Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 14 de 14
Filter
1.
Frontiers in neurology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1970781

ABSTRACT

Cancer immunotherapy represents a novel anticancer strategy that acts directly on the immune system, promoting its activation toward cancer cells to enhance its natural ability to fight cancer. Among various treatments currently used or investigated, chimeric antigen receptors (CAR) T-cell therapy and immune checkpoint inhibitors (ICIs) have consistently proven their efficacy. These innovations are progressively improving the standard of care in cancer treatment, yet they are hampered by novel neurological adverse events, attributing to neurologists a key role in the multidisciplinary oncological team. Indeed, neurotoxicity may develop in up to 77% of patients who received CAR T-cell therapy and usually presents with encephalopathy characterized by a predominant frontal lobe dysfunction. This neurotoxicity is related to cytokine release syndrome, a systemic hyperinflammatory condition triggered by CAR T-cells. On the other hand, following treatment with ICIs, unrestrained T-cells may lead to central and peripheral neurological disorders by antigen-directed autoimmunity. Notably, biological and clinical similarities have been underlined between neurotoxicity related to CAR T-cell therapy and neurological manifestations of cytokine storms (e.g. COVID-19-related encephalopathy), as well as between a subgroup of ICI-related neurological adverse events and paraneoplastic neurological syndromes. Therefore, these cancer immunotherapy-related neurological syndromes may provide an unprecedented, perhaps transitory, opportunity to shed light on the underlying pathogenic mechanisms of a wide spectrum of neurological syndromes and to push forward our knowledge in neuroimmunology.

2.
Epilepsia ; 63(9): 2279-2289, 2022 09.
Article in English | MEDLINE | ID: covidwho-1916134

ABSTRACT

OBJECTIVE: Data on COVID-19 outcomes in persons with epilepsy (PWE) are scarce and inconclusive. We aimed to study the risk of hospitalization and death for COVID-19 in a large cohort of PWE from March 1, 2020 to October 31, 2021. METHODS: The historical cohort design (EpiLink Bologna) compared adult PWE grouped into people with focal epilepsy (PFE), idiopathic generalized epilepsy (PIGE), and developmental and/or epileptic encephalopathy (PDEE), and a population cohort matched (ratio 1:10) for age, sex, residence, and comorbidity (assessed with the multisource comorbidity score), living in the local health trust of Bologna (approximately 800 000 residents). Clinical data were linked to health administrative data. RESULTS: In both cohorts (EpiLink: n = 1575 subjects, 1128 PFE, 267 PIGE, 148 PDEE, 32 other; controls: n = 15 326 subjects), 52% were females, and the mean age was 50 years (SD = 18). Hospital admissions for COVID-19 in the whole period were 49 (3.1%) in PWE and 225 (1.5%) in controls. The adjusted hazard ratio (aHR) in PWE was 1.9 (95% confidence interval [CI] = 1.4-2.7). The subgroups at higher risk were PFE (aHR = 1.9, 95% CI = 1.3-2.8) and PDEE (aHR = 3.9, 95% CI = 1.7-8.7), whereas PIGE had a risk comparable to the controls (aHR = 1.1, 95% CI = .3-3.5). Stratified analyses of the two main epidemic waves (March-May 2020, October 2020-May 2021) disclosed a higher risk of COVID-19-related hospitalization during the first epidemic wave (March-May 2020; aHR = 3.8, 95% CI = 2.2-6.7). Polytherapy with antiseizure medications contributed to a higher risk of hospital admission. Thirty-day risk of death after hospitalization was 14% in both PWE and controls. SIGNIFICANCE: During the first 20 months since the outbreak of COVID-19 in Bologna, PWE had a doubled risk of COVID-19 hospital admission compared to a matched control population. Conversely, epilepsy did not represent a risk factor for COVID-19-related death.


Subject(s)
COVID-19 , Epilepsy , Adult , COVID-19/epidemiology , Cohort Studies , Comorbidity , Epilepsy/epidemiology , Female , Hospitalization , Humans , Male , Middle Aged
7.
Ann Clin Transl Neurol ; 8(4): 968-979, 2021 04.
Article in English | MEDLINE | ID: covidwho-1155205

ABSTRACT

OBJECTIVE: Many neurological manifestations are associated with COVID-19, including a distinct form of encephalopathy related to cytokine storm, the acute systemic inflammatory syndrome present in a subgroup of COVID-19 patients. Cytokine storm is also associated with immune effector cell-associated neurotoxicity syndrome (ICANS), a complication of chimeric antigen receptor T-cell (CAR-T) therapy, a highly effective treatment for refractory hematological malignancies. We investigated whether COVID-19-related encephalopathy, ICANS, and other encephalopathies associated with cytokine storm, share clinical and investigative findings. METHODS: Narrative literature review. RESULTS: Comparisons between COVID-19-related encephalopathy and ICANS revealed several overlapping features. Clinically, these included dysexecutive syndrome, language disturbances, akinetic mutism and delirium. EEG showed a prevalence of frontal abnormalities. Brain MRI was often unrevealing. CSF elevated cytokine levels have been reported. A direct correlation between cytokine storm intensity and severity of neurological manifestations has been shown for both conditions. Clinical recovery occurred spontaneously or following immunotherapies in most of the patients. Similar clinical and investigative features were also reported in other encephalopathies associated with cytokine storm, such as hemophagocytic lymphohistiocytosis, sepsis, and febrile infection-associated encephalopathies. INTERPRETATION: COVID-19-related encephalopathy and ICANS are characterized by a predominant electro-clinical frontal lobe dysfunction and share several features with other encephalopathies associated with cytokine storm, which may represent the common denominator of a clinical spectrum of neurological disorders. Therefore, we propose a unifying definition of cytokine storm-associated encephalopathy (CySE), and its diagnostic criteria.


Subject(s)
Brain Diseases/physiopathology , Brain/physiopathology , COVID-19/physiopathology , Cytokine Release Syndrome/physiopathology , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen , Brain Diseases/epidemiology , Brain Diseases/therapy , COVID-19/epidemiology , COVID-19/therapy , Cytokine Release Syndrome/epidemiology , Cytokine Release Syndrome/therapy , Humans , Immunotherapy, Adoptive/trends
8.
Front Neurol ; 11: 613719, 2020.
Article in English | MEDLINE | ID: covidwho-1006010

ABSTRACT

Objectives: We explored the impact of the coronavirus disease-19 (COVID-19) emergency on the health of people with epilepsy (PwE). We also investigated their attitude toward telemedicine. Methods: The PubMed database up to September 10, 2020 was searched for questionnaire-based studies conducted in PwE during the COVID-19 emergency, and the literature retrieved was reviewed. In addition, all patients who had a telephone consultation with our center between May 7 and July 31, 2020 were invited to fill in a 57-item online questionnaire focusing on epilepsy and comorbidities, any changes in lifestyle or clinical conditions and any emergency-related problems arising during the COVID-19 emergency, and their views on telemedicine. Associations between variables were detected through X 2 test and Fisher's exact test. Univariate and multivariate logistic regression models were used to evaluate the effects of different factors on clinical conditions. Results: Twelve studies met the literature search criteria. They showed that the rate of seizure worsening during the emergency ranged from 4 to 35% and was mainly correlated with epilepsy severity, sleep disturbances and COVID-19-related issues. Our questionnaire was filled in by 222 PwE or caregivers. One hundred (76.6%) reported unchanged clinical conditions, 25 (11.3%) an improvement, and 27 (12%) a deterioration. Reported clinical worsening was associated with a psychiatric condition and/or medication (OR = 12.59, p < 0.001), sleep disorders (OR = 8.41, p = 0.001), limited access to healthcare (OR = 4.71, p = 0.016), and experiencing seizures during the emergency (OR = 4.51, p = 0.007). Telemedicine was considered acceptable by 116 subjects (52.3%). Conclusions: Most PwE did not experience a significant change in their clinical conditions during the COVID-19 emergency. However, severity of epilepsy, concomitant disability, comorbid psychiatric conditions, sleep disorders and limited access to healthcare may affect their health.

9.
Front Neurol ; 11: 587226, 2020.
Article in English | MEDLINE | ID: covidwho-914438

ABSTRACT

Introduction: Neurological manifestations are emerging as relatively frequent complications of corona virus disease 2019 (COVID-19), including stroke and encephalopathy. Clinical characteristics of the latter are heterogeneous and not yet fully elucidated, while the pathogenesis appears related to neuroinflammation in a subset of patients. Case: A middle-aged man presented with acute language disturbance at the emergency department. Examination revealed expressive aphasia, mild ideomotor slowing, and severe hypocapnic hypoxemia. Multimodal CT assessment and electroencephalogram (EEG) did not reveal any abnormalities. COVID-19 was diagnosed based on chest CT findings and positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription PCR (RT-PCR) on nasopharyngeal swab. The following day, neurological symptoms progressed to agitated delirium and respiratory status worsened, requiring admission to the ICU and mechanical ventilation. Brain MRI and cerebrospinal fluid (CSF) studies were unremarkable. RT-PCR for SARS-CoV-2 on CSF was negative. He received supportive treatment and intravenous low-dose steroids. His neurological and respiratory status resolved completely within 2 weeks. Conclusions: We report a patient with reversible COVID-19-related encephalopathy presenting as acute aphasia, mimicking stroke or status epilepticus, eventually evolving into delirium. Although large-vessel stroke is frequently encountered in COVID-19, our case suggests that focal neurological deficits may occur as the earliest feature of encephalopathy. Neurological status reversibility and the absence of abnormalities on brain MRI are consistent with a functional rather than a structural neuronal network impairment.

10.
J Neurol ; 268(8): 2671-2675, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-841658

ABSTRACT

OBJECTIVE: To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy. METHODS: We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg. RESULTS: Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19-55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1-10 days). No adverse events related to IVIg were observed. CONCLUSIONS: Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.


Subject(s)
Brain Diseases , COVID-19 , Aged , Brain Diseases/drug therapy , Female , Humans , Immunoglobulins, Intravenous , Retrospective Studies , SARS-CoV-2
11.
J Neuroimmunol ; 349: 577400, 2020 12 15.
Article in English | MEDLINE | ID: covidwho-792960

ABSTRACT

Encephalopathy is emerging as a recurrent complication of COVID-19 yet remains poorly characterized. We report the case of a middle-aged woman with COVID-19-related encephalopathy presenting as expressive aphasia and inattentiveness, subsequently progressing to agitation and marked confusion. Brain MRI and CSF analysis were unremarkable, while EEG showed slowing with frontal sharp waves. Neuropsychiatric symptoms resolved following treatment with tocilizumab. CNS involvement in COVID-19 may present as a subacute encephalopathy characterized by prominent frontal lobe dysfunction, with language disturbances as first neurological manifestation. Future studies should further investigate the role of tocilizumab in treating COVID-19-related encephalopathy.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Aphasia/etiology , Brain Diseases/virology , COVID-19/complications , Cytokine Release Syndrome/drug therapy , Brain Diseases/drug therapy , Brain Diseases/immunology , COVID-19/drug therapy , COVID-19/immunology , Cytokine Release Syndrome/virology , Female , Humans , Middle Aged , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL