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1.
Comput Biol Med ; 139: 104997, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34753079

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI)-based morphometry and relaxometry are proven methods for the structural assessment of the human brain in several neurological disorders. These procedures are generally based on T1-weighted (T1w) and/or T2-weighted (T2w) MRI scans, and rigid and affine registrations to a standard template(s) are essential steps in such studies. Therefore, a fully automatic quality control (QC) of these registrations is necessary in big data scenarios to ensure that they are suitable for subsequent processing. METHOD: A supervised machine learning (ML) framework is proposed by computing similarity metrics such as normalized cross-correlation, normalized mutual information, and correlation ratio locally. We have used these as candidate features for cross-validation and testing of different ML classifiers. For 5-fold repeated stratified grid search cross-validation, 400 correctly aligned, 2000 randomly generated misaligned images were used from the human connectome project young adult (HCP-YA) dataset. To test the cross-validated models, the datasets from autism brain imaging data exchange (ABIDE I) and information eXtraction from images (IXI) were used. RESULTS: The ensemble classifiers, random forest, and AdaBoost yielded best performance with F1-scores, balanced accuracies, and Matthews correlation coefficients in the range of 0.95-1.00 during cross-validation. The predictive accuracies reached 0.99 on the Test set #1 (ABIDE I), 0.99 without and 0.96 with noise on Test set #2 (IXI, stratified w.r.t scanner vendor and field strength). CONCLUSIONS: The cross-validated and tested ML models could be used for QC of both T1w and T2w rigid and affine registrations in large-scale MRI studies.

2.
Int J Infect Dis ; 112: 327-329, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34600133

RESUMO

This article reports a fatal case of human herpesvirus 6 (HHV-6) myelitis following CD19-targeted chimeric antigen receptor T-cell therapy. Infection from HHV-6 reactivation after haematopoietic stem cell transplant is established, and outside of this population is limited to case reports. The patient developed cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome that responded to corticosteroids both clinically and on imaging. Subsequently, ascending flaccid paralysis developed, leading to neuromuscular respiratory failure and, ultimately, death. Disease progression was refractory to foscarnet and multiple immunomodulating agents. HHV-6 should be considered in patients with encephalitis and myelitis after adoptive T-cell therapy.

3.
Blood Adv ; 5(14): 2799-2806, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34264268

RESUMO

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Síndrome da Liberação de Citocina , Ferritinas , Humanos
4.
J Neurooncol ; 153(3): 441-446, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34076832

RESUMO

INTRODUCTION: Paraneoplastic cerebellar degeneration (PCD) is a rare set of neurological disorders arising from tumor-associated autoimmunity against antigens within the cerebellum. Anti-Purkinje cell cytoplasmic antibody 1 (PCA-1), or anti-Yo, is the most commonly linked antibody and is classically associated with breast and ovarian cancers. METHODS: Medical records of patients at our institution who developed PCA-1 associated PCD were reviewed. Clinical information, including cancer history, cancer-directed treatment, and serum and CSF titers of PCA-1 antibody were extracted. CASES: We report a series of cases of PCA-1 associated PCD in patients with known breast or ovarian cancer diagnosis not receiving immunotherapy. These cases highlight aspects of PCA-1 paraneoplastic syndrome such as triggering by cytotoxic chemotherapy or surgery, the possibility of tumor recurrence and the association with development of a second cancer. DISCUSSION: Diagnosis of the syndrome requires neurological workup with lumbar puncture (LP) with cerebrospinal fluids (CSF) studies, serum and CSF paraneoplastic antibody panel, and neuroimaging. Inpatient admission for prompt workup and initiation of treatment is recommended. Treatment most commonly includes immunosuppression with corticosteroids, plasmapheresis, and/or intravenous immune globulin (IVIG); however, we postulate that other immune modulating treatments may warrant consideration. CONCLUSION: These cases highlight the need for early recognition of the syndrome in patients receiving nonimmune based chemotherapy, for prompt workup and treatment.

5.
J Neural Eng ; 18(4)2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33836520

RESUMO

Objective.Somatosensory evoked potentials (SSEPs) recorded with electrocorticography (ECoG) for central sulcus (CS) identification is a widely accepted procedure in routine intraoperative neurophysiological monitoring. Clinical practices test the short-latency SSEPs for the phase reversal over strip electrodes. However, assessments based on waveform morphology are susceptible to variations in interpretations due to the hand area's localized nature and usually require multiple electrode placements or electrode relocation. We investigated the feasibility of unsupervised delineation of the CS by using the spatiotemporal patterns of the SSEP captured with the ECoG grid.Approach. Intraoperatively, SSEPs were recorded from eight patients using ECoG grids placed over the sensorimotor cortex. Neurosurgeons blinded to the electrophysiology identified the sensory and motor gyri using neuronavigation based on sulcal anatomy. We quantified the most discriminatory time points in SSEPs temporal profile between the primary motor (M1) and somatosensory (S1) cortex using the Fisher discrimination criterion. We visualized the amplitude gradient of the SSEP over a 2D heat map to provide visual feedback for the delineation of the CS based on electrophysiology. Subsequently, we employed spectral clustering using the entire the SSEP waveform without selecting any time points and grouped ECoG channels in an unsupervised fashion.Main results.Consistently in all patients, two different time points provided almost equal discrimination between anterior and posterior channels, which vividly outlined the CS when we viewed the SSEP amplitude distribution as a spatial 2D heat map. The first discriminative time point was in proximity to the conventionally favored ∼20 ms peak (N20), and the second time point was slightly later than the markedly high ∼30 ms peak (P30). Still, the location of these time points varied noticeably across subjects. Unsupervised clustering approach separated the anterior and posterior channels with an accuracy of 96.3% based on the time derivative of the SSEP trace without the need for a subject-specific time point selection. In contrast, the raw trace resulted in an accuracy of 88.0%.Significance. We show that the unsupervised clustering of the SSEP trace assessed with subdural electrode grids can delineate the CS automatically with high precision, and the constructed heat maps can localize the motor cortex. We anticipate that the spatiotemporal patterns of SSEP fused with machine learning can serve as a useful tool to assist in surgical planning.


Assuntos
Monitorização Neurofisiológica Intraoperatória , Córtex Motor , Potenciais Somatossensoriais Evocados , Mãos , Humanos , Aprendizado de Máquina não Supervisionado
6.
Arthritis Rheumatol ; 73(8): 1564, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33682370
8.
Arthritis Rheumatol ; 73(5): 866-874, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33258544

RESUMO

OBJECTIVE: To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes. METHODS: We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available. RESULTS: A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received ≥1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICI-myositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection. CONCLUSION: ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined.


Assuntos
Inibidores de Checkpoint Imunológico/efeitos adversos , Miastenia Gravis/induzido quimicamente , Miocardite/induzido quimicamente , Miosite/induzido quimicamente , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Infecções/epidemiologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/epidemiologia , Miastenia Gravis/mortalidade , Miocardite/epidemiologia , Miocardite/mortalidade , Miosite/epidemiologia , Miosite/mortalidade , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/etiologia , Estudos Retrospectivos
9.
Ann Med Surg (Lond) ; 60: 81-86, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33133590

RESUMO

Background: To study the clinical, radiological, electroencephalographic, and cerebrospinal fluid (CSF) features of Human Herpes Virus 6 (HHV-6) encephalitis in leukemia patients underwent allogeneic hematopoietic stem cell transplantation (HSCT). Methods: We retrospectively reviewed all leukemia patients who underwent allogeneic HSCT between January 2010 and December 2018. The clinical, radiological, electroencephalographic, and CSF features of those with HHV6 encephalitis were recorded. Results: A total of five cases of HHV6 encephalitis were identified. Three patients had Chronic Myelogenous Leukemia, one had Chronic Lymphocytic Leukemia and one had Acute Lymphoblastic Leukemia. All of them presented a few months after transplantation with altered mental status. Comorbidities included pancytopenia, sepsis, graft versus host disease, and multi-organ failure. EEG showed focal seizures originating from temporal lobes in two patients, generalized or focal periodic discharges in three patients, focal slowing in two patients, and diffuse slowing in three patients. MRI brain showed T2/FLAIR hyper-intensities in four patients; two of them in bilateral temporal lobes, one in the thalamus/hypothalamus/brainstem/cerebellum/basal ganglia, and one in the periventricular areas. CSF showed pleocytosis, high protein, and positive HHV-6 PCR. Foscarnet was used as an anti-viral agent. Anti-epileptics used were phenytoin, levetiracetam, and valproic acid. Four patients died in a few months, whereas one recovered completely. Conclusions: HHV-6 encephalitis can add significant morbidity and mortality to leukemic patients following allogeneic HSCT. Patients present with typical clinical features of encephalitis. Salient EEG characteristics include periodic discharges or overt temporal lobe seizures. MRI findings are T2/FLAIR signal hyperintensities, mainly in the temporal lobes.

10.
Palliat Support Care ; 18(5): 609-613, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040773

RESUMO

OBJECTIVE: B vitamins are essential for the functioning of the nervous system. Vitamin B1 (thiamine) deficiency is associated with neuropsychiatric syndromes such as Wernicke's encephalopathy (WE), which, if untreated, has an estimated mortality of 17-20%. Although the prevalence of thiamine deficiency in the general population is difficult to estimate, it is being increasingly recognized in oncology, especially in the inpatient setting. We describe three cases of thiamine deficiency (TD) in the outpatient psychiatric oncology setting. METHOD: Retrospective chart review of three adult patients, who were seen in the psychiatric oncology clinic and found to have TD on laboratory testing, was done. Patient, disease, and thiamine treatment-related information were obtained, and descriptive statistics were used to analyze the data. RESULTS: The average age was 59 years, mean body mass index (BMI) was 22.00 ± 4.58 (mean ± SD), and mean thiamine level was 59.10 ± 7.69 that ranged from 45 to 68 nmol/L (normal thiamine level reference: 70-180 nmol/L). None of the patients had brain imaging nor cerebrospinal fluid analysis. Risk factors such as unbalanced nutrition, prior GI surgery, renal disease, and chemotherapy were noted. SIGNIFICANCE OF RESULTS: TD can have a multifactorial etiology in oncology. Identification of TD in both inpatient and outpatient setting is important. Our report highlights how early identification of TD in the outpatient setting can help prevent further clinical progression.


Assuntos
Oncologia/métodos , Serviços de Saúde Mental/estatística & dados numéricos , Deficiência de Tiamina/complicações , Idoso , Instituições de Assistência Ambulatorial/organização & administração , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Índice de Massa Corporal , Feminino , Humanos , Masculino , Oncologia/estatística & dados numéricos , Transtornos Mentais/psicologia , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Prevalência , Estudos Retrospectivos , Fatores de Risco , Deficiência de Tiamina/psicologia
11.
Blood Adv ; 4(16): 3943-3951, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32822484

RESUMO

Neurotoxicity or immune effector cell-associated neurotoxicity syndrome (ICANS) is the second most common acute toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, there are limited data on the clinical and radiologic correlates of ICANS. We conducted a cohort analysis of 100 consecutive patients with relapsed or refractory large B-cell lymphoma (LBCL) treated with standard of care axicabtagene ciloleucel (axi-cel). ICANS was graded according to an objective grading system. Neuroimaging studies and electroencephalograms (EEGs) were reviewed by an expert neuroradiologist and neurologist. Of 100 patients included in the study, 68 (68%) developed ICANS of any grade and 41 (41%) had grade ≥3. Median time to ICANS onset was 5 days, and median duration was 6 days. ICANS grade ≥3 was associated with high peak ferritin (P = .03) and C-reactive protein (P = .001) levels and a low peak monocyte count (P = .001) within the 30 days after axi-cel infusion. Magnetic resonance imaging was performed in 38 patients with ICANS and revealed 4 imaging patterns with features of encephalitis (n = 7), stroke (n = 3), leptomeningeal disease (n = 2), and posterior reversible encephalopathy syndrome (n = 2). Abnormalities noted on EEG included diffuse slowing (n = 49), epileptiform discharges (n = 6), and nonconvulsive status epilepticus (n = 8). Although reversible, grade ≥3 ICANS was associated with significantly shorter progression-free (P = .02) and overall survival (progression being the most common cause of death; P = .001). Our results suggest that imaging and EEG abnormalities are common in patients with ICANS, and high-grade ICANS is associated with worse outcome after CAR T-cell therapy in LBCL patients.


Assuntos
Síndromes Neurotóxicas , Síndrome da Leucoencefalopatia Posterior , Antígenos CD19/uso terapêutico , Humanos , Imunoterapia Adotiva , Síndromes Neurotóxicas/diagnóstico por imagem , Síndromes Neurotóxicas/etiologia
12.
Curr Neurol Neurosci Rep ; 20(7): 27, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32514633

RESUMO

PURPOSE OF REVIEW: This review provides clinical characterization and approach to management of neurotoxicities associated with checkpoint inhibitor therapy and chimeric antigen receptor T cell (CAR T cell) therapy. RECENT FINDINGS: Immuno-oncology has revolutionized cancer treatment. The immunomodulatory effect of these treatments extends beyond the targeted cancers; however, with a range of immune-mediated toxicities being associated with these therapies. Both the peripheral and central nervous system are vulnerable to these toxicities, with several distinct clinical syndromes strongly associated with specific immunotherapies. Neurologic immune-related adverse events are significant sequelae of both checkpoint inhibitors and CAR T cell therapy. In addition to clinical characterization of these syndromes, an understanding of the biologic underpinnings of these sequelae is essential. This will facilitate identification of patients at risk of these toxicities, develop treatments to prevent them and identify more effective clinical treatment when they occur.


Assuntos
Neoplasias , Síndromes Neurotóxicas , Humanos , Imunoterapia/efeitos adversos , Neoplasias/terapia
13.
Front Neurosci ; 14: 100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116533

RESUMO

It is well-known that motor cortical oscillatory components are modulated in their amplitude during voluntary and imagined movements. These patterns have been used to develop brain-machine interfaces (BMI) which focused mostly on movement kinematics. In contrast, there have been only a few studies on the relation between brain oscillatory activity and the control of force, in particular, grasping force, which is of primary importance for common daily activities. In this study, we recorded intraoperative high-density electrocorticography (ECoG) from the sensorimotor cortex of four patients while they executed a voluntary isometric hand grasp following verbal instruction. The grasp was held for 2 to 3 s before being instructed to relax. We studied the power modulations of neural oscillations during the whole time-course of the grasp (onset, hold, and offset phases). Phasic event-related desynchronization (ERD) in the low-frequency band (LFB) from 8 to 32 Hz and event-related synchronization (ERS) in the high-frequency band (HFB) from 60 to 200 Hz were observed at grasp onset and offset. However, during the grasp holding period, the magnitude of LFB-ERD and HFB-ERS decreased near or at the baseline level. Overall, LFB-ERD and HFB-ERS show phasic characteristics related to the changes of grasp force (onset/offset) in all four patients. More precisely, the fluctuations of HFB-ERS primarily, and of LFB-ERD to a lesser extent, correlated with the time-course of the first time-derivative of force (yank), rather than with force itself. To the best of our knowledge, this is the first study that establishes such a correlation. These results have fundamental implications for the decoding of grasp in brain oscillatory activity-based neuroprosthetics.

14.
J Immunother Cancer ; 7(1): 319, 2019 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-31753014

RESUMO

BACKGROUND: Myasthenia gravis (MG) is a rare but life-threatening adverse event of immune checkpoint inhibitors (ICI). Given the limited evidence, data from a large cohort of patients is needed to aid in recognition and management of this fatal complication. METHODS: We reviewed our institutional databases to identify patients who had cancer and MG in the setting of ICI. We systematically reviewed the literature through August 2018 to identify all similar reported patients. We collected data on clinical and diagnostic features, management, and outcomes of these cases. RESULTS: Sixty-five patients were identified. Median age was 73 years; 42 (65%) were males, 31 (48%) had metastatic melanoma, and 13 (20%) had a preexisting MG before ICI initiation. Most patients received anti-PD-1 (82%). Sixty-three patients (97%) developed ICI-related MG (new onset or disease flare) after a median of 4 weeks (1 to 16 weeks) of ICI initiation. Twenty-four patients (37%) experienced concurrent myositis, and respiratory failure occurred in 29 (45%). ICI was discontinued in 61 patients (97%). Death was reported in 24 patients (38%); 15 (23%) due to MG complication. A better outcome was observed in patients who received intravenous immunoglobulin (IVIG) or plasmapheresis (PLEX) as first-line therapy than in those who received steroids alone (95% vs 63% improvement of MG symptoms, p = 0.011). CONCLUSIONS: MG is a life-threatening adverse event of acute onset and rapid progression after ICI initiation. Early use of IVIG or PLEX, regardless of initial symptoms severity, may lead to better outcomes than steroids alone. Our data suggest the need to reassess the current recommendations for management of ICI-related MG until prospective longitudinal studies are conducted to establish the ideal management approach for these patients.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Miastenia Gravis/etiologia , Neoplasias/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/efeitos adversos , Miastenia Gravis/diagnóstico , Miastenia Gravis/epidemiologia , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Avaliação de Sintomas
15.
Artigo em Inglês | MEDLINE | ID: mdl-31659724

RESUMO

INTRODUCTION: Preserving the integrity of the corticospinal tract (CST) while maximizing the extent of tumor resection is one of the key principles of brain tumor surgery to prevent new neurologic deficits. Our goal was to determine the impact of the use of perioperative diffusion tensor imaging (DTI) fiber-tracking protocols for location of the CSTs, in conjunction with intraoperative direct electrical stimulation (DES) on patient neurologic outcomes. The role of combining DES and CST shift in intraoperative magnetic resonance imaging (iMRI) to enhance extent of resection (EOR) has not been studied previously. METHODS: A total of 53 patients underwent resection of tumors adjacent to the motor gyrus and the underlying CST between June 5, 2009, and April 16, 2013. All cases were performed in the iMRI (BrainSuite 1.5 T). Preoperative DTI mapping and intraoperative cortical and subcortical DES including postoperative DTI mapping were performed in all patients. There were 32 men and 21 women with 40 high-grade gliomas (76%), 4 low-grade gliomas (8%), and 9 (17%) metastases. Thirty-four patients (64%) were newly diagnosed, and 19 (36%) had a previous resection. There were 31 (59%) right-sided and 22 (42%) left-sided tumors. Eighteen patients (34%) had a re-resection after the first intraoperative scan. Most patients had motor-only mapping, and one patient had both speech and motor mapping. Relative to the resection margin, the CST after the first iMRI was designated as having an outward shift (OS), inward shift (IS), or no shift (NS). RESULTS: A gross total resection (GTR) was achieved in 41 patients (77%), subtotal resection in 4 (7.5%), and a partial resection in 8 (15%). Eighteen patients had a re-resection, and the mean EOR increased from 84% to 95% (p = 0.002). Of the 18 patients, 7 had an IS, 8 an OS, and in 3 NS was noted. More patients in the OS group had a GTR compared with the IS or NS groups (p = 0.004). Patients were divided into four groups based on the proximity of the tumor to the CST as measured from the preoperative scan. Group 1 (32%) included patients whose tumors were 0 to 5 mm from the CST based on preoperative scans; group 2 (28%), 6 to 10 mm; group 3 (13%), 11 to 15 mm; and group 4 (26%), 16 to 20 mm, respectively. Patients in group 4 had fewer neurologic complications compared with other groups at 1 and 3 months postoperatively (p = 0.001 and p = 0.007, respectively) despite achieving a similar degree of resection (p = 0.61). Furthermore, the current of intraoperative DES was correlated to the distance of the tumor to the CST, and the regression equation showed a close linear relationship between the two parameters. CONCLUSIONS: Combining information about intraoperative CST and DES in the iMRI can enhance resection in brain tumors (77% had a GTR). The relative relationship between the positions of the CST to the resection cavity can be a dynamic process that could further influence the surgeon's decision about the stimulation parameters and EOR. Also, the patients with an OS of the CST relative to the resection cavity had a GTR comparable with the other groups.

16.
J Intensive Care ; 7: 62, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31890224

RESUMO

Background: Non-convulsive status epilepticus (NCSE) is present in 10-30% of ICU patients with altered mental status (AMS) and is associated to poor outcomes. To our knowledge, there is no data describing the prevalence and outcomes of critically ill cancer patients with AMS associated to non-convulsive seizures (NCS) or NCSE. We aim to describe the outcomes and risk factors of critically ill cancer patients with encephalopathy associated with non-convulsive seizures (NCS). Methods: This is a 3-year prospective observational study in a mixed oncological ICU at MD Anderson Cancer Center. Data of ICU patients with moderate to severe encephalopathy (Glasgow Coma Score < 13) that underwent EEG monitoring to rule out NCS were collected. Multivariate logistic regression was performed to identify risk factors and outcomes. Results: Of the 317 patients with encephalopathy who underwent EEG monitoring, 14.5% had NCS. Known risk factors such as sepsis, CNS infection, antibiotics, and cardiac arrest were not associated with increased risk of NCS. Patients with NCS were more likely to have received recent chemotherapy (41.3% vs 21.4%; p = 0.0036), have a CNS disease (39% vs 24.4%; p = 0.035), and abnormal brain imaging (60.9% vs 44.6%; p = 0.041). Patients with lower SOFA scores, normal renal function, and absence of shock were likely to have NCS as the cause of their encephalopathy (p < 0.03). After multivariate analysis, only abnormal brain imaging and absence of renal failure were associated with NCS. Mortality was significantly lower in patients with non-convulsive seizures when compared to those without seizures (45.7% vs 64%; p = 0.022); however, there was no significant association of seizures and mortality on a multivariable logistic regression analysis. Conclusions: NCS in critically ill cancer patients is associated with abnormalities on brain imaging and lower prevalence of organ failure. Diagnosis and treatment of NCS should be a priority in encephalopathic cancer patients, as they can have lower mortality than non-seizing patients. Opposite to other populations, NCS should not be considered a poor prognostic factor in critically ill encephalopathic cancer patients as they reflect a reversible cause for altered mentation.

17.
N Engl J Med ; 379(15): 1443-1451, 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30304652

RESUMO

JC virus, the cause of progressive multifocal leukoencephalopathy (PML), and the BK virus are genetically similar and share sequence homology in immunogenic proteins. We treated three immunosuppressed patients with PML with ex vivo-expanded, partially HLA-matched, third-party-produced, cryopreserved BK virus-specific T cells. The immunosuppression in these patients was due to the conditioning regimen for cord-blood transplantation in one patient, a myeloproliferative neoplasm treated with ruxolitinib in another, and acquired immunodeficiency syndrome in the third. After T-cell infusion in two of the patients, alleviation of the clinical signs and imaging features of PML was seen and JC virus in the cerebrospinal fluid (CSF) cleared. The other patient had a reduction in JC viral load and stabilization of symptoms that persisted until her death 8 months after the first infusion. Two of the patients had immune reconstitution syndrome. Donor-derived T cells were detected in the CSF after infusion. (Funded by the M.D. Anderson Cancer Center Moon Shots Program and the National Institutes of Health; ClinicalTrials.gov number, NCT02479698 .).


Assuntos
Vírus BK/imunologia , Terapia Baseada em Transplante de Células e Tecidos , Leucoencefalopatia Multifocal Progressiva/terapia , Linfócitos T/transplante , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Feminino , Humanos , Síndrome Inflamatória da Reconstituição Imune , Hospedeiro Imunocomprometido , Infusões Parenterais , Vírus JC , Leucoencefalopatia Multifocal Progressiva/diagnóstico por imagem , Leucoencefalopatia Multifocal Progressiva/virologia , Imageamento por Ressonância Magnética , Masculino , Linfócitos T/imunologia , Transplante Homólogo , Carga Viral
18.
SAGE Open Med Case Rep ; 6: 2050313X18792422, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30116528

RESUMO

Atezolizumab is a monoclonal antibody that targets programmed death ligand-1. Treatments with this drug may cause immune-related adverse events by creating an exaggerated inflammatory response. The most common side effects are fatigue, rash, and gastrointestinal symptoms. Cases of central nervous system toxicity such as encephalitis and encephalopathy are uncommon. We present the case of a 53-year-old female with metastatic squamous cell carcinoma of the cervix who presented to the emergency room 13 days after receiving atezolizumab with altered mental status, headache, and meningeal signs. She was admitted to the intensive care unit. Infectious, anatomical, and neoplastic etiologies were ruled out. Auto-immune meningoencephalitis was diagnosed and treated with high-dose steroids. Within 10 days of the diagnosis, she had clinical, radiological, and laboratory improvement. Given the increasing use of novel immunotherapies and life-threatening side effects associated with them, healthcare providers in the intensive care unit should be aware of their diagnosis and management.

19.
Brain ; 141(3): 713-730, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29394328

RESUMO

High-frequency oscillations in local field potentials recorded with intracranial EEG are putative biomarkers of seizure onset zones in epileptic brain. However, localized 80-500 Hz oscillations can also be recorded from normal and non-epileptic cerebral structures. When defined only by rate or frequency, physiological high-frequency oscillations are indistinguishable from pathological ones, which limit their application in epilepsy presurgical planning. We hypothesized that pathological high-frequency oscillations occur in a repetitive fashion with a similar waveform morphology that specifically indicates seizure onset zones. We investigated the waveform patterns of automatically detected high-frequency oscillations in 13 epilepsy patients and five control subjects, with an average of 73 subdural and intracerebral electrodes recorded per patient. The repetitive oscillatory waveforms were identified by using a pipeline of unsupervised machine learning techniques and were then correlated with independently clinician-defined seizure onset zones. Consistently in all patients, the stereotypical high-frequency oscillations with the highest degree of waveform similarity were localized within the seizure onset zones only, whereas the channels generating high-frequency oscillations embedded in random waveforms were found in the functional regions independent from the epileptogenic locations. The repetitive waveform pattern was more evident in fast ripples compared to ripples, suggesting a potential association between waveform repetition and the underlying pathological network. Our findings provided a new tool for the interpretation of pathological high-frequency oscillations that can be efficiently applied to distinguish seizure onset zones from functionally important sites, which is a critical step towards the translation of these signature events into valid clinical biomarkers.awx374media15721572971001.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/fisiopatologia , Epilepsias Parciais/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Eletrodos Implantados , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Periodicidade
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