The Effects of Brain Tumours upon Medical Decision-Making Capacity.

PURPOSE OF REVIEW: Informed consent is the integral part of good medical practice in patients with brain tumours. Capacity to consent may be affected by the brain disorder or its treatment. We intend to draw upon the current neuro-oncology literature to discuss the influence intracranial tumours have upon patients' capacity to consent to treatment and research. RECENT FINDINGS: We performed a systematic review of studies of capacity to consent for treatment or research in patients with intracranial tumours. The search retrieved 1597 papers of which 8 were considered eligible for review. Although there are obvious inherent limitations to solely assessing cognition, most research consistently demonstrated increased risk of incapacity in brain tumour patients with cognitive impairment. Specific items in cognitive screening batteries, for example Semantic Verbal Fluency Test (SVFT), Hopkins Verbal Learning Test (HVLT-Recall), and Trail Making Test A/B (TMT), are simple, easily applied tests that may act as significant red flags to identify patients at increased risk of incapacity and who subsequently will require additional cognitive/psychiatric evaluation or more formal tests for capacity to consent for treatment or research.

Patients' and physicians' interpretation of chemotherapy-induced peripheral neurotoxicity.

To test if and how chemotherapy-induced peripheral neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. We performed a secondary analysis of the CI-PeriNomS study which included 281 patients with stable CIPN. We tested: (a) the association between patients' perception of activity limitation in performing eight common tasks and neurological impairment and (b) how the responses to questions related to these daily activities are interpreted by the treating oncologist. To achieve this, we compared patients' perception of their activity limitation with neurological assessment and the oncologists' blind interpretation. Distribution of the scores attributed by oncologists to each daily life maximum limitation ("impossible") generated three groups: Group 1 included limitations oncologists attributed mainly to motor impairment; Group 2 ones mainly attributed to sensory impairment and Group 3 ones with uncertain motor and sensory impairment. Only a subset of questions showed a significant trend between severity in subjective limitation, reported by patients, and neurological impairment. In Group 1, neurological examination confirmed motor impairment in only 51%-65% of patients; 76%-78% of them also had vibration perception impairment. In Group 2, sensory impairment ranged from 84% to 100%; some degree of motor impairment occurred in 43%-56% of them. In Group 3 strength reduction was observed in 49%-50% and sensory perception was altered in up to 82%. Interpretation provided by the panel of experienced oncologists was inconsistent with the neurological impairment. These observations highlight the need of a core set of outcome measures for future CIPN trials.

Correspondence between neurophysiological and clinical measurements of chemotherapy-induced peripheral neuropathy: secondary analysis of data from the CI-PeriNomS study.

Chemotherapy-induced peripheral neuropathy (CIPN) lacks standardized clinical measurement. The objective of the current secondary analysis was to examine data from the CIPN Outcomes Standardization (CI-PeriNomS) study for associations between clinical examinations and neurophysiological abnormalities. Logistic regression estimated the strength of associations of vibration, pin, and monofilament examinations with lower limb sensory and motor amplitudes. Examinations were classified as normal (0), moderately abnormal (1), or severely abnormal (2). Among 218 participants, those with class 1 upper extremity (UE) and classes 1 or 2 lower extremity (LE) monofilament abnormality were 2.79 (95% confidence interval [CI]: 1.28-6.07), 3.49 (95%CI: 1.61-7.55), and 4.42 (95%CI: 1.35-14.46) times more likely to have abnormal sural nerve amplitudes, respectively, compared to individuals with normal examinations. Likewise, those with class 2 UE and classes 1 or 2 LE vibration abnormality were 8.65 (95%CI: 1.81-41.42), 2.54 (95%CI: 1.19-5.41), and 7.47 (95%CI: 2.49-22.40) times more likely to have abnormal sural nerve amplitudes, respectively, compared to participants with normal examinations. Abnormalities in vibration and monofilament examinations are associated with abnormal sural nerve amplitudes and are useful in identifying CIPN.

Antiepileptic drugs for treating seizures in adults with brain tumours.

BACKGROUND: Seizures are a common symptom of brain tumours. The mainstay of treatment for seizures is medical therapy with antiepileptic drugs. OBJECTIVES: To evaluate the relative effectiveness and tolerability of antiepileptic drugs commonly used to treat seizures in adults with brain tumours. SEARCH STRATEGY: We searched CENTRAL (Issue 2 of 4, The Cochrane Library 2011), MEDLINE (1948 to May week 3, 2011) and EMBASE (1980 to 31 May 2011) databases. In addition, we handsearched articles published since 2000 in the following journals selected by the authors: Epilepsia; The Lancet Neurology and Neuro-Oncology. SELECTION CRITERIA: Controlled clinical trials with random allocation of the use of antiepileptic drugs to treat seizures in adults with brain tumours. DATA COLLECTION AND ANALYSIS: Both review authors screened the search results and reviewed the abstracts of potentially relevant articles before retrieving the full text of eligible articles. MAIN RESULTS: Only one trial met the inclusion criteria for this review which was a small, open-label, unblinded, randomised trial of the safety and feasibility of switching from phenytoin to levetiracetam monotherapy or continuing phenytoin for glioma-related seizure control following craniotomy (Lim 2009). Levetiracetam (a non enzyme-inducing antiepileptic drug) appears to have been at least as well tolerated and as effective as phenytoin (an enzyme-inducing antiepileptic drug) for the treatment of seizures in people with brain tumours. Eighty-seven per cent of participants treated with levetiracetam were free of seizures at six months compared with 75% of participants treated with phenytoin. There is one ongoing study of levetiracetam versus pregabalin for the treatment of seizures in adults undergoing chemotherapy, radiotherapy,or both for primary brain tumours. No data from this study were available at the time of preparing this review. AUTHORS' CONCLUSIONS: There is a lack of robust, randomised, controlled evidence to support the choice of antiepileptic drug for the treatment of seizures in adults with brain tumours. While some authors support the use of non enzyme-inducing antiepileptic drugs, reliable, comparative evidence to provide clinical justification for this is limited. There is a need for further large, randomised, controlled trials in this area.

Disease course of neurofibromatosis type 2: a 30-year follow-up study of 353 patients seen at a single institution.

BACKGROUND: Limited data exist on the disease course of neurofibromatosis type 2 (NF2) to guide clinical trial design. METHODS: A prospective database of patients meeting NF2 diagnostic criteria, reviewed between 1990 and 2020, was evaluated. Follow-up to first vestibular schwannoma (VS) intervention and death was assessed by univariate analysis and stratified by age at onset, era referred, and inheritance type. Interventions for NF2-related tumors were assessed. Cox regression was performed to determine the relationship between individual factors from time of diagnosis to NF2-related death. RESULTS: Three hundred and fifty-three patients were evaluated. During 4643.1 follow-up years from diagnosis to censoring, 60 patients (17.0%) died. The annual mean number of patients undergoing VS surgery or radiotherapy declined, from 4.66 and 1.65, respectively, per 100 NF2 patients in 1990-1999 to 2.11 and 1.01 in 2010-2020, as the number receiving bevacizumab increased (2.51 per 100 NF2 patients in 2010-2020). Five patients stopped bevacizumab to remove growing meningioma or spinal schwannoma. 153/353 (43.3%) had at least one neurosurgical intervention/radiation treatment within 5 years of diagnosis. Patients asymptomatic at diagnosis had longer time to intervention and better survival compared to those presenting with symptoms. Those symptomatically presenting <16 and >40 years had poorer overall survival than those presenting at 26-39 years (P = .03 and P = .02, respectively) but those presenting between 16 and 39 had shorter time to VS intervention. Individuals with de novo constitutional variants had worse survival than those with de novo mosaic or inherited disease (P = .004). CONCLUSION: Understanding disease course improves prognostication, allowing for better-informed decisions about care.

Advance planning in end-of-life care: legal and ethical considerations for neurologists.

Neurological illnesses can leave patients unable to make legally valid decisions about their medical treatment. However, this loss of decision making capacity can often be predicted in advance. The law in the UK now enables patients to make legally binding arrangements to either refuse specific treatments in advance or to appoint others to make decisions on their behalf. This article discusses the mechanics of advance planning under UK law and the role of the neurologist in helping patients to plan ahead.

Determining medical decision-making capacity in brain tumor patients: why and how?

BACKGROUND: Brain tumor patients are at high risk of impaired medical decision-making capacity (MDC), which can be ethically challenging because it limits their ability to give informed consent to medical treatments or participation in research. The European Association of Neuro-Oncology Palliative Care Multidisciplinary Task Force performed a systematic review to identify relevant evidence with respect to MDC that could be used to give recommendations on how to cope with reduced MDC in brain tumor patients. METHODS: A literature search in several electronic databases was conducted up to September 2019, including studies with brain tumor and other neurological patients. Information related to the following topics was extracted: tools to measure MDC, consent to treatment or research, predictive patient- and treatment-related factors, surrogate decision making, and interventions to improve MDC. RESULTS: A total of 138 articles were deemed eligible. Several structured capacity-assessment instruments are available to aid clinical decision making. These instruments revealed a high incidence of impaired MDC both in brain tumors and other neurological diseases for treatment- and research-related decisions. Incapacity appeared to be mostly determined by the level of cognitive impairment. Surrogate decision making should be considered in case a patient lacks capacity, ensuring that the patient's "best interests" and wishes are guaranteed. Several methods are available that may help to enhance patients' consent capacity. CONCLUSIONS: Clinical recommendations on how to detect and manage reduced MDC in brain tumor patients were formulated, reflecting among others the timing of MDC assessments, methods to enhance patients' consent capacity, and alternative procedures, including surrogate consent.

Mental incapacity in patients undergoing neuro-oncologic treatment: a cross-sectional study.

OBJECTIVE: To evaluate the prevalence of mental incapacity to make neuro-oncologic treatment decisions and to identify patients likely to experience difficulty with medical decision-making to enable a more rigorous and focused assessment. METHODS: The preoperative mental capacity to give valid consent to neurosurgery of 100 patients with radiologically suspected intracranial tumors was assessed. Mental capacity was formally assessed using the MacArthur Competence Assessment Tool for Treatment (MACCAT-T) conducted by a dual-qualified physician and lawyer. To assess the relationship between cognition and mental capacity, cognitive function was assessed after the MACCAT-T interview using the Addenbrooke's Cognitive Examination-revised (ACE-R). Decisions about capacity made by the assessor were compared with the informal assessment of capacity of the neurosurgical team. RESULTS: Of 100 patients, 25 were identified by the assessor as lacking the necessary mental capacity to give valid consent to neurosurgery. Mental incapacity was most common among patients with World Health Organization grade IV tumors (38%) and was more common in men than women (36% of men lacked capacity vs 14% of women). Patients lacking mental capacity were significantly more cognitively impaired than those with capacity (median [interquartile range (IQR)] total ACE-R of 44 [0, 65.5] for incapable patients compared with a median [IQR] total ACE-R score of 88 [82, 95] for patients with capacity). Of 25 patients found to lack capacity by the assessor, 13 (52%) were identified as lacking capacity by the neurosurgical team and were treated under the provisions of the Adults with Incapacity (Scotland) Act 2000. A score of <4/7 in the semantic verbal fluency subset of the ACE-R (naming up to 10 animals in 1 minute) was predictive of incapacity (96% sensitivity, 63% specificity). CONCLUSIONS: Mental incapacity in patients with intracranial tumors is common and is underestimated by clinicians seeking consent for neuro-oncologic treatment. Cognitive impairment is associated with incapacity. We propose a simple, brief cognitive screening test to identify patients who warrant a more rigorous interrogation of their mental capacity as part of the process of seeking consent for neuro-oncologic treatment.