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INTRODUCTION: Magnetic resonance neurography (MRN) and myography (MRM) are emerging imaging methods for detecting diseases of the peripheral nerve system (PNS). Most patients with PNS diseases also undergo needle electromyography (EMG). This study examined whether EMG led to lesions that were detectable using MRN/MRM and whether these lesions could impair image interpretation. METHODS: Ten patients who underwent clinically indicated EMG were recruited. MRN/MRM was performed before and 2-6 h after EMG, and if achievable, 2-3 days later. T2 signal intensity (SI) of the tibialis anterior muscle (TA) was quantified, and sizes and SI of the new lesions were measured. Visual rating was performed independently by three neuroradiologists. RESULTS: T2 lesions at the site of needle insertion, defined as focal edema, were detectable in 9/10 patients. The mean edema size was 31.72 mm2 (SD = 14.42 mm2 ) at the first follow-up. Susceptibility-weighted imaging lesions, defined as (micro) hematomas were detected in 5/10 patients (mean size, 23.85 mm2 [SD = 12.59 mm2 ]). General muscle SI of the TA did not differ between pre- and post-EMG examinations. Lesions size was relatively small, and the readers described image interpretation as not impaired by these lesions. DISCUSSION: This study showed that focal edema and hematomas frequently occurred after needle EMG and could be observed using MRN/MRM. As general muscle SI was not affected and image interpretation was not impaired, we concluded that needle EMG did not interfere with MRN/MRM.
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Doenças do Sistema Nervoso Periférico , Humanos , Eletromiografia , Doenças do Sistema Nervoso Periférico/patologia , Imageamento por Ressonância Magnética/métodos , Miografia , Edema , HematomaRESUMO
PURPOSE: As measures of association between an adverse drug reaction (ADR) and exposure to a drug the reporting odds ratio (ROR) and the information component (IC) can be used. We sought to test the reliability of signal detection with these. METHODS: We simulated ADR counts as binomially distributed random numbers for different expected ADR frequencies and theoretical reporting odds ratios (RORs). We then calculated the empirical IC and the empirical ROR and their confidence intervals. The rate of signals that was detected despite a theoretical ROR of 1 represented the false positive rate, and represented the sensitivity if the ROR was >1. RESULTS: For expected case counts below 1 the false positive rate oscillates from 0.01 to 0.1 even though 0.025 were intended. Even beyond expected case counts of 5 oscillations can cover a range of 0.018 to 0.035. The first n oscillations with the largest amplitude are eliminated if a minimum case count of n is required. To detect an ROR of 2 with a sensitivity of 0.8, a minimum of 12 expected ADRs are required. In contrast, 2 expected ADRs suffice to detect an ROR of 4. CONCLUSION: Summaries of measures for disproportionality should include the expected number of cases in the group of interest if a signal was detected. If no signal was detected the sensitivity for the detection of a representative ROR or the minimum ROR that could be detected with probability 0.8 should be reported.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Razão de Chances , Reprodutibilidade dos Testes , Bases de Dados Factuais , FarmacovigilânciaRESUMO
BACKGROUND: Gliomas are often associated with symptoms including seizures. Most patients with high-grade gliomas are treated with radiotherapy or radio-chemotherapy. Since irradiation causes inflammation, it may initially aggravate symptoms. Studies focusing on seizure activity during radiotherapy for gliomas are not available. Such knowledge may improve patient monitoring and anti-epileptic treatment. This study evaluates seizure activity during radiotherapy for high-grade gliomas. METHODS: The primary objective this prospective interventional study is the evaluation of seizure activity during a course of radiotherapy for high-grade gliomas. Progression of seizure activity is defined as increased frequency of seizures by > 50%, increased severity of seizures, or initiation/increase by ≥25% of anti-epileptic medication. Seizure frequency up to 6 weeks following radiotherapy and electroencephalography activity typical for epilepsy will also be evaluated. Patients keep a seizure diary during and up to 6 weeks following radiotherapy. Every day, they will document number (and type) of seizures and anti-epileptic medication. Once a week, the findings of the diary are checked and discussed with a neurologist to initiate or adjust anti-epileptic medication, if necessary. Patients complete a questionnaire regarding their satisfaction with the seizure diary. If the dissatisfaction rate is > 40%, the seizure diary will be considered not suitable for the investigated indication. Thirty-five patients (32 patients plus drop-outs) should be enrolled. With this sample size, a one-sample binomial test with a one-sided significance level of 2.5% has a power of 80% to yield statistical significance, if the rate of patients with progression of seizure activity is 30% (rate under the alternative hypothesis), assuming a 'natural' background progression-rate of 10% without radiotherapy (null hypothesis). DISCUSSION: If an increase in seizure activity during a course of radiotherapy for high-grade glioma occurs, the findings of this study may pave the way for a larger prospective trial and will likely lead to closer patient monitoring and better anti-epileptic treatment. TRIAL REGISTRATION: clinicaltrials.gov ( NCT04552756 ); registered on 16th of September, 2020.
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Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Irradiação Craniana/efeitos adversos , Glioma/complicações , Glioma/patologia , Convulsões/diagnóstico , Convulsões/etiologia , Anticonvulsivantes/uso terapêutico , Neoplasias Encefálicas/radioterapia , Quimiorradioterapia , Irradiação Craniana/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Eletroencefalografia , Feminino , Glioma/radioterapia , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Convulsões/terapia , Avaliação de Sintomas , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Some groups of cardiovascular drugs (beta-blocking drugs, Ca antagonists, antiarrhythmics) are listed as potentially worsening myasthenia. An empirical basis for alternative recommendations for antihypertensive and antiarrhythmic therapy in myasthenia patients has not yet been provided. METHODS: From the World Health Organization pharmacovigilance database, we retrieved total and myasthenia-related counts of adverse drug reactions for various groups of drugs used in cardiovascular disease and drugs with related mechanism of action used in other indications. We calculated the reporting odds ratio as a measure of a disproportional fraction of myasthenia-related events among all events. A 95% confidence interval of reporting odds ratio (ROR) >1 was taken as an indication for a higher risk. Because our approach involves a considerable number of tests, this situation is referred to as a signal that requires additional confirmation. RESULTS: A signal for an increased risk was noted for tizanidine, for alpha-blocking drugs, for beta-blocking drugs, and for Ca antagonists. ROR indicated a lower-than-average risk for salbutamol, angiotensin receptor antagonists, oral anticoagulants, thrombocytic function inhibitors, and heparins. CONCLUSIONS: Angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, and diuretics seem to be safe in antihypertensive therapy. Surprisingly, and yet requiring confirmation by case reports, alpha receptor-blocking drugs seem to carry a risk of myasthenia worsening. Amiodarone seems to be a safe alternative in antiarrhythmic therapy in patients with myasthenia.
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Antagonistas de Receptores de Angiotensina , Hipertensão , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos/efeitos adversos , Diuréticos , Humanos , FarmacovigilânciaRESUMO
BACKGROUND AND PURPOSE: Many drugs can worsen myasthenia symptoms. The clinician usually relies on cautionary lists compiled according to case reports. We intended to provide a quantitative basis for a risk comparison within the groups of antiepileptic, antidepressant, neuroleptic, and sedative drugs. METHODS: We extracted adverse drug reaction (ADR) counts (total and myasthenia related) for drugs from these groups and calculated the reporting odds ratio (ROR) within the drug groups from the World Health Organization pharmacovigilance database. For a given drug, the ROR was increased above 1 if the proportion of myasthenia-related ADRs for this drug was larger than the same proportion for the rest of drugs in that same group. If the 95% confidence interval of ROR was >1, this was taken as a signal for a higher risk of the given drug as compared to the average of the respective group. RESULTS: Gabapentin, sertraline, citalopram, lithium, and amisulpride had a signal for the ROR to be increased above 1 within their respective groups. Bupropion, desvenlafaxine, duloxetine, escitalopram, and paroxetine had ROR values <1. For all other drugs, 1 was within the ROR confidence interval. CONCLUSIONS: For gabapentin and lithium, the analysis of RORs confirmed case reports and cautionary lists. For a number of antidepressant drugs associated with a higher-than-average risk, no case reports exist substantiating our results. For these drugs, special attention should be paid to this risk. The remarkable difference between citalopram and escitalopram could prompt experimental work to confirm differential influence of the two preparations on neuromuscular transmission.
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Antipsicóticos , Anticonvulsivantes , Antidepressivos/efeitos adversos , Bases de Dados Factuais , Humanos , Hipnóticos e Sedativos , FarmacovigilânciaRESUMO
BACKGROUND AND PURPOSE: The bedside head impulse test (bHIT) is used to differentiate vestibular neuritis (VN) from posterior circulation stroke (PCS) in patients presenting with acute vestibular syndrome (AVS). If assessed by neuro-otological experts, diagnostic accuracy is high. We report on its diagnostic accuracy when applied by nonexperts during routine clinical practice in the emergency department (ED), its impact on patient management, and the potential diagnostic yield of the video-oculography-supported head impulse test (vHIT). METHODS: Medical chart review of 38 AVS patients presenting to our university medical center's ED, assessed by neurology residents. We collected bHIT results (abnormal/peripheral or normal/central) and whether patients were admitted to the stroke unit or general neurological ward. Final diagnosis (VN, n = 24; PCS, n = 14) was determined by clinical course, magnetic resonance imaging, and vHIT. RESULTS: The bHIT's accuracy was only 58%. Its sensitivity for VN was high (88%), but due to many false-abnormal bHITs in PCS (36%), the specificity was low (64%). The vHIT yielded excellent specificity (100%) and moderate sensitivity (67%). The decision on the patient's further care was almost arbitrary and independent from the bHIT: 58% of VN and 57% of PCS patients were admitted to the stroke unit. CONCLUSIONS: The bHIT, applied by nonexperts during routine practice in the ED, has low accuracy, is too often mistaken as abnormal/peripheral, and is not consistently used for patients' in-hospital triage. As false-abnormal bHITs can lead to misdiagnosis/mistreatment of stroke patients, we recommend that bHIT applied by nonexperts should be reassessed by a neuro-otological expert or preferably quantitative vHIT in the ED.
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Acidente Vascular Cerebral , Neuronite Vestibular , Serviço Hospitalar de Emergência , Teste do Impulso da Cabeça , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Vertigem/diagnóstico , Vertigem/etiologia , Neuronite Vestibular/diagnósticoRESUMO
Despite many reports on visual processing deficits in psychotic disorders, studies are needed on the integration of visual and non-visual components of eye movement control to improve the understanding of sensorimotor information processing in these disorders. Non-visual inputs to eye movement control include prediction of future target velocity from extrapolation of past visual target movement and anticipation of future target movements. It is unclear whether non-visual input is impaired in patients with schizophrenia. We recorded smooth pursuit eye movements in 21 patients with schizophrenia spectrum disorder, 22 patients with bipolar disorder, and 24 controls. In a foveo-fugal ramp task, the target was either continuously visible or was blanked during movement. We determined peak gain (measuring overall performance), initial eye acceleration (measuring visually driven pursuit), deceleration after target extinction (measuring prediction), eye velocity drifts before onset of target visibility (measuring anticipation), and residual gain during blanking intervals (measuring anticipation and prediction). In both patient groups, initial eye acceleration was decreased and the ability to adjust eye acceleration to increasing target acceleration was impaired. In contrast, neither deceleration nor eye drift velocity was reduced in patients, implying unimpaired non-visual contributions to pursuit drive. Disturbances of eye movement control in psychotic disorders appear to be a consequence of deficits in sensorimotor transformation rather than a pure failure in adding cognitive contributions to pursuit drive in higher-order cortical circuits. More generally, this deficit might reflect a fundamental imbalance between processing external input and acting according to internal preferences.
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Transtorno Bipolar/fisiopatologia , Percepção de Movimento/fisiologia , Acompanhamento Ocular Uniforme/fisiologia , Esquizofrenia/fisiopatologia , Adolescente , Adulto , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Escalas de Graduação Psiquiátrica , Tempo de Reação/fisiologia , Adulto JovemRESUMO
OBJECTIVE: Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). METHODS: Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). RESULTS: Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. CONCLUSIONS: The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology.
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Aquaporina 4/sangue , Autoanticorpos/sangue , Neuromielite Óptica/sangue , Aquaporina 4/imunologia , Autoanticorpos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imuno-Histoquímica/métodos , Neuromielite Óptica/imunologia , Sensibilidade e EspecificidadeRESUMO
Alterations in sensorimotor processing and predictive mechanisms have both been proposed as the primary cause of eye tracking deficits in schizophrenia. 20 schizophrenia patients and 20 healthy controls were assessed on blocks of predictably moving visual targets at constant speeds of 10, 15 or 30°/s. To assess internal drive to the eye movement system based on predictions about the ongoing target movement, targets were blanked off for either 666 or 1,000 ms during the ongoing pursuit movement in additional conditions. Main parameters of interest were eye deceleration after extinction of the visual target and residual eye velocity during blanking intervals. Eye deceleration after target extinction, reflecting persistence of predictive signals, was slower in patients than in controls, implying greater rather than diminished utilization of predictive mechanisms for pursuit in schizophrenia. Further, residual gain was not impaired in patients indicating a basic integrity of internal predictive models. Pursuit velocity gain in patients was reduced in all conditions with visible targets replicating previous findings about a sensorimotor transformation deficit in schizophrenia. A pattern of slower eye deceleration and unimpaired residual gain during blanking intervals implies greater adherence to top-down predictive models for pursuit tracking in schizophrenia. This suggests that predictive modeling is relatively intact in schizophrenia and that the primary cause of abnormal visual pursuit is impaired sensorimotor transformation of the retinal error signal needed for the maintenance of accurate visually driven pursuit. This implies that disruption in extrastriate and sensorimotor systems rather than frontostriatal predictive mechanisms may underlie this widely reported endophenotypes for schizophrenia.
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Transtornos da Motilidade Ocular/etiologia , Acompanhamento Ocular Uniforme/fisiologia , Esquizofrenia/complicações , Adolescente , Adulto , Análise de Variância , Piscadela/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento/fisiologia , Desempenho Psicomotor , Tempo de Reação , Adulto JovemRESUMO
PURPOSE: To prospectively assess the incidence of Dropped Head Syndrome (DHS) in childhood cancer survivors (CCS) and to develop and evaluate a diagnostic algorithm for DHS. METHODS: A systematic literature search for DHS in combination with neck radiotherapy (RT) exposure was performed. Analyses and a combination of the most common examination methods were integrated into a diagnostic algorithm. Almost all CCSs visiting the local late effects clinic between May 2020 and April 2022 were included in the study. CCS exposed to neck RT with doses ≥ 19 Gy received standardized clinical and neurological assessment and, in case of abnormal results, an MRI scan to confirm muscle atrophy. RESULTS: Two hundred and five CCS were included of whom 41 received RT to the neck with ≥ 19 Gy. In the entire cohort and in the subgroup receiving RT, 2.4% and 12% of CCS were affected by DHS, respectively. Results of clinical and neurological assessment correlated well with MRI results. Neck circumference and neck/thigh ratio were lower after neck RT. Over 50% of CCS experienced neck disability and pain. CONCLUSIONS: A relevant proportion of CCS exposed to neck RT is affected by DHS. High concordance of MRI results with the neurological examination supports the clinical value of the diagnostic algorithm. Measurement of neck circumference might be an easy tool for assessment of neck muscle atrophy in survivors at risk. IMPLICATIONS FOR CANCER SURVIVORS: Integration of a diagnostic algorithm for DHS in standard long-term follow-up care facilitates diagnosis as well as initiation of early treatment and obviates the need for invasive examinations.
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Sobreviventes de Câncer , Neoplasias , Criança , Humanos , Algoritmos , Síndrome da Cabeça Caída , Atrofia Muscular/diagnóstico por imagem , Atrofia Muscular/etiologia , Neoplasias/terapia , Estudos ProspectivosRESUMO
BACKGROUND/AIM: Standard radiotherapy (RT) for glioblastoma lasts 6 weeks. We aimed to identify patients who would benefit from a hypofractionated approach. PATIENTS AND METHODS: In 167 patients receiving standard fractionation, 10 factors were analyzed for local control (LC) and overall survival (OS). A survival score was developed and compared to a previous instrument. RESULTS: On multivariate analysis, better LC was significantly associated with the presence of only one lesion and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation. Better OS was associated with one lesion, better performance status, MGMT promoter methylation, and receipt of chemotherapy. Lesion diameter ≤40 mm and upfront resection were associated with improved OS on univariate analyses. Based on assigning scores to these six factors, three groups, with 32-35, 36-44 and 45-48 points, were designed with 12-month OS-rates of 0%, 56%, and 92%, respectively. Accuracy in predicting death within 12 months and survival ≥12 months was 100% and 92%, respectively, versus 67% and 83% with the previous scoring system. CONCLUSION: A new survival score with higher accuracy was developed for patients with glioblastoma. Our model can be utilized to individualize RT dose-fractionation recommendations for glioblastoma.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/radioterapia , Glioblastoma/tratamento farmacológico , Temozolomida/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Dacarbazina/uso terapêutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Metilação de DNA , PrognósticoRESUMO
BACKGROUND/AIM: A recommendation of radiotherapy for patients with malignant gliomas may trigger emotional distress. Frequency and risk factors of this complication were investigated. PATIENTS AND METHODS: Prevalence of six emotional problems and 11 potential risk factors were evaluated in 103 patients irradiated for grade II-IV gliomas. p-Values <0.0045 were considered significant. RESULTS: Seventy-six patients (74%) had ≥1 emotional problem. Prevalence of specific emotional problems ranged between 23% and 63%. Associations were found between ≥5 physical problems and worry (p=0.0010), fear (p=0.0001), sadness (p=0.0023), depression (p=0.0006), and loss of interest (p=0.0006), and Karnofsky performance score ≤80 and depression (p=0.0002). Trends were found for physical problems and nervousness (p=0.040), age ≥60 years and depression (p=0.043) or loss of interest (p=0.045), grade IV glioma and sadness (p=0.042), and ≥2 involved sites and loss of interest (p=0.022). CONCLUSION: Three-fourths of glioma patients had pre-radiotherapy emotional distress. Psychological support should be offered very soon, particularly for high-risk patients.
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Neoplasias Encefálicas , Glioma , Angústia Psicológica , Humanos , Pessoa de Meia-Idade , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/patologia , Glioma/radioterapia , Glioma/patologia , Dosagem Radioterapêutica , Fatores de RiscoRESUMO
Patients with Parkinson's disease (PD) have difficulties in the control of self-guided (i.e., internally driven) movements. The basal ganglia provide a nonspecific internal cue for the development of a preparatory activity for a given movement in the sequence of repetitive movements. Controversy surrounds the question of whether PD patients are capable of (1) anticipating (before an external trigger appears; i.e., anticipation) and (2) predicting movement velocity once a moving target shortly disappears from the visual scene (i.e., prediction). To dissociate between these two components, we examined internally driven (extraretinal generated) smooth pursuit eye movements in PD patients and age-matched healthy controls by systematically varying target blanking periods of a trapezoidally moving target in four paradigms (initial blanking, midramp blanking, blanking after a short ramp, and no blanking). Compared to controls, PD patients showed (1) decreased smooth pursuit gain (without blanking), (2) deficient anticipatory pursuit (prolonged pursuit initiation latency; reduced eye velocity before target onset in the early onset blanking paradigm), and (3) preserved extraretinal predictive pursuit velocity (midramp target blanking). Deficient anticipation of future target motion was not related to either disease duration or the general motor impairment (UPDRS). We conclude that PD patients have difficulties in anticipating future target motion, which may play a role for the mechanisms involved in deficient gait initiation and termination of PD. In contrast, they remain unimpaired in their capacity of building up an internal representation of continuous target motion. This may explain the clinical advantage of medical devices that use visual motion to improve gait initiation (e.g., "PD glasses").
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Antecipação Psicológica , Transtornos da Motilidade Ocular/fisiopatologia , Doença de Parkinson/fisiopatologia , Acompanhamento Ocular Uniforme , Movimentos Sacádicos , Idoso , Análise de Variância , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Percepção de Movimento , Transtornos da Motilidade Ocular/etiologia , Transtornos da Motilidade Ocular/psicologia , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Desempenho PsicomotorRESUMO
BACKGROUND/AIM: Little is known regarding seizures during radiotherapy for brain tumors. This prospective study investigated seizure activity in patients irradiated for high-grade gliomas. PATIENTS AND METHODS: Using a seizure diary, progression of seizure activity was evaluated in 22 patients receiving chemoradiation for grade III (n=1) or IV (n=21) gliomas. Progression was defined as increased frequency of any and/or generalized seizures (>50%) or increased anti-epileptic medication (≥25%). Patients' satisfaction with the diary was assessed using a questionnaire (six scales of 1-7 points). Uni- and multivariable analyses were performed including baseline seizure activity, age, sex, resection, tumor site, performance score, and history of epilepsy/seizures. RESULTS: Ten patients (45%) experienced progression of seizure activity during their radiotherapy course, mainly due to increased seizure frequency (nine patients=41%). Mean values of patients' satisfaction scores ranged between 3.92 and 4.92 points. CONCLUSION: Radiotherapy of high-grade gliomas can increase seizure activity. Patients require close monitoring to initiate or adjust anti-epileptic medication.
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Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/patologia , Glioma/patologia , Glioma/radioterapia , Humanos , Estudos Prospectivos , Pesquisa , Convulsões/etiologiaRESUMO
BACKGROUND: Thrombolysis is a dynamic and time-dependent process influenced by the haemodynamic conditions. Currently there is no model that allows for time-continuous, non-contact measurements under physiological flow conditions. The aim of this work was to introduce such a model. METHODS: The model is based on a computer-controlled pump providing variable constant or pulsatile flows in a tube system filled with blood substitute. Clots can be fixed in a custom-built clot carrier within the tube system. The pressure decline at the clot carrier is measured as a novel way to measure lysis of the clot. With different experiments the hydrodynamic properties and reliability of the model were analyzed. Finally, the lysis rate of clots generated from human platelet rich plasma (PRP) was measured during a one hour combined application of diagnostic ultrasound (2 MHz, 0.179 W/cm2) and a thrombolytic agent (rt-PA) as it is commonly used for clinical sonothrombolysis treatments. RESULTS: All hydrodynamic parameters can be adjusted and measured with high accuracy. First experiments with sonothrombolysis demonstrated the feasibility of the model despite low lysis rates. CONCLUSIONS: The model allows to adjust accurately all hydrodynamic parameters affecting thrombolysis under physiological flow conditions and for non-contact, time-continuous measurements. Low lysis rates of first sonothrombolysis experiments are primarily attributable to the high stability of the used PRP-clots.
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Simulação por Computador , Modelos Biológicos , Trombose , Velocidade do Fluxo Sanguíneo , Humanos , Hidrodinâmica , Técnicas In Vitro , Reprodutibilidade dos Testes , Trombose/patologia , Trombose/fisiopatologia , Fatores de TempoRESUMO
Intravenous thrombolysis (IVT) is rarely performed in dizzy patients with acute vestibular syndrome (AVS) or acute imbalance (AIS) even if posterior circulation stroke (PCS) is suspected. Decision-making may be affected by uncertainties in discriminating central from peripheral vestibulopathy or concerns of IVT-related harm, particularly intracerebral hemorrhage (ICH), but related studies are missing. Using an in-house register of dizzy patients coming to the emergency room, we identified 29 AVS/AIS patients who presented within 4.5 h after onset, revealed clinical signs indicative of PCS (central oculomotor signs, mild focal abnormalities), and had non-contrast computed tomography (NCCT). Patients treated with IVT (n = 15) were compared to NoIVT patients (n = 14) with regard to clinical and imaging (including perfusion computed tomography, CTP) parameters, occurrence of ICH and short-term clinical outcome (NIHSS improvement; ability to walk independently). IVT and NoIVT patients did not differ in baseline characteristics, central oculomotor signs, or clinical outcome. IVT patients more often exhibited disabling vestibular symptoms (severe dizziness/vertigo, inability to stand unsupported) and focal abnormalities than NoIVT patients. There was no ICH in either group. CTP was performed in 0% of NoIVT versus 80% of IVT patients, seven of twelve revealing posterior circulation hypoperfusion. Comparison of initial hypoperfusion (CTP) and final stroke (NCCT) revealed IVT-related benefit (smaller lesion) in three of seven IVT patients. In AVS/AIS patients with suspected PCS, disabling vestibular symptoms, focal neurological deficits, and hypoperfusion on CTP seem to direct decision-making pro IVT. In our small cohort, there were no significant IVT-related clinical benefits, no IVT-related ICHs, and salvage of brain tissue in some patients.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica , Resultado do Tratamento , Vertigem/tratamento farmacológico , Vertigem/etiologiaRESUMO
Objective: The head impulse test (HIT) assesses the vestibulo-ocular reflex (VOR) and is used to differentiate vestibular neuritis (abnormal VOR) from stroke (normal VOR) in patients presenting with an acute vestibular syndrome (AVS). The video-oculography-based HIT (vHIT) quantifies VOR function and provides information imperceptible for the clinician during clinical bedside HIT. However, the vHIT-like an electrocardiogram-requires experienced interpretation, which is especially difficult in the emergency setting. This calls for a simple, reliable and rater-independent way of analysis. Methods: We retrospectively collected 171 vHITs performed in patients presenting with AVS to our emergency department. Three neuro-otological experts comprehensively assessed the vHITs including interpretability (artifacts), VOR gain (eye/head velocity ratio), velocity profile (abrupt decline) and corrective saccades (overt/covert). Their consensus rating (abnormal/peripheral vs. normal/central) was compared to a simple algorithm that automatically classified the vHITs based on a single VOR gain cutoff (0.7). Results: Inter-rater agreement between experts was high (Fleiss' kappa = 0.74). Five (2.9 %) vHITs were "uninterpretable" according to experts' consensus, 80 (46.8 %) were rated "normal" and 86 (50.3 %) "abnormal". The algorithm had substantial agreement with the experts' consensus (Cohen's kappa = 0.75). Importantly, it correctly classified all of the normal/central vHITs denoted by the experts (100% specificity) and at the same time it had sufficient sensitivity (75.6%) in detecting abnormal/peripheral vHITs. Conclusion: A simple, automated, gain-based evaluation of the vHIT reliably detects normal/central VOR and may be a feasible and effective tool to screen AVS patients for potentially underlying stroke in the emergency setting.
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BACKGROUND/AIM: In a previous study investigating radiotherapy for newly diagnosed glioblastoma multiforme (GBM), significant or almost significant associations with survival were found for performance status, upfront resection, O6-methylguanine-DNA methyl-transferase (MGMT) promoter methylation and unifocal GBM. This study aimed to create a survival score based on these factors. PATIENTS AND METHODS: Most of the 81 patients included received resection of GBM followed by radiochemotherapy (59.4 Gy/33 or 60 Gy/30 fractions). The previously identified predictors of survival were re-evaluated. Factors significantly associated with survival were used for the score. RESULTS: All factors were significantly associated with survival. For each factor, 0 points (less favorable survival) or 1 point (more favorable survival) were assigned and added for each patient. Three groups were designed, 0-1 (n=10), 2 (n=21) and 3-4 points (n=50); 12-month survival rates were 0%, 38% and 78% (p<0.001). CONCLUSION: A new survival score was created for patients requiring radiotherapy for GBM that can improve treatment personalization.