RESUMEN
OBJECTIVE: To estimate the incidence and describe clinical characteristics and outcome of GBS in COVID-19 patients (COVID19-GBS) in one of the most hit regions during the first pandemic wave, Lombardia. METHODS: Adult patients admitted to 20 Neurological Units between 1/3-30/4/2020 with COVID19-GBS were included as part of a multi-center study organized by the Italian society of Hospital Neuroscience (SNO). RESULTS: Thirty-eight COVID19-GBS patients had a mean age of 60.7 years and male frequency of 86.8%. CSF albuminocytological dissociation was detected in 71.4%, and PCR for SARS-CoV-2 was negative in 19 tested patients. Based on neurophysiology, 81.8% of patients had a diagnosis of AIDP, 12.1% of AMSAN, and 6.1% of AMAN. The course was favorable in 76.3% of patients, stable in 10.5%, while 13.2% worsened, of which 3 died. The estimated occurrence rate in Lombardia ranges from 0.5 to 0.05 GBS cases per 1000 COVID-19 infections depending on whether you consider positive cases or estimated seropositive cases. When we compared GBS cases with the pre-pandemic period, we found a reduction of cases from 165 to 135 cases in the 2-month study period in Lombardia. CONCLUSIONS: We detected an increased incidence of GBS in COVID-19 patients which can reflect a higher risk of GBS in COVID-19 patients and a reduction of GBS events during the pandemic period possibly due to a lower spread of more common respiratory infectious diseases determined by an increased use of preventive measures.
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COVID-19 , Síndrome de Guillain-Barré , Adulto , Humanos , Masculino , Persona de Mediana Edad , COVID-19/complicaciones , COVID-19/epidemiología , SARS-CoV-2 , Síndrome de Guillain-Barré/diagnóstico , Pandemias , Italia/epidemiologíaRESUMEN
Since the nineteenth century several clinical features have been observed in common between migraine and epilepsy (such as episodic attacks, triggering factors, presence of aura, frequent familiarity), but only in recent years researchers have really engaged in finding a common pathogenic mechanism. From studies of disease incidence, we understand how either migraine among patients with epilepsy or epilepsy among migraine patients are more frequent than in the general population. This association may result from a direct causality, by the same environmental risk factors and/or by a common genetic susceptibility. Ischemic events are the most frequent direct causes, especially among women and elderly people: migraine can lead to silent or clinically considerable strokes, and these ones could explain the increased risk of developing epilepsy in people with a history of migraine. Head injuries can lead headache, often with migraine characteristics, and seizures. But there are also many idiopathic cases. The comorbidity migraine-epilepsy might be explained in these cases by a neuronal hyperexcitability, which increases the risk of both diseases: a higher concentration of extracellular glutamate, the main excitatory neurotransmitter, leads in fact as a result a Cortical Spreading Depression (the pathophysiological mechanism at the base of aura) and convulsions; antiepileptic drugs such as topiramate are, therefore, used also in migraine prophylaxis. A genetic link between these two diseases is particularly evident in familial hemiplegic migraine: mutations of ATP1A2, SCN1A and CACNA1A genes, identified in this disease, have also been involved in different types of epilepsy and febrile seizures. The channelopathies, especially engaging sodium and potassium ions, can be the common pathogenic mechanism of migraine and epilepsy. Both migraine and epilepsy also have, compared to the general population, a higher prevalence and incidence of affective disorders such as anxiety, depression and suicidal ideation. Anxiety and depression can be part of symptoms that accompany migraine or seizures. Female patients with a long history of illness and frequent attacks are the most at risk. The impact of these diseases on the quality of life is the most obvious cause of these disorders, furthermore some antiepileptic drugs can have depressive effects on mood; the anxious-depressive disorders often result from the interaction between iatrogenic and psychosocial factor with common neurobiological pathogenesis. A chronic lowering of 5-HT (serotonin) levels has been demonstrated both in migraineurs and in depressed patients; amitriptyline and venlafaxine are the most indicated drugs in the treatment of migraine with comorbid depression currently. Likewise imbalance in dopamine levels has been also demonstrated: a D2 receptor genotype has been directly related to comorbidity migraine-depression. In women, hormonal fluctuations are also crucial, especially in the post-partum and late luteal phase, when the estrogenic reduction, associated with up-regulation of SNPs and down-regulation of serotonergic and GABAergic systems, increases the risk of migraine and depression. Furthermore, central sensitization phenomena have been highlighted in both diseases, and result in a progressive increase in the frequency of attacks up to chronicity and the consequent development of drug resistance and overuse. Further studies will be necessary to deepen the close relationship between these three diseases.
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Depresión de Propagación Cortical/fisiología , Epilepsia/fisiopatología , Trastornos Migrañosos/fisiopatología , Trastornos del Humor/fisiopatología , Electroencefalografía/métodos , Epilepsia/epidemiología , Epilepsia/metabolismo , Humanos , Trastornos Migrañosos/epidemiología , Trastornos Migrañosos/metabolismo , Trastornos del Humor/epidemiología , Trastornos del Humor/metabolismo , Sinapsis/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease METHODS: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis. RESULTS: In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease. CONCLUSIONS: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.
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CADASIL/genética , Angiopatía Amiloide Cerebral Familiar/genética , Enfermedad de Fabry/genética , Pruebas Genéticas , Síndrome MELAS/genética , Síndrome de Marfan/genética , Accidente Cerebrovascular/genética , Adulto , Anciano , CADASIL/complicaciones , Angiopatía Amiloide Cerebral Familiar/complicaciones , Análisis Mutacional de ADN , Enfermedad de Fabry/complicaciones , Femenino , Humanos , Síndrome MELAS/complicaciones , Masculino , Síndrome de Marfan/complicaciones , Persona de Mediana Edad , Mutación , Sistema de Registros , Accidente Cerebrovascular/etiologíaRESUMEN
BACKGROUND AND PURPOSE: Early treatment (i.e. thrombolysis) is crucial for a successful care of ischemic stroke. In the management of stroke, two phases are crucial: the pre-hospital and the in-hospital interval. This work investigated factors influencing pre- and in-hospital delay in a large geographic area of Northern Italy. METHODS: Enrolled were patients presenting with ischemic stroke in four administrative districts of Northern Italy (Como, Lecco, Sondrio and Varese) over a 4-month period. Pre-hospital time and in-hospital time with single management steps were recorded prospectively. Age, gender, recruiting hospital, EMS transport and triage codes, clinical severity and thrombolytic treatment were also recorded. Univariate and multivariate analysis of factors predicting pre- and in-hospital delay were performed. RESULTS: Median pre-hospital time and in-hospital time were, respectively, 120 min (interquartile range, IQR 62-271) and 150 min (IQR 80-214). Pre-hospital time was halved in patients hospitalized via EMS (p<0.001) and clinically more severe (p<0.001). At multivariate analysis, transport code was associated with delay at any time (p<0.05). CONCLUSIONS: EMS use and transport code predicted treatment delay in patients with ischemic stroke. A more intensive use of EMS and high urgency codes could help increase the number of stroke patients treated appropriately.
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Isquemia Encefálica/terapia , Hospitalización , Accidente Cerebrovascular/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Terapia Trombolítica , Factores de Tiempo , Resultado del TratamientoRESUMEN
A potential role for macroautophagy dysfunction in the pathogenesis of amyotrophic lateral sclerosis (ALS) was hypothesized after the demonstration that selected markers are up-regulated in post mortem samples obtained from both patients and animal models of disease. We hypothesized that a putative dysfunction of this catabolic pathway could be operative also in peripheral blood mononuclear cells (PBMC) obtained from ALS patients, since these cells represent an accessible model for studying molecular pathogenesis events in neuropsychiatric disorders. Beclin-1 and LC3II immunoreactivity were assessed in PBMC from 15 ALS patients and 15 controls by Western blot analysis. The expression of Atg12 mRNA was also assessed by real-time PCR. No significant difference was observed for all these parameters between patients and controls, although PBMC displayed a clear macroautophagy induction following exposure to rapamycin and lithium. Finally, we excluded a putative interference of riluzole demonstrating that LC3II immunoreactivity did not change in riluzole-treated SH-SY5Y neuroblastoma cells. In conclusion, the results of our pilot study do not support the idea of a systemic macroautophagic dysfunction in ALS, although they confirm that PBMC are a suitable peripheral marker for monitoring the effects of drugs interfering with this catabolic pathway.
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Esclerosis Amiotrófica Lateral/sangre , Autofagia/fisiología , Biomarcadores/sangre , Leucocitos Mononucleares/metabolismo , Anciano , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Beclina-1 , Células Cultivadas , Femenino , Humanos , Leucocitos Mononucleares/citología , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Persona de Mediana Edad , Fármacos Neuroprotectores/uso terapéutico , Riluzol/uso terapéuticoRESUMEN
BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common familial cerebral small vessel disease, caused by NOTCH3 gene mutations. The aim of our study was to identify clinical and neuroradiological features which would be useful in identifying which patients presenting with lacunar stroke and TIA are likely to have CADASIL. METHODS: Patients with lacunar stroke or TIA were included in the present study. For each patient, demographic and clinical data were collected. MRI images were centrally analysed for the presence of lacunar infarcts, microbleeds, temporal lobe involvement, global atrophy and white matter hyperintensities. RESULTS: 128 patients (mean age 56.3 ± 12.4 years) were included. A NOTCH3 mutation was found in 12.5% of them. A family history of stroke, the presence of dementia and external capsule lesions on MRI were the only features significantly associated with the diagnosis of CADASIL. Although thalamic, temporal pole gliosis and severe white matter hyperintensities were less specific for CADASIL diagnosis, the combination of a number of these factors together with familial history for stroke result in a higher positive predictive value and specificity. CONCLUSIONS: A careful familial history collection and neuroradiological assessment can identify patients in whom NOTCH3 genetic testing has a higher yield.
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Encéfalo/diagnóstico por imagen , CADASIL/diagnóstico , Neuroimagen , Receptor Notch3/genética , Adulto , Anciano , Atrofia , CADASIL/genética , CADASIL/fisiopatología , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/genética , Hemorragia Cerebral/fisiopatología , Femenino , Humanos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/genética , Ataque Isquémico Transitorio/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Accidente Vascular Cerebral Lacunar/diagnóstico , Accidente Vascular Cerebral Lacunar/genética , Accidente Vascular Cerebral Lacunar/fisiopatología , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND AND PURPOSE: Thrombolysis represents the best therapy for ischemic stroke but the main limitation of its administration is time. The avoidable delay is a concept reflecting the effectiveness of management pathway. For this reason, we projected a study concerning the detection of main delays with following introduction of corrective factors. In this paper we describe the results after these corrections. MATERIALS AND METHODS: Consecutive patients admitted for ischemic stroke during a 3-months period to 35 hospitals of a macro-area of Northern Italy were enrolled. Each time of management was registered, identifying three main intervals: pre-hospital, in-hospital and total times. Previous corrective interventions were: 1.increasing of population awareness to use the Emergency Medical Service (EMS); 2.pre-notification of Emergency Department; 3.use of high urgency codes; 4.use of standardised operational algorithm. Statistical analysis was conducted using time-to-event analysis and Cox proportional hazard regression. RESULTS: 1084 patients were enrolled. EMS was alerted for 56.3% of subjects, mainly in females and severe strokes (p<0.001). Thrombolytic treatment was performed in 4.7% of patients. Median pre-hospital and in-hospital times were 113 and 105min, while total time was 240. High urgency codes at transport contributed to reduce pre-hospital and in-hospital time (p<0.05). EMS use and high urgency codes promoted thrombolysis. Treatment within 4.5hours from symptom onset was performed in 14% of patients more than the first phase of study. CONCLUSIONS: The implementation of an organizational system based on EMS and concomitant high urgency codes use was effective to reduce avoidable delay and to increase thrombolysis.
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Servicios Médicos de Urgencia/organización & administración , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/métodos , Anciano , Anciano de 80 o más Años , Manejo de la Enfermedad , Servicios Médicos de Urgencia/estadística & datos numéricos , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Terapia Trombolítica/estadística & datos numéricos , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
The management of the pain therapy (ischemic pain, neoplastic pain) in hemodialysis patients has become a frequent challenge in the last years. These patients often require the prescription of major analgesic drugs such as Opioids like Fentanyl, in order to control the pain. It is necessary to pay attention to the correct dosage and to the half life of these drugs, that results prolonged in the chronic renal insufficiency. The main side effect of opioids is respiratory depression which is well known, however, up to date, there is a lack of reports about other less frequent side effects, such as epilepsy or status epilepticus, in the literature. We report two cases of chronic hemodialysed patients who developed a generalized nonconvulsive status epilepticus secondary to Fentanyl intoxication administered for the pain therapy. These cases required a synergic team management with involvement of the nephrologist, the neurologist and the intensivist. The generalized non convulsive status epilepticus could be an important and serious side effect of Fentanyl in hemodialysis patients and it is therefore necessary a close monitoring of the pain therapy in these subjects.
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Analgésicos Opioides/envenenamiento , Fentanilo/envenenamiento , Diálisis Renal , Estado Epiléptico/inducido químicamente , Anciano , Anciano de 80 o más Años , Femenino , Humanos , MasculinoRESUMEN
Stroke is the leading cause of disability in adulthood, and the principal aim of care in cerebrovascular disease is the reduction of this negative outcome and mortality. Several studies demonstrated the efficacy of thrombolytic therapy in ischemic stroke, but up to 80% of cases could not be treated because the diagnostic workup exceeds the time limit. In this article, we described the design of a study conducted in the northern Lombardy, within the district of Sondrio, Lecco, Como, and Varese. The awaited results of this study are reduction of avoidable delay, organization of an operative stroke emergency network, and identification of highly specialized structures. The study schedules education and data registration with implementation and training of acute stroke management algorithms. The use of standardized protocols during prehospital and in-hospital phase can optimize acute stroke pathways. The results of this study could contribute to the assessment of an effective and homogeneous health system to manage acute stroke.
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Servicios Médicos de Urgencia/organización & administración , Accidente Cerebrovascular/terapia , Algoritmos , Estudios de Casos y Controles , Protocolos Clínicos , Difusión de Innovaciones , Medicina de Emergencia/educación , Hospitalización , Humanos , Relaciones Interprofesionales , Italia , Cuerpo Médico de Hospitales/educación , Estudios Prospectivos , Terapia Trombolítica/normasRESUMEN
A pictorial review was performed (with added acquisition technique optimization guidelines) on CT and MR imaging of intracranial meningeal involvement from infectious or inflammatory origin, on the inherent main differential diagnoses, and on the topography of contiguous extension of lesions.