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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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BACKGROUND AND AIMS: Neurological abnormalities have been frequently reported in individuals with Marfan Syndrome (MFS). However, available data relies solely on retrospective studies predating current diagnostic criteria. METHODS: Cross-sectional study comprehensively investigating neurological abnormalities within a prospective cohort of adults (≥ 18 years) with genetically confirmed MFS referred to an Italian hub center for heritable connective tissue diseases (Jan. 1st - Nov. 15th, 2021). RESULTS: We included a total of 38 individuals (53% female). The commonest neurological symptom was migraine (58%), usually without aura (73%). Neuropsychological testing was generally unremarkable, whilst anxiety and depression were highly prevalent within our cohort (42% and 34%, respectively). The most frequent brain parenchymal abnormality was the presence of cortico-subcortical hypointense spots on brain MRI T2* Gradient-Echo sequences (39%), which were found only in patients with a prior history of aortic surgery. Migraineurs had a higher frequency of brain vessels tortuosity vs. individuals without migraine (73% vs. 31%; p = 0.027) and showed higher average and maximum tortuosity indexes in both anterior and posterior circulation brain vessels (all p < 0.05). At univariate regression analysis, the presence of brain vessels tortuosity was significantly associated with a higher risk of migraine (OR 5.87, CI 95% 1.42-24.11; p = 0.014). CONCLUSIONS: Our study confirms that neurological abnormalities are frequent in individuals with MFS. While migraine appears to be associated with brain vessels tortuosity, brain parenchymal abnormalities are typical of individuals with a prior history of aortic surgery. Larger prospective studies are needed to understand the relationship between parenchymal abnormalities and long-term cognitive outcomes.
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PURPOSE: Dural ectasia (DE) may significantly impact Marfan syndrome (MFS) patients' quality of life due to chronic lower back pain, postural headache and urinary disorders. We aimed to evaluate the association of quantitative measurements of DE, and their evolution over time, with demographic, clinical and genetic characteristics in a cohort of MFS patients. METHODS: We retrospectively included 88 consecutive patients (39% females, mean age 37.1 ± 14.2 years) with genetically confirmed MFS who underwent at least one MRI or CT examination of the lumbosacral spine. Vertebral scalloping (VS) and dural sac ratio (DSR) were calculated from L3 to S3. Likely pathogenic or pathogenic FBN1 variants were categorized as either protein-truncating or in-frame. The latter were further classified according to their impact on the cysteine content of fibrillin-1. RESULTS: Higher values of the systemic score (revised Ghent criteria) were associated with greater DSR at lumbar (p < 0.001) and sacral (p = 0.021) levels. Patients with protein-truncating variants exhibited a greater annual increase in lumbar (p = 0.039) and sacral (p = 0.048) DSR. Mutations affecting fibrillin-1 cysteine content were linked to higher VS (p = 0.009) and DSR (p = 0.038) at S1, along with a faster increase in VS (p = 0.032) and DSR (p = 0.001) in the lumbar region. CONCLUSION: Our study shed further light on the relationship between genotype, dural pathology, and the overall clinical spectrum of MFS. The identification of protein-truncating variants and those impacting cysteine content may therefore suggest closer patient monitoring, in order to address potential complications associated with DE.
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Dura-Máter , Fibrilina-1 , Síndrome de Marfan , Humanos , Síndrome de Marfan/genética , Síndrome de Marfan/diagnóstico por imagem , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Dura-Máter/diagnóstico por imagem , Dura-Máter/patologia , Dilatação Patológica/genética , Dilatação Patológica/diagnóstico por imagem , Fibrilina-1/genética , Adulto Jovem , AdipocinasRESUMO
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 , Imunossupressores , Síndromes Neurotóxicas , Tacrolimo , Humanos , Tacrolimo/efeitos adversos , Masculino , Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/patologia , Adulto , Síndromes Neurotóxicas/etiologia , Imunossupressores/efeitos adversos , Feminino , Pessoa de Meia-IdadeRESUMO
A small number of case reports have documented a link between atlantoaxial dislocation (AAD) and vertebral artery dissection (VAD), but this association has never been described in patients with hereditary connective tissue disorders. We present a case of an 18-year-old female patient, diagnosed with Marfan syndrome since the age of one, who underwent brain MRA for intracranial aneurysm screening revealing tortuosity of the internal carotid and vertebral arteries as well as atlantoaxial dislocation. Since the patient was asymptomatic, a wait-and-see approach was chosen, but a follow-up MRA after 18 months showed the appearance of a dissecting pseudoaneurysm of the V3 segment of the left vertebral artery. Despite the patient being still asymptomatic, it was decided to proceed with C1-C2 stabilization to prevent further vascular complications. Follow-up imaging showed realignment of the atlantoaxial joint and reduction of the dissecting pseudoaneurysm of the left vertebral artery. In our patient, screening MRA has led to the discovery of asymptomatic arterial and skeletal abnormalities which, if left untreated, might have led to severe cerebrovascular complications. Therefore, AAD correction or close monitoring with MRA should be provided to MFS patients with this craniovertebral junction anomaly, even if asymptomatic.
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Falso Aneurisma , Aneurisma Intracraniano , Luxações Articulares , Síndrome de Marfan , Dissecação da Artéria Vertebral , Feminino , Humanos , Adolescente , Dissecação da Artéria Vertebral/diagnóstico , Dissecação da Artéria Vertebral/diagnóstico por imagem , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Falso Aneurisma/diagnóstico , Falso Aneurisma/diagnóstico por imagem , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/anormalidades , Luxações Articulares/complicações , Luxações Articulares/diagnósticoAssuntos
Aneurisma Intracraniano , Síndrome de Marfan , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/etiologia , Síndrome de Marfan/complicações , Síndrome de Marfan/diagnóstico , Síndrome de Marfan/epidemiologia , PrevalênciaRESUMO
INTRODUCTION: Marfan syndrome (MFS) is the most common inherited connective tissue disorder and its association with intracranial aneurysms (ICAs) has been debated for more than two decades. Here, we report the prevalence of ICAs at screening neuroimaging in a population of genetically confirmed MFS patients and present the results of a meta-analysis including our cohort of patients and those of previous studies. PATIENTS AND METHODS: We enrolled 100 consecutive MFS patients, who underwent screening with brain magnetic resonance angiography at our tertiary center between August 2018 and May 2022. We did a PubMed and Web of Science search to retrieve all studies on the prevalence of ICAs in patients with MFS published before November, 2022. RESULTS: Of the 100 patients included in this study (94% Caucasians, 40% females, mean age 38.6 ± 14.6 years), three had an ICA. We pooled the current study with five previously published studies, including a total of 465 patients, 43 of which harbored at least one unruptured ICA, leading to an overall ICA prevalence of 8.9% (95% CI 5.8%-13.3%). DISCUSSION AND CONCLUSION: In our cohort of genetically confirmed MFS patients, the prevalence of ICAs was 3%, which is substantially lower compared to previous studies based on neuroimaging. The high frequency of ICA found in previous studies could be explained by selection bias and lack of genetic testing, which may have led to the inclusion of patients with different connective tissue disorders. Further studies, including several centers and a large number of patients with genetically confirmed MFS, are needed to confirm our results.
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Doenças do Tecido Conjuntivo , Aneurisma Intracraniano , Síndrome de Marfan , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Masculino , Síndrome de Marfan/epidemiologia , Estudos Transversais , Aneurisma Intracraniano/diagnóstico por imagem , Prevalência , Doenças do Tecido Conjuntivo/complicaçõesRESUMO
OBJECTIVE: To investigate neurotoxicity clinical and instrumental features, incidence, risk factors, and early and long-term prognosis in lymphoma patients who received CAR T-cell therapy. METHODS: In this prospective study, consecutive refractory B-cell non-Hodgkin lymphoma patients who received CAR T-cell therapy were included. Patients were comprehensively evaluated (neurological examination, EEG, brain MRI, and neuropsychological test) before and after (two and twelve months) CAR T-cells. From the day of CAR T-cells infusion, patients underwent daily neurological examinations to monitor the development of neurotoxicity. RESULTS: Forty-six patients were included in the study. The median age was 56.5 years, and 13 (28%) were females. Seventeen patients (37%) developed neurotoxicity, characterized by encephalopathy frequently associated with language disturbances (65%) and frontal lobe dysfunction (65%). EEG and brain FDG-PET findings also supported a predominant frontal lobe involvement. The median time at onset and duration were five and eight days, respectively. Baseline EEG abnormalities predicted ICANS development in the multivariable analysis (OR 4.771; CI 1.081-21.048; p = 0.039). Notably, CRS was invariably present before or concomitant with neurotoxicity, and all patients who exhibited severe CRS (grade ≥ 3) developed neurotoxicity. Serum inflammatory markers were significantly higher in patients who developed neurotoxicity. A complete neurological resolution following corticosteroids and anti-cytokines monoclonal antibodies was reached in all patients treated, except for one patient developing a fatal fulminant cerebral edema. All surviving patients completed the 1-year follow-up, and no long-term neurotoxicity was observed. CONCLUSIONS: In the first prospective Italian real-life study, we presented novel clinical and investigative insights into ICANS diagnosis, predictive factors, and prognosis.
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Imunoterapia Adotiva , Linfoma , Síndromes Neurotóxicas , Linfoma/terapia , Síndromes Neurotóxicas/epidemiologia , Imunoterapia Adotiva/efeitos adversos , Estudos Prospectivos , Síndrome da Liberação de Citocina , Humanos , Masculino , Feminino , Incidência , Itália , Biomarcadores , Adulto , Pessoa de Meia-Idade , IdosoRESUMO
Some clinical, laboratory, ECG, and echocardiographic parameters could provide useful indications to assess the probability of cardioembolism or atherothrombosis in cryptogenic strokes. We retrospectively examined 290 patients with ischemic stroke aged ≥60 years, divided into 3 groups: strokes originating from large artery atherothrombosis (n = 92), cardioembolic strokes caused by paroxysmal atrial fibrillation (n = 88) and cryptogenic strokes (n = 110). In addition to echocardiographic and routine clinical-laboratory variables, neutrophil:lymphocyte ratio, red blood cell distribution width, mean platelet volume, P wave and PR interval duration and biphasic inferior P waves, both on admission and after 7 to 10 days, were also considered. By multiple logistic regression, cardioembolic strokes were compared with large artery atherothrombosis strokes, and beta coefficients were rounded to produce a scoring system. Late PR interval ≥188 ms, left atrium ≥4 cm, left ventricular end-diastolic volume <65 ml, and posterior circulation syndrome were associated with paroxysmal atrial fibrillation (positive scores). In contrast, male gender, hypercholesterolemia, and initial platelet count ≥290 × 109/L were associated with atherothrombosis of large arteries (negative scores). The algebraic sum of these scores produced values indicative of cardioembolism if >0 (positive predictive value 89.1%), or of atherothrombosis, if ≤0 (positive predictive value 72.5%). The area under the receiver operating characteristic curve was 0.85. Among cryptogenic strokes, 41.5% had a score >0 (probable atrial fibrillation) and 58.5% had a score ≤0 (possible atherothrombosis). In conclusion, a scoring system based on electrocardiogram, laboratory, clinical and echocardiographic parameters can provide useful guidance for further investigations and secondary prevention in older patients with cryptogenic stroke.
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Fibrilação Atrial , AVC Embólico , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Idoso , Fibrilação Atrial/complicações , Estudos Retrospectivos , AVC Embólico/complicações , Fatores de Risco , Acidente Vascular Cerebral/etiologia , AVC Isquêmico/complicaçõesRESUMO
In post-stroke dysphagia, early identification of patients at highest risk of failing swallowing recovery (SR) would be useful to decide which of them should undergo percutaneous endoscopic gastrostomy. The studies on this subject were numerous but generally based on small statistical samples. In this retrospective study, 1232 patients with ischemic or hemorrhagic stroke (73.7 ± 13.0 years, 51% men) were assessed: 593 non-dysphagic, 351 partially dysphagic and 288 totally dysphagic. Among the latter, 45.1% could not recover oral intake. A score to assess the risk of failing SR was obtained from the group with total dysphagia, and further 210 patients with total post-stroke dysphagia were utilized for validation. A regular progression of stroke severity markers, complications and mortality was observed from non-dysphagic, to partially dysphagic, up to totally dysphagic patients. Among the latter, seven variables were independently associated with failure of SR, and formed the "DIsPHAGIc score": cerebral lesion Diameter ≥ 6 cm (+ 1), left frontal Ischemia (- 1), Partial anterior circulation syndrome (- 1), Hypoxia (+ 1), Antiplatelet drug (+ 1), GCS verbal reaction < 4 (+ 1), Internal capsule ischemia (- 1). The area under the ROC curve was 0.79 (95% CI 0.74-0.85). For total scores ≥ 2 there was a high risk of failing SR, with specificity 76.9%, sensitivity 72.1% and accuracy 74.7%. The application of the DIsPHAGIc score to the validation sample provided almost identical results. The evolution of post-stroke dysphagia towards irreversibility can be predicted by a simple, reproducible and robust scoring system based on 7 variables commonly available during hospitalization.
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Transtornos de Deglutição , Acidente Vascular Cerebral , Masculino , Humanos , Feminino , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/complicações , Deglutição , Estudos Retrospectivos , Gastrostomia/métodos , Acidente Vascular Cerebral/complicaçõesRESUMO
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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Hipertensão , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Ataque Isquêmico Transitório/diagnóstico , Estudos Prospectivos , Prognóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Risco , Hipertensão/complicaçõesRESUMO
BACKGROUND: Hyperglycemic non-diabetic stroke patients have a worse prognosis than both normoglycemic and diabetic patients. Aim of this study was to assess whether hyperglycemia is an aggravating factor or just an epiphenomenon of most severe strokes. METHODS: In this retrospective study, 1219 ischemic or hemorrhagic stroke patients (73.7 ± 13.1 years) were divided into 4 groups: 0 = non-hyperglycemic non-diabetic, 1 = hyperglycemic non-diabetic, 2 = non-hyperglycemic diabetic and 3 = hyperglycemic diabetic. Hyperglycemia was defined as fasting blood glucose ≥ 126 mg/dl (≥ 7 mmol/l) measured the morning after admission, while the diagnosis of diabetes was based on a history of diabetes mellitus or on a glycated hemoglobin ≥ 6.5% (≥ 48 mmol/mol), independently of blood glucose levels. All diabetic patients, except 3, had Type 2 diabetes. The 4 groups were compared according to clinical history, stroke severity indicators, acute phase markers and main short term stroke outcomes (modified Rankin scale ≥ 3, death, cerebral edema, hemorrhagic transformation of ischemic lesions, fever, oxygen administration, pneumonia, sepsis, urinary infection and heart failure). RESULTS: Group 1 patients had more severe strokes, with larger cerebral lesions and higher inflammatory markers, compared to the other groups. They also had a high prevalence of atrial fibrillation, prediabetes, previous stroke and previous arterial revascularizations. In this group, the highest frequencies of cerebral edema, hemorrhagic transformation, pneumonia and oxygen administration were obtained. The prevalence of dependency at discharge and in-hospital mortality were equally high in Group 1 and Group 3. However, in multivariate analyses including stroke severity, cerebral lesion diameter, leukocytes and C-reactive protein, Group 1 was only independently associated with hemorrhagic transformation (OR 2.01, 95% CI 0.99-4.07), while Group 3 was independently associated with mortality (OR 2.19, 95% CI 1.32-3.64) and disability (OR 1.70, 95% CI 1.01-2.88). CONCLUSIONS: Hyperglycemic non-diabetic stroke patients had a worse prognosis than non-hyperglycemic or diabetic patients, but this group was not independently associated with mortality or disability when size, severity and inflammatory component of the stroke were accounted for.
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Brachial plexus injuries are commonly diagnosed clinically, as conventional imaging has a low sensitivity. In recent years, diffusion tensor imaging has established a clinical role in the study of the central nervous system and, while still presenting some limitations due to the technical complexity of the acquisition method, is showing promising results when applied to peripheral nerves. Moreover, deterministic fiber tracking with the Euler's method and multishell acquisition are two novel advances in the field which contribute to enhancing the reliability of the technique reducing the respiratory and inhomogeneity artifacts in this "magnetically complex" region, and better isolating the fibers in a heterogeneous territory. Here, we report a case of brachial plexus traumatic injury, a healthy reference subject, and details on the acquisition protocol of the reconstruction algorithm.
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The aim of our study was to evaluate the association between intracranial arterial tortuosity and cardiovascular outcome in patients with Loeys-Dietz syndrome (LDS). We performed a retrospective analysis of all patients with genetically confirmed LDS who underwent at least one brain MRA at our institution (n = 32); demographic and clinical features were evaluated in relation to the tortuosity of intracranial arteries as measured by tortuosity index (TI), which was calculated using the formula: [(centerline length) / (straight-line length)-1] × 100. Receiver operating characteristic curve analysis for intracranial TI and the binary end point of aortic surgery showed vertebrobasilar TI (VBTI) to be the best classifier among the examined arterial segments (AUC = 0.822). Patients with higher VBTI showed a greater incidence of aortic surgery (p < 0.001) and underwent more surgical and endovascular procedures (p = 0.006), with a higher rate of operations (p = 0.002). Kaplan-Meier analysis showed a significantly longer surgery-free survival in patients with lower arterial tortuosity (p < 0.001). At multivariate analysis, higher VBTI was associated with an increased risk of surgery (p < 0.001), which was independent of gene mutation and patient age. Increased VBTI is a marker of adverse cardiovascular outcome in patients with LDS, which can be easily measured on brain MRA, and may be useful in the management of this heterogeneous patient population.