Rey-Osterrieth complex figure test: Comparison of traditional and qualitative scoring systems after unilateral temporal lobectomy.

OBJECTIVE: We compared the performance on the Rey-Osterrieth Complex Figure Test (ROCF) of patients that had undergone unilateral anterior temporal lobectomy under both Taylor's and Loring's scoring systems to identify the sensitivity and specificity of each item for differentiating visuospatial memory deficits. METHOD: We administered the ROCF to evaluate the visual memory of 37 left anterior temporal lobectomy (LATL) and 38 right anterior temporal lobectomy (RATL) patients with unilateral temporal lobe epilepsy who had undergone a standard unilateral anterior temporal lobectomy between 1996 and 2010. Fisher's exact and Qui-Quadrado tests were used to analyze the relationships between the qualitative variables. The Mann-Whitney U test was used to compare the quantitative variables from the right and left sides. RESULTS: RATL patients performed worse than LATL patients based on the total score for delayed recall (DR) (p = 0.012). The scoring system's showed a specificity of 97.2% & 78.9% and sensitivity of 10.5% & 62.2% on DR, for the Taylor and Loring systems respectively. Our detailed analysis of certain items showed that some differed between the groups in terms of the presence/absence, correct reproduction, and errors of those items. Loring' errors I, IV, and X on DR and errors IV and X on immediate recall were more frequent in the RATL group. CONCLUSIONS: The use of these two scoring systems combined may help maximize sensitivity and specificity with clinical populations. Further, our analyses showed that items could be clustered better and different weights could be given to them to maximize sensitivity and specificity.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology.

Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology / Canabinoides em Neurologia - Artigo de posicionamento dos Departamentos Científicos da Academia Brasileira de Neurologia

ABSTRACT Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

RESUMO Os canabinoides compreendem os endocanabinoides, fitocanabinoides e os canabinoides sintéticos e desempenham ações no sistema nervoso central e periférico. Uma quantidade enorme de publicações tem sido lançada nos últimos anos, embora a cannabis seja conhecida por milênios. Os Departamentos Científicos da Academia Brasileira de Neurologia descreveram as evidências do uso médico em suas áreas. A literatura está em constantes mudanças e possíveis novas evidências podem surgir nos próximos dias ou meses. A prescrição dessas substâncias deve ser discutida com os pacientes e suas famílias, com conhecimento sobre eventos adversos e sua eficácia.

Nonverbal fluency assessed by the five-point test in epilepsy patients with unilateral mesial temporal sclerosis-a Brazilian study.

OBJECTIVE: To investigate the performance of epilepsy patients diagnosed with unilateral mesial temporal sclerosis (MTS) on a nonverbal fluency measure using the five-point test (FPT). Our secondary aim was to investigate any differences in FPT and verbal fluency test (VFT) scores between left and right MTS. We hypothesized that scores on the FPT, commonly utilized in the assessment of individuals with presumed frontal lobe damage, would be lower in patients with temporal lobe dysfunction. METHOD: One hundred eighty patients diagnosed with temporal lobe epilepsy (TLE) and 150 healthy controls (HCs) were included in this retrospective study. We analyzed correlations between scores obtained from FPT and phonemic and semantic VFT, and scores according to the lateralization of epileptogenic focus in the TLE group. RESULTS: Overall, the TLE patients had lower performance than the HCs on the FPT, but no differences were observed on perseverance rates (p = 0.992). Statistically significant difference was found in both sections of the VFT in association with the lateralization of the epileptogenic zone (p < 0.001). As for the FPT, differences did not reach statistical significance (p = 0.0857). CONCLUSIONS: Our results support the hypothesis of involvement of the temporal areas on tasks such as the FPT, despite the lack of a lateralizing effect. Our findings also contribute to better understanding of the role of the FPT in assessment of executive function in patients with unilateral MTS, and provide further psychometric data on a native Brazilian population.

CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment.

Phenytoin (PHT) is an antiepileptic drug widely used in the treatment of focal epilepsy and status epilepticus, and effective in controlling focal seizures with and without tonic-clonic generalization and status epilepticus. The metabolization of PHT is carried out by two oxidative cytochrome P450 enzymes CYP2C9 and CYP2C19; 90% of this metabolization is done by CYP2C9 and the remaining 10% by CYP2C19. Genetic polymorphism of CYP2C9 may reduce the metabolism of PHT by 25-50% in patients with variants *2 and *3 compared to those with wild-type variant *1. The frequency distribution of CYP2C9 polymorphism alleles in patients with epilepsy around the world ranges from 4.5 to 13.6%, being less frequent in African-Americans and Asians. PHT has a narrow therapeutic range and a nonlinear pharmacokinetic profile; hence, its poor metabolization has significant clinical implications as it causes more frequent and more serious adverse effects requiring discontinuation of treatment, even if it had been effective. There is evidence that polymorphisms of CYP2C9 and the use of PHT are associated with an increase in the frequency of some side effects, such as cerebellar atrophy, gingival hypertrophy or acute cutaneous reactions. The presence of HLA-B*15:02 and CYP2C9 *2 or *3 in the same patient increases the risk of Stevens-Johnson syndrome and toxic epidermal necrolysis; hence, PHT should not be prescribed in these patients. In patients with CYP2C9 *1/*2 or *1/*3 alleles (intermediate metabolizers), the usual PHT maintenance dose (5-10 mg/kg/day) must be reduced by 25%, and in those with CYP2C9 *2/*2, *2/*3 or *3/*3 alleles (poor metabolizers), the dose must be reduced by 50%. It is controversial whether CYP2C9 genotyping should be done before starting PHT treatment. In this paper, we aim to review the influence of CYP2C9 polymorphism on the metabolization of PHT and the clinical implications of poor metabolization in the treatment of epilepsies.

Refractory epilepsy in children with brain tumors. The urgency of neurosurgery.

In order to verify indications for surgery, 27 patients with refractory epileptic seizures and brain tumor, aged up to 19 years at the time of surgery, were studied between 1996 and 2013 and followed up for at least one year. The mean interval between the onset of seizures and the diagnosis of the tumor was 3.6 years, and from diagnosis to the surgery, 18 months. The location of the tumor was in the temporal lobe in 16, with ganglioglioma and dysembryoplastic neuroepithelial tumors being the most frequent. Among the patients, 92.5% and 90.4% were seizure-free in the first and fifth year after surgery, respectively. Twelve of 16 children were successful in becoming drug-free, with complete withdrawal by 3.2 years. Surgery proved to be potentially curative and safe in these cases, suggesting that the tumor diagnosis and surgery cannot be postponed.

Neuromodulation in refractory epilepsy: Brazilian specialists consensus.

Epilepsy is a potentially devastating brain disorder characterized by a predisposition to spontaneous epileptic seizures. In patients with medically refractory epilepsy, new non-pharmacological therapeutic approaches may be considered. In this scenario, palliative surgery such as vagus nerve stimulation (VNS) or deep brain stimulation (DBS) may be indicated in a subset of patients. In this paper we make recommendations for the use of VNS and DBS in patients in Brazil with refractory epilepsy.

Neuromodulation in refractory epilepsy: Brazilian specialists consensus / Neuromodulação em epilepsia refratária: consenso dos especialistas brasileiros

ABSTRACT Epilepsy is a potentially devastating brain disorder characterized by a predisposition to spontaneous epileptic seizures. In patients with medically refractory epilepsy, new non-pharmacological therapeutic approaches may be considered. In this scenario, palliative surgery such as vagus nerve stimulation (VNS) or deep brain stimulation (DBS) may be indicated in a subset of patients. In this paper we make recommendations for the use of VNS and DBS in patients in Brazil with refractory epilepsy.

RESUMO Epilepsia é uma doença cerebral potencialmente devastadora caracterizada por predisposição em gerar crises epilépticas espontâneas. Em pacientes com epilepsia refratária novas abordagens terapêuticas, não farmacológicas, podem ser consideradas. Neste cenário, cirurgias paliativas, como a estimulação do nervo vago (VNS) ou estimulação cerebral profunda (DBS) podem ser indicadas em um subgrupo de pacientes. Neste trabalho sugerimos recomendações sobre as indicações de uso do VNS e do DBS em pacientes com epilepsia refratária no Brasil.

Refractory epilepsy in children with brain tumors. The urgency of neurosurgery / Epilepsia refratária em crianças com tumores cerebrais. A urgência de neurocirurgia

ABSTRACT In order to verify indications for surgery, 27 patients with refractory epileptic seizures and brain tumor, aged up to 19 years at the time of surgery, were studied between 1996 and 2013 and followed up for at least one year. The mean interval between the onset of seizures and the diagnosis of the tumor was 3.6 years, and from diagnosis to the surgery, 18 months. The location of the tumor was in the temporal lobe in 16, with ganglioglioma and dysembryoplastic neuroepithelial tumors being the most frequent. Among the patients, 92.5% and 90.4% were seizure-free in the first and fifth year after surgery, respectively. Twelve of 16 children were successful in becoming drug-free, with complete withdrawal by 3.2 years. Surgery proved to be potentially curative and safe in these cases, suggesting that the tumor diagnosis and surgery cannot be postponed.

RESUMO A fim de verificar os aspectos da indicação cirúrgica, vinte e sete pacientes com epilepsia refratária secundária a tumor cerebral, com idade de até 19 anos na cirurgia, operados entre 1996 e 2013 e seguidos por pelo menos um ano, foram estudados. O intervalo médio entre o início das crises e o diagnóstico do tumor foi de 3,6 anos, e deste para a cirurgia, 18 meses. A localização do tumor foi lobo temporal em 16, sendo ganglioglioma e DNET os tipos mais frequentes. Entre os pacientes, 92,5% e 90,4% estavam livres de crises no primeiro e no quinto ano após a cirurgia, respectivamente. Doze de 16 crianças obtiveram sucesso na retirada de drogas, com a média de tempo de 3,2 anos após o procedimento. A cirurgia provou ser potencialmente curativa e segura nestes casos, o que sugere que perante o diagnóstico de tumor esta não pode ser adiada.

Improving first responders' psychogenic nonepileptic seizures diagnosis accuracy: Development and validation of a 6-item bedside diagnostic tool.

OBJECTIVE: Epileptic seizures (ES) are often seen as a medical emergency, and their immediate and accurate recognition are pivotal in providing acute care. However, a number of clinical situations may mimic ES, potentially leading to misdiagnosis at the emergency room and to inappropriate prescription of antiepileptic drugs (AED) in the acute and chronic settings. Psychogenic nonepileptic seizures (PNES) play a major role in this scenario and often delay the correct diagnosis and increase treatment morbidity and cost. First responders often conduct the initial assessment of these patients, and their impression may be decisive in the prehospital approach to seizures. We sought to investigate and improve the accuracy of PNES diagnosis among professionals involved in the initial assistance to patients with seizures. METHODS: Fifty-three registered nurses, 34 emergency physicians, 33 senior year medical students, and 12 neurology residents took a short training program consisting of an initial video-based seizure assessment test (pretest), immediately followed by a 30-minute presentation of a 6-item bedside diagnostic tool and then a video-based reassessment (posttest). Baseline status and learning curves were determined. RESULTS: The distinct professional categories showed no significant differences in their ability to diagnose PNES on both pretests and posttests. All groups improved diagnostic skills after the instructional program. SIGNIFICANCE: The findings helped determine the best identifiable PNES clinical signs and to provide initial validation to a novel diagnostic instrument. In addition, our results showed that educational measures might help in the identification of PNES by first responders, which may decrease the treatment gap.

Looking for complexity in quantitative semiology of frontal and temporal lobe seizures using neuroethology and graph theory.

Epileptic syndromes and seizures are the expression of complex brain systems. Because no analysis of complexity has been applied to epileptic seizure semiology, our goal was to apply neuroethology and graph analysis to the study of the complexity of behavioral manifestations of epileptic seizures in human frontal lobe epilepsy (FLE) and temporal lobe epilepsy (TLE). We analyzed the video recordings of 120 seizures of 18 patients with FLE and 28 seizures of 28 patients with TLE. All patients were seizure-free >1 year after surgery (Engel Class I). All patients' behavioral sequences were analyzed by means of a glossary containing all behaviors and analyzed for neuroethology (Ethomatic software). The same series were used for graph analysis (CYTOSCAPE). Behaviors, displayed as nodes, were connected by edges to other nodes according to their temporal sequence of appearance. Using neuroethology analysis, we confirmed data in the literature such as in FLE: brief/frequent seizures, complex motor behaviors, head and eye version, unilateral/bilateral tonic posturing, speech arrest, vocalization, and rapid postictal recovery and in the case of TLE: presence of epigastric aura, lateralized dystonias, impairment of consciousness/speech during ictal and postictal periods, and development of secondary generalization. Using graph analysis metrics of FLE and TLE confirmed data from flowcharts. However, because of the algorithms we used, they highlighted more powerfully the connectivity and complex associations among behaviors in a quite selective manner, depending on the origin of the seizures. The algorithms we used are commonly employed to track brain connectivity from EEG and MRI sources, which makes our study very promising for future studies of complexity in this field.

Are children affected by epileptic neuropsychiatric comorbidities?

Childhood-onset epilepsy is associated with psychiatric and cognitive difficulties and with poor social outcomes in adulthood. Some antiepileptic drugs adversely affect behavior in susceptible children with easy-to-control or refractory epilepsies, contributing to a high risk of psychological and psychiatric disturbance. Studies had demonstrated that patients with benign rolandic epilepsy and absence epilepsy had more aggressive behavior, depression, and anxiety disorders than control children. Psychiatric comorbidities are strongly associated with a poor long-term health-related quality of life in childhood-onset epilepsy, which suggests that comprehensive epilepsy care must include screening and long-term treatment for these conditions, even if seizures remit.

Lamotrigine therapeutic drug monitoring in a tertiary epilepsy centre / Monitorização terapêutica da lamotrigina em um centro terciário de epilepsia

Objective: to review the experience with lamotrigine therapeutic drug monitoring in a tertiary epilepsy centre aiming to characterize the plasma concentrations profile. Methods: inclusion of adults and children to whom lamotrigine concentrations were requested from October 2008 to April 2010. A chromatographic method was validated to determine lamotrigine concentrations. Reference range adopted (plasma): 2.5-15.0 mg/L. Results: 115 patients were included (86 adults, 29 children). Mean±standard deviation lamotrigine dosages for adults and children were statistically different (5.1±2.0 versus 7.4±3.4 mg/kg/day respectively, p<0.0001), so as lamotrigine concentrations (5.13±4.0 versus 9.0±5.6 mg/L respectively, p=0.0006). Approximately 68% of all quantifications were within the reference range. From the 29 quantifications below 2.5 mg/L, 27 corresponded to lamotrigine+enzyme inducers therapies. There was no correlation between lamotrigine concentrations and dosages neither for pediatric nor for adult groups. Patients on monotherapy had lamotrigine concentrations significantly higher than those on lamotrigine+inducers therapies (p<0.001), and patients on lamotrigine+valproic acid therapy had lamotrigine concentrations higher than those on lamotrigine+inducers (p<0.001). There was no significant difference among mean dosages according to different comedications. Conclusion: our observations about the influence of polytherapies on lamotrigine pharmacokinetics confirm the relevance of quantifying this antiepileptic drug plasma concentrations in the process of treatment optimization...

Objetivo: revisar a experiência de um centro terciário de epilepsia com a monitorização terapêutica da lamotrigina objetivando caracterizar o perfil de concentrações plasmáticas encontradas. Métodos: inclusão de todos adultos e crianças para os quais solicitou-se quantificação plasmáticas de lamotrigina de Outubro/2008 a Abril/2010. Um método cromatográfico foi validado para determinar as concentrações de lamotrigina. Intervalo de referência adotado (plasma): 2.5-15.0 mg/L. Resultados: 115 pacientes foram incluídos (86 adultos, 29 crianças). Média±desvio-padrão das doses de lamotrigina para adultos e crianças foram significativamente diferentes (5.1±2.0 versus 7.4±3.4 mg/kg/dia respectivamente, p<0.0001), assim como as concentrações (5.13±4.0 versus 9.0±5.6 mg/L, p=0.0006). Aproximadamente 68% das quantificações estavam dentro do intervalo de referência. Das 29 quantificações abaixo de 2.5 mg/L, 27 correspondiam a associações lamotrigina+indutores enzimáticos. Não houve correlação entre concentrações e doses de lamotrigina. Pacientes em monoterapia tiveram concentrações de lamotrigina significativamente maiores do que pacientes utilizando lamotrigina+indutores enzimáticos (p<0.001); pacientes em uso de lamotrigina+ácido valproico apresentaram concentrações maiores comparativamente àqueles em uso de lamotrigina+indutores (p<0.001). Não houve diferença significativa entre doses médias de acordo com diferentes comedicações. Conclusão: a influência de politerapias sobre a farmacocinética da lamotrigina confirma a relevância dese quantificar as concentrações plasmáticas deste antiepilético no processo de otimização terapêutica...

Epilepsia / Epilepsy

Epilepsia constitui um grupo de sinais e sintomas que se podem manifestar de forma variada, tendo geralmente características estereotipadas em um mesmo paciente. O diagnóstico de epilepsia é essencialmente clínico, baseado na história do sintoma descrito pelo paciente e por pessoas que tenham presenciado as crises. A realização de exames de investigação tem como objetivo definir qual tipo de epilepsia determinado paciente apresenta e as suas causas. Os principais exames realizados na investigação são o eletroencefalograma de rotina e a ressonância magnética de encéfalo. Em alguns pacientes em que se faz necessária uma melhor caracterização das crises ou em que haja dúvida do diagnóstico ou tenham indicação para o tratamento cirúrgico da epilepsia a monitorização prolongada por videoeletroencefalograma é indicado. O tratamento medicamentoso deverá sempre ser instituído, para aqueles pacientes que não apresentaram controle satisfatório das crises o tratamento cirúrgico poderá ser indicado. O prognóstico em longo prazo é favorável, com controle total das crises em aproximadamente 60% dos casos, sendo que aproximadamente 20% podem beneficiar-se com o tratamento cirúrgico.

Effect of the classic ketogenic diet on the treatment of refractory epileptic seizures / Efeito da dieta cetogênica clássica no tratamento de crises epilépticas refratárias

OBJECTIVE:The ketogenic diet is used as a therapeutic alternative for the treatment of epilepsy in patients with refractory epilepsy. It simulates biochemical changes typical of fasting. The present study verified the nutritional impact of the ketogenic diet on children with refractory epilepsy. METHODS: Nutritional status data (dietary, biochemical and anthropometric measurements), seizure frequency, and adverse events were collected from the medical records and during outpatient clinic visits of children over a period of 36 months. RESULTS: Of the 29 children who initiated the ketogenic diet, 75.8% presented fewer seizures after one month of treatment. After six months, 48.3% of the patients had at least a 90.0% decrease in seizure frequency, and 50.0% of these patients presented total seizure remission. At 12 months, eight patients continued to show positive results, and seven of these children remained on the ketogenic diet for 24 months. There was an improvement of the nutritional status at 24 months, especially in terms of weight, which culminated with the recovery of proper weightforheight. There were no significant changes in biochemical indices (total cholesterol and components, triglycerides, albumin, total protein, creatinine, glycemia, serum aspartate transaminase and serum alanine transaminase). Serum cholesterol levels increased significantly in the first month, fell in the following six months, and remained within the normal limits thereafter. CONCLUSION: In conclusion, patients on the classic ketogenic diet for at least 24 months gained weight. Moreover, approximately one third of the patients achieved significant reduction in seizure frequency, and some patients achieved total remission.

OBJETIVO: A dieta cetogênica é empregada como uma terapia alternativa para o tratamento da epilepsia em pacientes com epilepsia refratária e simula as alterações bioquímicas de jejum. Neste trabalho, verificouse o impacto nutricional da dieta cetogênica em crianças com epilepsia refratária. MÉTODOS: Os dados sobre o estado nutricional (bioquímica, alimentar e medidas antropométricas), a frequência de crises e os eventos adversos de crianças acompanhadas durante 36 meses foram coletados de prontuários médicos e visitas ambulatoriais. RESULTADOS: Vinte e nove crianças iniciaram o tratamento; após um mês, 75,8% apresentaram redução das crises. Em seis meses, 48,3% dos pacientes tiveram pelo menos 90,0% de redução na frequência de crises, e, desses, 50,0% obtiveram o controle completo das crises. Aos doze meses, oito pacientes continuaram a apresentar Resultados positivos, e, desses, sete permaneceram em dieta cetogênica durante 24 meses. Observouse melhora do estado nutricional aos 24 meses de tratamento, especialmente em termos de peso, o que indica a recuperação da condição peso para altura. Não houve mudanças significativas nos índices bioquímicos analisados (colesterol total e de componentes, triglicerídeos, albumina, proteína total, creatinina, glicemia, transaminase glutâmico oxalacética sérica e transaminase glutâmico pirúvico sérica). Os níveis de colesterol aumentaram significativamente no primeiro mês, mas diminuíram nos seis meses seguintes e, posteriormente, se mantiveram dentro dos valores de referência. CONCLUSÃO: Os pacientes em uso da dieta cetogênica clássica por pelo menos 24 meses apresentaram melhora de peso e cerca de um terço dos pacientes conseguiu uma redução significativa da frequência de crises, com alguns pacientes completamente livres delas.

Validation of the Subjective Handicap of Epilepsy (SHE) in Brazilian patients with epilepsy.

The objectives of the study were to translate and adapt the Subjective Handicap of Epilepsy (SHE) instrument to Brazilian Portuguese and to determine its psychometric properties for the evaluation of quality of life in patients with epilepsy. A sample of 448 adult patients with epilepsy with different clinical profiles (investigation, preoperative period, postoperative period, and drug treatment follow-up) was evaluated with the SHE and the Epilepsy Surgery Inventory (ESI-55). Exploratory factorial analysis demonstrated that four factors explained 60.47% of the variance and were sensitive to discriminate the different clinical groups, with the preoperative group having the poorest quality of life. Internal consistency ranged from 0.92 to 0.96, and concurrent validity with the ESI-55 was moderate/strong (0.32-0.70). Test-retest reliability was confirmed, with an ICC value of 0.54 (2 days), 0.91 (7 days), and 0.97 (30 days). The SHE had satisfactory psychometric qualities for use in the Brazilian population, similar to those of the original version. The instrument seems to be more adequate in psychometric terms for the postoperative and drug treatment follow-up groups, and its use should be encouraged.

Addressing overtreatment in patients with refractory epilepsy at a tertiary referral centre in Brazil.

BACKGROUND: Patients with refractory epilepsy often have impaired quality of life (QOL) as a consequence of seizures and adverse effects of antiepileptic drugs. We assessed the impact of adverse effects on QOL and the utility of a structured instrument to help the physician manage adverse effects in patients with refractory epilepsy. METHODS: Clinical characteristics, drug treatment and adverse effects were evaluated in 102 patients with refractory epilepsy at a single tertiary referral centre. The Adverse Events Profile (AEP) and Quality of Life in Epilepsy-31 (QOLIE-31) questionnaires were completed at baseline and after six months. At baseline, patients with a high burden of adverse effects (AEP scores ≥45) were randomized to an intervention or control group. AEP scores in the intervention group were available to the physician as an instrument to help to reduce adverse effects. RESULTS: Ninety-five patients (93.1%) were on polytherapy. Sixty-six completed the questionnaires and, of these, 43 (65.1%) had a high AE burden and were randomized to the intervention and control group. QOLIE-31 scores were inversely correlated with AEP scores at both visits. Among randomized patients, AEP scores tended to decrease between the baseline and the final visit without significant differences between groups (intervention group: 54.1 ±â€Š6.1 vs 51.1 ±â€Š9.1; control group: 55.8 ±â€Š5.8 vs 50.5 ±â€Š12.2). QOLI-31 scores did not change substantially between visits (intervention group: 45.9 ±â€Š17.4 vs 48.4 ±â€Š14; control group: 47.5 ±â€Š15.7 vs 45.2 ±â€Š18.9). CONCLUSION: A significant proportion of patients had a high toxicity burden which had an impact on their QOL. Reduction of overtreatment is a difficult challenge which cannot be addressed solely by providing a structured assessment of adverse effects, but requires a more comprehensive approach aimed at optimizing the many components of the management strategy.