RESUMEN
OBJECTIVE: Neurodegeneration and neuroinflammation are two intertwined mechanisms contributing to the pathophysiology of Parkinson's disease. Whether circulating biomarkers reflecting those two processes differ according to disease duration remains to be established. The present study was conducted to characterize the biomarkers individuals with PD with short (≤5 years) or long disease duration (>5 years). METHODS: We consecutively enrolled 104 patients with Parkinson's disease and evaluated them using validated clinical scales (MDS-UPDRS, Hoehn and Yahr staging, MMSE). Serum samples were assayed for the following biomarkers: neurofilament light chain (NfL), brain-derived neurotrophic factor (BDNF), interleukin (IL-) 1ß, 4, 5, 6, 10, 17, interferon-γ, and tumor necrosis factor α. RESULTS: Mean age of participants was 66.0 ± 9.6 years and 45 (34%) were women. The average disease duration was 8 ± 5 years (range 1 to 19 years). Patients with short disease duration (≤ 5 years) showed a pro-inflammatory profile, with significantly higher levels of pro-inflammatory IL-1ß and lower concentrations of IL-5, IL-10 and IL-17 (p < 0.05). NfL serum levels showed a positive correlation with disease duration and age (respectively rho = 0.248, p = 0.014 and rho = 0.559, p < 0.001) while an opposite pattern was detected for BDNF (respectively rho -0,187, p = 0.034 and rho = -0.245, p = 0.014). CONCLUSIONS: Our findings suggest that a pro-inflammatory status may be observed in PD patients in the early phases of the disease, independently from age.
Asunto(s)
Citocinas , Enfermedad de Parkinson , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Factor Neurotrófico Derivado del Encéfalo , Factor de Necrosis Tumoral alfa , Biomarcadores , Interleucina-1betaRESUMEN
A 52-year-old man experienced two seizures in January and June 2021. In October, the neurological examination did not reveal sensory/motor deficits. Brain magnetic resonance imaging (MRI) showed hyperintense lesions with contrast enhancement (CE) involving white matter bilaterally, brainstem, and cerebellum. Spine MRI showed hyperintense C2-C3 and C4-C6 lesions with CE. Anti-aquaporin-4 (AQP4) antibodies were detected, confirming the diagnosis of neuromyelitis optica spectrum disorder (NMOSD). The patient experienced a status epilepticus compatible with Epilepsia Partialis Continua treated with antiseizure medications. He was also treated with methylprednisolone, plasma exchange, and rituximab. Status epilepticus can be a rare manifestation of NMOSD, heightening the broad spectrum of AQP4 autoimmunity.
RESUMEN
BACKGROUND AND PURPOSE: Myopathies are associated with classic signs and symptoms, but also with possible life-threatening complications that may require assistance in an emergency setting. This phenomenon is understudied in the literature. We aimed to assess the presentation, management, and outcomes of clinical manifestations potentially related to a muscle disorder requiring referral to the adult emergency department (ED) and hospitalization. METHODS: Anonymized patient data retrieved using the International Classification of Diseases, Ninth Revision codes related to muscle disorders over 4 years were retrospectively analyzed. Medical reports were evaluated to extract demographic and clinical variables, along with outcomes. Two groups were defined based on the presence (known diagnosis [KD] group) or absence (unknown diagnosis [UD] group) of a diagnosed muscle disorder at arrival. RESULTS: A total of 244 patients were included, 51% of whom were affected by a known myopathy, predominantly limb-girdle muscular dystrophies and myotonic dystrophies. The main reasons for ED visits in the KD group were respiratory issues, worsening of muscle weakness, and gastrointestinal problems. Heart complications were less prevalent. In the UD group, 27 patients received a new diagnosis of a specific primary muscle disorder after the ED access, mostly an inflammatory myopathy. Death during hospitalization was recorded in 26 patients, with a higher rate in the KD group and in patients affected by mitochondrial and inflammatory myopathies. Sepsis and dyspnea were associated with increased death risk. CONCLUSIONS: Respiratory complications are the most common reason for myopathic patients accessing the ED, followed by gastrointestinal issues. Infections are severe threats and, once hospitalized, these patients have relatively high mortality.
Asunto(s)
Enfermedades Musculares , Miositis , Adulto , Humanos , Estudios Retrospectivos , Hospitalización , Enfermedades Musculares/epidemiología , Enfermedades Musculares/terapia , Miositis/complicaciones , Miositis/diagnóstico , Miositis/epidemiología , Servicio de Urgencia en Hospital , HospitalesRESUMEN
BACKGROUND: The 30-day hospital re-admission rate is a quality measure of hospital care to monitor the efficiency of the healthcare system. The hospital re-admission of acute stroke (AS) patients is often associated with higher mortality rates, greater levels of disability and increased healthcare costs. The aim of our study was to identify predictors of unplanned 30-day hospital re-admissions after discharge of AS patients and define an early re-admission risk score (RRS). METHODS: This observational, retrospective study was performed on AS patients who were discharged between 2014 and 2019. Early re-admission predictors were identified by machine learning models. The performances of these models were assessed by receiver operating characteristic curve analysis. RESULTS: Of 7599 patients with AS, 3699 patients met the inclusion criteria, and 304 patients (8.22%) were re-admitted within 30 days from discharge. After identifying the predictors of early re-admission by logistic regression analysis, RRS was obtained and consisted of seven variables: hemoglobin level, atrial fibrillation, brain hemorrhage, discharge home, chronic obstructive pulmonary disease, one and more than one hospitalization in the previous year. The cohort of patients was then stratified into three risk categories: low (RRS = 0-1), medium (RRS = 2-3) and high (RRS >3) with re-admission rates of 5%, 8% and 14%, respectively. CONCLUSIONS: The identification of risk factors for early re-admission after AS and the elaboration of a score to stratify at discharge time the risk of re-admission can provide a tool for clinicians to plan a personalized follow-up and contain healthcare costs.
Asunto(s)
Accidente Cerebrovascular , Humanos , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia , Hospitales , Aprendizaje AutomáticoRESUMEN
BACKGROUND AND PURPOSE: Post-stroke movement disorders (PMDs) following ischemic lesions of the basal ganglia (BG) are a known entity, but data regarding their incidence are lacking. Ischemic strokes secondary to proximal middle cerebral artery (MCA) occlusion treated with thrombectomy represent a model of selective damage to the BG. The aim of this study was to assess the prevalence and features of movement disorders after selective BG ischemia in patients with successfully reperfused acute ischemic stroke (AIS). METHODS: We enrolled 64 consecutive subjects with AIS due to proximal MCA occlusion treated with thrombectomy. Patients were clinically evaluated by a movement disorders specialist for PMDs onset at baseline, and after 6 and 12 months. RESULTS: None of the patients showed an identifiable movement disorder in the subacute phase of the stroke. At 6 and 12 months, respectively, 7/25 (28%) and 7/13 (53.8%) evaluated patients developed PMDs. The clinical spectrum of PMDs encompassed parkinsonism, dystonia and chorea, either isolated or combined. In most patients, symptoms were contralateral to the lesion, although a subset of patients presented with bilateral involvement and prominent axial signs. CONCLUSION: Post-stroke movement disorders are not uncommon in long-term follow-up of successfully reperfused AIS. Follow-up conducted by a multidisciplinary team is strongly advisable in patients with selective lesions of the BG after AIS, even if asymptomatic at discharge.
Asunto(s)
Isquemia Encefálica , Corea , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/cirugía , Infarto de la Arteria Cerebral Media/complicaciones , Trombectomía/efectos adversos , Trombectomía/métodos , Ganglios Basales/irrigación sanguínea , Corea/complicaciones , Estudios Retrospectivos , Resultado del Tratamiento , Isquemia Encefálica/complicaciones , Isquemia Encefálica/cirugíaRESUMEN
The critical role of alpha-synuclein in Parkinson's disease represents a pivotal discovery. Some progress has been made over recent years in identifying disease-modifying therapies for Parkinson's disease that target alpha-synuclein. However, these treatments have not yet shown clear efficacy in slowing the progression of this disease. Several explanations exist for this issue. The pathogenesis of Parkinson's disease is complex and not yet fully clarified and the heterogeneity of the disease, with diverse genetic susceptibility and risk factors and different clinical courses, adds further complexity. Thus, a deep understanding of alpha-synuclein physiological and pathophysiological functions is crucial. In this review, we first describe the cellular and animal models developed over recent years to study the physiological and pathological roles of this protein, including transgenic techniques, use of viral vectors and intracerebral injections of alpha-synuclein fibrils. We then provide evidence that these tools are crucial for modelling Parkinson's disease pathogenesis, causing protein misfolding and aggregation, synaptic dysfunction, brain plasticity impairment and cell-to-cell spreading of alpha-synuclein species. In particular, we focus on the possibility of dissecting the pre- and postsynaptic effects of alpha-synuclein in both physiological and pathological conditions. Finally, we show how vulnerability of specific neuronal cell types may facilitate systemic dysfunctions leading to multiple network alterations. These functional alterations underlie diverse motor and non-motor manifestations of Parkinson's disease that occur before overt neurodegeneration. However, we now understand that therapeutic targeting of alpha-synuclein in Parkinson's disease patients requires caution, since this protein exerts important physiological synaptic functions. Moreover, the interactions of alpha-synuclein with other molecules may induce synergistic detrimental effects. Thus, targeting only alpha-synuclein might not be enough. Combined therapies should be considered in the future.
Asunto(s)
Enfermedad de Parkinson , alfa-Sinucleína , Animales , alfa-Sinucleína/metabolismo , Animales Modificados Genéticamente , Modelos Animales de Enfermedad , Neuronas/metabolismo , HumanosRESUMEN
INTRODUCTION: Status Epilepticus (SE) can occur in patients without a previous epilepsy diagnosis, a condition identified as "new-onset status epilepticus" (NOSE). Treatment with benzodiazepine may fail in NOSE termination, requiring anti-seizure medication (ASM) employment. The term "established NOSE" (eNOSE) is generally employed in this context. This study aims to describe the main clinical characteristics of a large sample of patients suffering from eNOSE, compare the ASM efficacy, and explore the risk factors associated with ASM treatment unresponsiveness and eNOSE-associated mortality. METHODS: Adult patients diagnosed with eNOSE were retrospectively selected between January 2016 and December 2022. We reviewed demographics, clinical data, diagnostic work-up, and treatment. We considered the last ASM introduced before the eNOSE termination as effective. RESULTS: 123 patients were included (age: 67.9 ± 17.3). eNOSE acute etiology was mostly reported. In the overall cohort, phenytoin showed the highest response rate (p = 0.01). In the pairwise comparisons, valproate was superior to levetiracetam (p = 0.02) but not to lacosamide (p = 0.50). Phenytoin had a significantly higher resolution rate than levetiracetam (p = 0.001) but not lacosamide (p = 0.14). Thirty patients were refractory to ASM treatment. No predictors of refractoriness were identified. Thirty-nine patients died. Age and GCS were identified as eNOSE-related mortality risk factors. CONCLUSION: eNOSE frequently has an acute etiology with several associated syndromes. Phenytoin is more effective in managing eNOSE, even though lacosamide, valproate, and levetiracetam can represent further therapeutic options. Age and GCS are the main risk factors for eNOSE-associated mortality.
RESUMEN
BACKGROUND: Among university students, migraine is notably prevalent and is linked to compromised academic performance and daily functioning. Medical students are a particularly vulnerable category due to the demanding nature of their training, as they are often exposed to headache trigger factors. We therefore aimed to determine the prevalence, characteristics, and healthcare-seeking practices of primary headaches among Italian medical students. METHODS: We conducted a cross-sectional study among medical students attending the Università Cattolica del Sacro Cuore in Rome who completed a self-administered questionnaire designed following the International Classification of Headache Disorders-3 criteria. The questionnaire assessed sociodemographic and headache features, healthcare utilization, the use of symptomatic and preventive treatment, and headache trigger factors. RESULTS: Five hundred thirty-six students filled out the questionnaire. The lifetime and last-year prevalence of headache in this cohort was 76.7% (n = 411). Among the students surveyed, migraine had a prevalence of 26.9%, probable migraine of 12.9%, and tension-type headache (TTH)/probable TTH of 36.9%. Two hundred and forty-six students (59.8%) reported that their headache worsened after starting university. All students reporting headache had at least one trigger factor. In students fulfilling the criteria for migraine (n = 144), 137 (95.1%) had previously used acute non-prescription treatments, and eight concurrently used a preventive treatment. Thirty-five students fulfilling the criteria for migraine underwent a brain MRI scan (24.3%), 43 performed a neurological evaluation (29.9%), 36 received a diagnosis of migraine (25%), and 20 (13.9%) accessed the emergency room. DISCUSSION: Migraine and TTH are common among medical students in Italy despite low healthcare resource utilization. These results support the need to promote public health policies and strategies in order to reduce the disability and burden associated with primary headaches among medical students.
Asunto(s)
Aceptación de la Atención de Salud , Estudiantes de Medicina , Humanos , Estudiantes de Medicina/estadística & datos numéricos , Femenino , Masculino , Prevalencia , Estudios Transversales , Adulto Joven , Italia/epidemiología , Adulto , Aceptación de la Atención de Salud/estadística & datos numéricos , Trastornos Migrañosos/epidemiología , Encuestas y Cuestionarios , Cefaleas Primarias/epidemiología , Cefalea/epidemiología , Adolescente , Cefalea de Tipo Tensional/epidemiologíaRESUMEN
BACKGROUND: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) is standard of care for Parkinson's disease (PD) patients and a correct lead placement is crucial to obtain good clinical outcomes. Evidence demonstrating the targeting accuracy of the frameless technique for DBS, along with the advantages for patients and clinicians, is solid, while data reporting long-term clinical outcomes for PD patients are still lacking. OBJECTIVES: The study aims to assess the clinical safety and efficacy of frameless bilateral STN-DBS in PD patients at 5 years from surgery. METHODS: Consecutive PD patients undergoing bilateral STN-DBS with a frameless system were included in this single-center retrospective study. Clinical features, including the Unified Parkinson's Disease Rating Scale (UPDRS) in its total motor score and axial sub-scores, and pharmacological regimen were assessed at baseline, 1 year, 3 years, and 5 years after surgery. The adverse events related to the procedure, stimulation, or the presence of the hardware were systematically collected. RESULTS: Forty-one PD patients undergone bilateral STN-DBS implantation were included in the study and fifteen patients already completed the 5-year observation. No complications occurred during surgery and the perioperative phase, and no unexpected serious adverse event occurred during the entire follow-up period. At 5 years from surgery, there was a sustained motor efficacy of STN stimulation: STN-DBS significantly improved the off-stim UPDRS III score at 5 years by 37.6% (P < 0.001), while the dopaminergic medications remained significantly reduced compared to baseline (- 21.6% versus baseline LEDD; P = 0.036). CONCLUSIONS: Our data support the use of the frameless system for STN-DBS in PD patients, as a safe and well-tolerated technique, with long-term clinical benefits and persistent motor efficacy at 5 years from the surgery.
Asunto(s)
Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , Estimulación Encefálica Profunda/efectos adversos , Estimulación Encefálica Profunda/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Núcleo Subtalámico/cirugíaRESUMEN
A few cases of multiple sclerosis (MS) onset after COVID-19 vaccination have been reported, although the evidence is insufficient to establish causality. The aim of this study is to compare cases of newly diagnosed relapsing-remitting MS before and after the outbreak of the COVID-19 pandemic and the impact of COVID-19 vaccination. Potential environmental and genetic predisposing factors were also investigated, as well as clinical patterns. This is a single-centre retrospective cohort study including all patients who presented with relapsing-remitting MS onset between January 2018 and July 2022. Data on COVID-19 vaccination administration, dose, and type were collected. HLA-DRB1 genotyping was performed in three subgroups. A total of 266 patients received a new diagnosis of relapsing-remitting MS in our centre, 143 before the COVID-19 pandemic (until and including March 2020), and 123 during the COVID-19 era (from April 2020). The mean number of new MS onset cases per year was not different before and during the COVID-19 era and neither were baseline patients' characteristics, type of onset, clinical recovery, or radiological patterns. Fourteen (11.4%) patients who subsequently received a new diagnosis of MS had a history of COVID-19 vaccination within one month before symptoms onset. Patients' characteristics, type of onset, clinical recovery, and radiological patterns did not differ from those of patients with non-vaccine-related new diagnoses of MS. The allele frequencies of HLA-DRB1*15 were 17.6% and 22.2% in patients with non-vaccine-related disease onset before and during the COVID-19 era, respectively, while no case of HLA-DRB1*15 was identified among patients with a new diagnosis of MS post-COVID-19 vaccine. In contrast, HLA-DRB1*08+ or HLA-DRB1*10+ MS patients were present only in this subgroup. Although a causal link between COVID-19 vaccination and relapsing-remitting MS cannot be detected, it is interesting to note and speculate about the peculiarities and heterogeneities underlying disease mechanisms of MS, where the interactions of genetics and the environment could be crucial also for the follow-up and the evaluation of therapeutic options.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Cadenas HLA-DRB1 , Haplotipos , SARS-CoV-2 , Humanos , Femenino , Masculino , Cadenas HLA-DRB1/genética , Adulto , COVID-19/genética , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Estudios Retrospectivos , SARS-CoV-2/genética , SARS-CoV-2/inmunología , Persona de Mediana Edad , Vacunación , Esclerosis Múltiple Recurrente-Remitente/genética , Esclerosis Múltiple Recurrente-Remitente/inmunología , Esclerosis Múltiple/genética , Predisposición Genética a la EnfermedadRESUMEN
The implications of neurogenic inflammation and neuroinflammation in the pathophysiology of migraine have been clearly demonstrated in preclinical migraine models involving several sites relevant in the trigemino-vascular system, including dural vessels and trigeminal endings, the trigeminal ganglion, the trigeminal nucleus caudalis as well as central trigeminal pain processing structures. In this context, a relevant role has been attributed over the years to some sensory and parasympathetic neuropeptides, in particular calcitonin gene neuropeptide, vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Several preclinical and clinical lines of evidence also support the implication of the potent vasodilator and messenger molecule nitric oxide in migraine pathophysiology. All these molecules are involved in vasodilation of the intracranial vasculature, as well as in the peripheral and central sensitization of the trigeminal system. At meningeal level, the engagement of some immune cells of innate immunity, including mast-cells and dendritic cells, and their mediators, has been observed in preclinical migraine models of neurogenic inflammation in response to sensory neuropeptides release due to trigemino-vascular system activation. In the context of neuroinflammatory events implicated in migraine pathogenesis, also activated glial cells in the peripheral and central structures processing trigeminal nociceptive signals seem to play a relevant role. Finally, cortical spreading depression, the pathophysiological substrate of migraine aura, has been reported to be associated with inflammatory mechanisms such as pro-inflammatory cytokine upregulation and intracellular signalling. Reactive astrocytosis consequent to cortical spreading depression is linked to an upregulation of these inflammatory markers. The present review summarizes current findings on the roles of immune cells and inflammatory responses in the pathophysiology of migraine and their possible exploitation in the view of innovative disease-modifying strategies.
Asunto(s)
Trastornos Migrañosos , Inflamación Neurogénica , Humanos , Enfermedades Neuroinflamatorias , Ganglio del Trigémino , Polipéptido Hipofisario Activador de la Adenilato-CiclasaRESUMEN
Loss of dopaminergic midbrain neurons perturbs l-serine and d-serine homeostasis in the post-mortem caudate putamen (CPu) of Parkinson's disease (PD) patients. However, it is unclear whether the severity of dopaminergic nigrostriatal degeneration plays a role in deregulating serine enantiomers' metabolism. Here, through high-performance liquid chromatography (HPLC), we measured the levels of these amino acids in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and MPTP-plus-probenecid (MPTPp)-treated mice to determine whether and how dopaminergic midbrain degeneration affects the levels of serine enantiomers in various basal ganglia subregions. In addition, in the same brain regions, we measured the levels of key neuroactive amino acids modulating glutamatergic neurotransmission, including l-glutamate, glycine, l-aspartate, d-aspartate, and their precursors l-glutamine, l-asparagine. In monkeys, MPTP treatment produced severe denervation of nigrostriatal dopaminergic fibers (â75%) and increased the levels of serine enantiomers in the rostral putamen (rPut), but not in the subthalamic nucleus, and the lateral and medial portion of the globus pallidus. Moreover, this neurotoxin significantly reduced the protein expression of the astrocytic serine transporter ASCT1 and the glycolytic enzyme GAPDH in the rPut of monkeys. Conversely, concentrations of d-serine and l-serine, as well as ASCT1 and GAPDH expression were unaffected in the striatum of MPTPp-treated mice, which showed only mild dopaminergic degeneration (â30%). These findings unveil a link between the severity of dopaminergic nigrostriatal degeneration and striatal serine enantiomers concentration, ASCT1 and GAPDH expression. We hypothesize that the up-regulation of d-serine and l-serine levels occurs as a secondary response within a homeostatic loop to support the metabolic and neurotransmission demands imposed by the degeneration of dopaminergic neurons.
Asunto(s)
1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Serina , Ratones , Animales , Serina/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Dopamina/metabolismo , Cuerpo Estriado/metabolismo , Mesencéfalo/metabolismo , Aminoácidos/metabolismo , Putamen/metabolismo , HomeostasisRESUMEN
INTRODUCTION: CSF Neurofilament light chain(NfL) is a promising biomarker of neurodegeneration, but its utility in discriminating between Alzheimer's disease(AD) and frontotemporal dementia(FTD) is limited. METHODS: 105 patients with clinical-biological diagnosis of mild cognitive impairment(MCI) due to AD (N = 72) or clinical diagnosis of FTD (N = 33) underwent neuropsychological assessment and CSF Aß42/40, p-tau181, total-tau and NfL quantification. Group comparisons, correlations between continuous variables and ROC curve analysis were carried out to assess NfL role in discriminating between MCI due to AD and FTD, exploring the associations between NfL, ATN biomarkers and neuropsychological measures. RESULTS: NfL levels were significantly lower in the AD group, while levels of total-tau were higher. In the FTD group, significant correlations were found between NfL, p-tau181 and total-tau, and between NfL and cognitive performances. In the AD group, NfL levels were directly correlated with total-tau and p-tau181; Aß42/40 ratio was inversely correlated with total-tau and p-tau181, but not with NfL. Moreover, p-tau181 and t-tau levels were found to be associated with episodic memory and lexical-semantic impairment. Total-tau/NfL ratio differentiated prodromal-AD from FTD with an AUC of 0.951, higher than the individual measures. DISCUSSION & CONCLUSIONS: The results support that NfL and total-tau levels reflect distinct pathophysiological neurodegeneration mechanisms, independent and dependent of Aß pathology, respectively, Combining them may enhance both markers reliability, their ratio showing high accuracy in distinguishing MCI due to AD from FTD. Moreover, our results revealed associations between NfL and disease severity in FTD and between tauopathy and episodic memory and lexical-semantic impairment in prodromal-AD.
Asunto(s)
Enfermedad de Alzheimer , Demencia Frontotemporal , Enfermedad de Pick , Humanos , Demencia Frontotemporal/diagnóstico , Enfermedad de Alzheimer/diagnóstico , Filamentos Intermedios , Reproducibilidad de los Resultados , BiomarcadoresRESUMEN
Cognitive impairment is increasingly recognized to be a core feature of multiple sclerosis (MS), with important implications for the everyday life of individuals with MS and for disease management. Unfortunately, the exact mechanisms that underlie this cognitive impairment are poorly understood and there are no effective therapeutic options for this aspect of the disease. During MS, focal brain inflammatory lesions, together with pathological changes of both CNS grey matter and normal-appearing white matter, can interfere with cognitive functions. Moreover, inflammation may alter the crosstalk between the immune and the nervous systems, modulating the induction of synaptic plasticity and neurotransmission. In this Review, we examine the CNS structures and cognitive domains that are affected by the disease, with a specific focus on hippocampal involvement in MS and experimental autoimmune encephalomyelitis, an experimental model of MS. We also discuss the hypothesis that, during MS, immune-mediated alterations of synapses' ability to express long-term plastic changes may contribute to the pathogenesis of cognitive impairment by interfering with the dynamics of neuronal networks.
Asunto(s)
Sistema Nervioso Central/patología , Sistema Nervioso Central/fisiopatología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Esclerosis Múltiple/complicaciones , Sinapsis/patología , Animales , HumanosRESUMEN
BACKGROUND AND PURPOSE: After successful mechanical thrombectomy for middle cerebral artery occlusion, basal ganglia infarction is commonly detectable. Whilst the functional outcome of these patients is often good, less knowledge is available about the cognitive outcome. The aim of our study was to assess the presence of cognitive impairment within 1 week after thrombectomy. METHODS: In all, 43 subjects underwent a general cognitive assessment using the Montreal Cognitive Assessment and an extensive battery of tests. Patients were classified as cognitively impaired (CImp) or not (noCImp) according to a Montreal Cognitive Assessment score below 18. RESULTS: Cognitively impaired and noCImp subjects did not differ either in their National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at admittance, or in their Fazekas score and Alberta Stroke Program Early Computed Tomography Score. At discharge, CImp subjects showed higher scores than noCImp subjects on NIHSS (p = 0.002) and mRS (p < 0.001). The percentage of pathological performances on each neuropsychological test in the whole sample and in CImp and noCImp patients shows a similar cognitive profile between the groups. CONCLUSIONS: Some patients who underwent thrombectomy experienced a detectable cognitive impairment that probably led to worse NIHSS and mRS. The neuropsychological profile of such cognitive impairment at the acute stage consists of wide deficits in numerous cognitive domains, suggesting that basal ganglia damage may lead to complex functional impairments.
Asunto(s)
Isquemia Encefálica , Disfunción Cognitiva , Accidente Cerebrovascular , Humanos , Resultado del Tratamiento , Trombectomía/efectos adversos , Trombectomía/métodos , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infarto de la Arteria Cerebral Media/cirugía , Estudios Retrospectivos , Disfunción Cognitiva/etiología , Disfunción Cognitiva/cirugía , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/cirugíaRESUMEN
BACKGROUND AND PURPOSE: Serum levels of neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are promising neuro-axonal damage and astrocytic activation biomarkers. Susac syndrome (SS) is an increasingly recognized neurological condition and biomarkers that can help assess and monitor disease evolution are highly needed for the adequate management of these patients. sNfL and sGFAP levels were evaluated in patients with SS and their clinical relevance in the relapse and remission phase of the disease was assessed. METHODS: As part of a multicentre study that enrolled patients diagnosed with SS from six international centres, sNfL and sGFAP levels were assessed in 22 SS patients (nine during a relapse and 13 in remission) and 59 age- and sex-matched healthy controls using SimoaTM assay Neurology 2-Plex B Kit. RESULTS: Serum NfL levels were higher than those of healthy controls (p < 0.001) in SS patients and in both subgroups of patients in relapse and in remission (p < 0.001 for both), with significantly higher levels in relapse than in remission (p = 0.008). sNfL levels showed a negative correlation with time from the last relapse (r = -0.663; p = 0.001). sGFAP levels were slightly higher in the whole group of patients than in healthy controls (p = 0.046) and were more pronounced in relapse than in remission (p = 0.013). CONCLUSION: In SS patients, both sNFL and sGFAP levels increased compared with healthy controls. Both biomarkers had higher levels during clinical relapse and much lower levels in remission. sNFL was shown to be time sensitive to clinical changes and can be useful to monitor neuro-axonal damage in SS.
Asunto(s)
Esclerosis Múltiple , Síndrome de Susac , Humanos , Biomarcadores , Proteína Ácida Fibrilar de la Glía , Filamentos Intermedios/metabolismo , Esclerosis Múltiple/diagnóstico , Proteínas de Neurofilamentos , Recurrencia , Síndrome de Susac/metabolismoRESUMEN
INTRODUCTION: Status epilepticus (SE) is a frequent neurological emergency, derived from the failure of mechanisms responsible for seizure termination. The present study aims to compare the efficacy of the most common antiseizure medications (ASMs) employed for the treatment of benzodiazepine-refractory SE. METHODS: We performed a retrospective cohort study of all SE episodes treated in our hospital between January 2016 and December 2020. Inclusion criteria were: age ≥ 18 years; a diagnosis of status epilepticus. Exclusion criteria were: status epilepticus resolved by initial therapy with benzodiazepines; impossibility to retrieve medical records. We considered as effective the ASM that was the last drug introduced or increased in dose before termination of SE and without changes in the co-medication. RESULTS: A total of 244 episodes in 219 patients were included in the study. The mean age of the final study cohort was 63.6 ± 19.2, with 108 (49%) men. In the total cohort, phenytoin (PHT) showed the highest response rate (57.6%), followed by lacosamide (LCM) (40.7%) and valproate (VPA) (39.8%). The comparative efficacy among the different drugs was significantly different (p < 0.001). In the pairwise comparisons, VPA was superior to levetiracetam (LEV) (response rate: 39.75% vs 24.71%; p = 0.004), but not to LCM. Phenytoin had a significantly higher resolution rate compared to VPA (response rate: 57.63% vs 39.75%; p = 0.02) and LEV (response rate: 57.63% vs 24.71; p < 0.001). The clinical predictors of anaesthetics administration were a disorder of consciousness upon clinical presentation, previous diagnosis of epilepsy, and younger age. CONCLUSION: In our cohort of SE, PHT showed higher effectiveness in terminating established SE, as well as refractory SE in the subgroup of patients treated with anaesthetics.
Asunto(s)
Anticonvulsivantes , Estado Epiléptico , Masculino , Humanos , Adolescente , Femenino , Anticonvulsivantes/uso terapéutico , Fenitoína/uso terapéutico , Benzodiazepinas/uso terapéutico , Estudios Retrospectivos , Estudios de Cohortes , Estado Epiléptico/tratamiento farmacológico , Levetiracetam/uso terapéutico , Lacosamida/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: The Cluster Headache Impact Questionnaire (CHIQ) is a specific and easy-to-use questionnaire to assess the current impact of cluster headache (CH). The aim of this study was to validate the Italian version of the CHIQ. METHODS: We included patients diagnosed with episodic CH (eCH) or chronic CH (cCH) according to the ICHD-3 criteria and included in the "Italian Headache Registry" (RICe). The questionnaire was administered to patients through an electronic form in two sessions: at first visit for validation, and after 7 days for test-retest reliability. For internal consistency, Cronbach's alpha was calculated. Convergent validity of the CHIQ with CH features and the results of questionnaires assessing anxiety, depression, stress, and quality of life was evaluated using Spearman's correlation coefficient. RESULTS: We included 181 patients subdivided in 96 patients with active eCH, 14 with cCH, and 71 with eCH in remission. The 110 patients with either active eCH or cCH were included in the validation cohort; only 24 patients with CH were characterized by a stable attack frequency after 7 days, and were included in the test-retest cohort. Internal consistency of the CHIQ was good with a Cronbach alpha value of 0.891. The CHIQ score showed a significant positive correlation with anxiety, depression, and stress scores, while showing a significant negative correlation with quality-of-life scale scores. CONCLUSION: Our data show the validity of the Italian version of the CHIQ, which represents a suitable tool for evaluating the social and psychological impact of CH in clinical practice and research.
Asunto(s)
Cefalalgia Histamínica , Humanos , Cefalalgia Histamínica/diagnóstico , Cefalalgia Histamínica/psicología , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Italia , PsicometríaRESUMEN
l-tryptophan (Trp), an essential amino acid for mammals, is the precursor of a wide array of immunomodulatory metabolites produced by the kynurenine and serotonin pathways. The kynurenine pathway is a paramount source of several immunoregulatory metabolites, including l-kynurenine (Kyn), the main product of indoleamine 2,3-dioxygenase 1 (IDO1) that catalyzes the rate-limiting step of the pathway. In the serotonin pathway, the metabolite N-acetylserotonin (NAS) has been shown to possess antioxidant, antiinflammatory, and neuroprotective properties in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, little is known about the exact mode of action of the serotonin metabolite and the possible interplay between the 2 Trp metabolic pathways. Prompted by the discovery that NAS neuroprotective effects in EAE are abrogated in mice lacking IDO1 expression, we investigated the NAS mode of action in neuroinflammation. We found that NAS directly binds IDO1 and acts as a positive allosteric modulator (PAM) of the IDO1 enzyme in vitro and in vivo. As a result, increased Kyn will activate the ligand-activated transcription factor aryl hydrocarbon receptor and, consequently, antiinflammatory and immunoregulatory effects. Because NAS also increased IDO1 activity in peripheral blood mononuclear cells of a significant proportion of MS patients, our data may set the basis for the development of IDO1 PAMs as first-in-class drugs in autoimmune/neuroinflammatory diseases.
Asunto(s)
Encefalomielitis Autoinmune Experimental/enzimología , Encefalomielitis Autoinmune Experimental/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenasa/química , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Regulación Alostérica , Sitio Alostérico , Animales , Biocatálisis , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/genética , Femenino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Quinurenina/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Ratones Noqueados , Esclerosis Múltiple/enzimología , Esclerosis Múltiple/genética , Esclerosis Múltiple/metabolismo , Serotonina/análogos & derivados , Serotonina/química , Serotonina/metabolismo , Triptófano/metabolismoRESUMEN
BACKGROUND: Directional deep brain stimulation (DBS) leads allow a fine-tuning control of the stimulation field, however, this new technology could increase the DBS programming time because of the higher number of the possible combinations used in directional DBS than in standard nondirectional electrodes. Neuroimaging leads localization techniques and local field potentials (LFPs) recorded from DBS electrodes implanted in basal ganglia are among the most studied biomarkers for DBS programing. OBJECTIVE: This study aimed to evaluate whether intraoperative LFPs beta power and neuroimaging reconstructions correlate with contact selection in clinical programming of DBS in patients with Parkinson disease (PD). MATERIALS AND METHODS: In this retrospective study, routine intraoperative LFPs recorded from all contacts in the subthalamic nucleus (STN) of 14 patients with PD were analyzed to calculate the beta band power for each contact. Neuroimaging reconstruction obtained through Brainlab Elements Planning software detected contacts localized within the STN. Clinical DBS programming contact scheme data were collected after one year from the implant. Statistical analysis evaluated the diagnostic performance of LFPs beta band power and neuroimaging data for identification of the contacts selected with clinical programming. We evaluated whether the most effective contacts identified based on the clinical response after one year from implant were also those with the highest level of beta activity and localized within the STN in neuroimaging reconstruction. RESULTS: LFPs beta power showed a sensitivity of 67%, a negative predictive value (NPV) of 84%, a diagnostic odds ratio (DOR) of 2.7 in predicting the most effective contacts as evaluated through the clinical response. Neuroimaging reconstructions showed a sensitivity of 62%, a NPV of 77%, a DOR of 1.20 for contact effectivity prediction. The combined use of the two methods showed a sensitivity of 87%, a NPV of 87%, a DOR of 2.7 for predicting the clinically more effective contacts. CONCLUSIONS: The combined use of LFPs beta power and neuroimaging localization and segmentations predict which are the most effective contacts as selected on the basis of clinical programming after one year from implant of DBS. The use of predictors in contact selection could guide clinical programming and reduce time needed for it.