Tooth/genética , Glomeruloesclerosis Focal y Segmentaria/genética , Fallo Renal Crónico/genética , Proteínas de Microfilamentos/genética , Mutación/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Niño , Estudios de Cohortes , Análisis Mutacional de ADN , Cartilla de ADN/química , Cartilla de ADN/genética , Femenino , Forminas , Humanos , Italia , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Fenotipo , Reacción en Cadena de la Polimerasa , Homología de Secuencia de Aminoácido , Adulto JovenRESUMEN
Carotid-cavernous fistulas (CCFs) are rare intracranial vascular malformations. Among the various classifications available, the most recently proposed highlights the strong correlation between venous drainage pattern and clinical presentation. We present the case of a woman in her 70s with a history of transient palsy of the fourth cranial nerve who presented with subacute cervical myelopathy, which was caused by a CCF with venous drainage into the peribulbar and perimedullary plexus.Given this atypical presentation of CCF and the diagnostic challenges it poses, we conducted a comprehensive PubMed search looking for CCFs presenting with cervical myelopathy and our results confirmed their rarity and allowed us to identify clinical elements that may help clinicians diagnose and manage this potentially treatable condition.
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Fístula del Seno Cavernoso de la Carótida , Vértebras Cervicales , Enfermedades de la Médula Espinal , Humanos , Femenino , Fístula del Seno Cavernoso de la Carótida/complicaciones , Fístula del Seno Cavernoso de la Carótida/diagnóstico , Fístula del Seno Cavernoso de la Carótida/terapia , Vértebras Cervicales/diagnóstico por imagen , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/diagnóstico , Enfermedades de la Médula Espinal/complicaciones , Anciano , Imagen por Resonancia MagnéticaRESUMEN
Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, is the standard of care for patients with advanced NSCLC and EGFR-sensitizing mutations. Both in osimertinib pivotal trials and in the post-marketing phase, asymptomatic creatinine phosphokinase elevation and clinically relevant muscle damage have been reported. However, the mechanisms underlying these conditions remain unclear. Herein, we report the first muscle biopsy description of osimertinib-induced myopathy and hypothesize that the mechanisms underpinning muscle toxicity could be driven by hyporegenerative mechanisms and mitochondrial dysfunction with subsequent reduced metabolic endurance, both directly linked to the inhibition of downstream molecular pathways mediated by EGFR in muscle cells.
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Background and aims: Fast-track care have been proved to reduce the short-term risk of stroke after transient ischemic attack (TIA). We aimed to investigate stroke risk and to characterize short- and long-term stroke predictors in a large cohort of TIA patients undergoing fast-track management. Methods: Prospective study, enrolling consecutive TIA patients admitted to a Northern Italy emergency department from August 2010 to December 2017. All patients underwent fast-track care within 24 h of admission. The primary outcome was defined as the first stroke recurrence at 90 days, 12 and 60 months after TIA. Stroke incidence with 95% confidence interval (CI) at each timepoint was calculated using Poisson regression. Predictors of stroke recurrence were evaluated with Cox regression analysis. The number needed to treat (NNT) of fast-track care in preventing 90-day stroke recurrence in respect to the estimates based on baseline ABCD2 score was also calculated. Results: We enrolled 1,035 patients (54.2% males). Stroke incidence was low throughout the follow-up with rates of 2.2% [95% CI 1.4-3.3%] at 90 days, 2.9% [95% CI 1.9-4.2%] at 12 months and 7.1% [95% CI 5.4-9.0%] at 60 months. Multiple TIA, speech disturbances and presence of ischemic lesion at neuroimaging predicted stroke recurrence at each timepoint. Male sex and increasing age predicted 90-day and 60-month stroke risk, respectively. Hypertension was associated with higher 12-month and 60-month stroke risk. No specific TIA etiology predicted higher stroke risk throughout the follow-up. The NNT for fast-track care in preventing 90-day stroke was 14.5 [95% CI 11.3-20.4] in the overall cohort and 6.8 [95% CI 4.6-13.5] in patients with baseline ABCD2 of 6 to 7. Conclusion: Our findings support the effectiveness of fast-track care in preventing both short- and long-term stroke recurrence after TIA. Particular effort should be made to identify and monitor patients with baseline predictors of higher stroke risk, which may vary according to follow-up duration.
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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.
Asunto(s)
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
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment and care of patients with cancer owing to unique features, including the occurrence of the so-called immune-related adverse events (irAEs). A multidisciplinary team, possibly including a cardio-oncology specialist, is warranted to achieve a favorable patient outcome. Cardiovascular toxicity, especially myocarditis, emerged as a life-threatening irAE in the real-word setting, and the European Society of Cardiology has recently published the first guideline on cardio-oncology to increase awareness and promote a standardized approach to tackle this complex multimodal issue, including diagnostic challenges, assessment, treatment, and surveillance of patients with cancer receiving ICIs. In this article, through a question & answer format made up of case vignettes, we offer a clinically oriented overview on the latest advancements of ICI-related cardiovascular toxicity, focusing on myocarditis and associated irAEs (myositis and myasthenia gravis within the so-called overlap syndrome), with the purpose of assisting clinicians and healthcare professionals in daily clinical practice.
Asunto(s)
Antineoplásicos Inmunológicos , Miocarditis , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Antineoplásicos Inmunológicos/efectos adversos , Miocarditis/inducido químicamente , Miocarditis/diagnóstico , Miocarditis/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Oncología MédicaRESUMEN
OBJECTIVE: To systematically review the published cases of bilateral facial palsy (BFP) to gather evidence on the clinical assessment and management of this pathology. METHODS: Following PRISMA statement recommendations, 338 abstracts were screened independently by two authors. Inclusion criteria were research articles of human patients affected by BFP, either central or peripheral; English, Italian, French or Spanish language; availability of the abstract, while exclusion criteria were topics unrelated to FP, and mention of unilateral or congenital FP. Only full-text articles reporting the diagnostic work-up, the management, and the prognosis of the BFP considered for further specific data analysis. RESULTS: A total of 143 articles were included, resulting a total of 326 patients with a mean age of 36 years. The most common type of the paralysis was peripheral (91.7%), and the autoimmune disease was the most frequent aetiology (31.3%). The mean time of onset after first symptoms was 12 days and most patients presented with a grade higher than III. Associated symptoms in idiopathic BFP were mostly non-specific. The most frequently positive laboratory exams were cerebrospinal fluid analysis, autoimmune screening and peripheral blood smear, and the most performed imaging was MRI. Most patients (74%) underwent exclusive medical treatment, while a minority were selected for a surgical or combined approach. Finally, in more than half of cases a complete bilateral recovery (60.3%) was achieved. CONCLUSIONS: BFP is a disabling condition. If a correct diagnosis is formulated, possibilities to recover are elevated and directly correlated to the administration of an adequate treatment.