Neurocognitive Deficits and Neurocognitive ...

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Opinion statement. Neurocognitive deficits are common with brain tumors. If assessed at presentation using detailed neurocognitive tests, problems are detected ...
Curr Treat Options Neurol (2016) 18:22 DOI 10.1007/s11940-016-0406-5

Neuro-oncology (R Soffietti, Section Editor)

Neurocognitive Deficits and Neurocognitive Rehabilitation in Adult Brain Tumors Julia Day, BSc (Hons), MScR1 David C. Gillespie, MA (Hons), ClinPsyD, PhD, MSc (Fam Therapy), CPsychol1 Alasdair G. Rooney, MBChB, MD2 Helen J. Bulbeck, PhD3 Karolis Zienius, MBChB, BSc4 Florien Boele, PhD4 Robin Grant, MBChB, MD4,* Address 1 Department of Clinical Neuropsychology, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, Scotland, UK 2 Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, Scotland, UK 3 Brainstrust (the brain cancer people), Yvery Court, Castle Road, Cowes, Isle of Wight, PO31 7QG, UK *,4 Edinburgh Centre for Neuro-Oncology, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, Scotland, UK Email: [email protected]

* Springer Science+Business Media New York 2016

This article is part of the Topical Collection on Neuro-oncology Keywords Neuro-rehabilitation I Neurocognitive I Brain tumor I Fatigue I Depression

Opinion statement Neurocognitive deficits are common with brain tumors. If assessed at presentation using detailed neurocognitive tests, problems are detected in 80 % of cases. Neurocognition may be affected by the tumor, its treatment, associated medication, mood, fatigue, and insomnia. Interpretation of neurocognitive problems should be considered in the context of these factors. Early post-operative neurocognitive rehabilitation for brain tumor patients will produce rehabilitation outcomes (e.g., quality of life, improved physical function, subjective neurocognition) equivalent to stroke, multiple sclerosis, and head injury, but the effect size and duration of benefit needs further research. In stable patients treated with radiotherapy +/− chemotherapy, the most frequent causes of distress include neurocognitive problems, psychological factors of anxiety, depression, fatigue, and sleep.

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Exercise, neurocognitive training, neurocognitive behavioral therapy, and medications to treat fatigue, behavior, memory, mood, and removal of drugs that may be associated with neurocognitive side effects (e.g., anti-epileptic drugs) all show promise in helping patients to manage the effects of their neurocognitive impairments better. As these are complex symptoms, multidisciplinary expertise is necessary to evaluate the influence of each variable to plan appropriate support and intervention. Neurocognitive rehabilitation should therefore occur in parallel with disease-centered, medical management from the outset. It should not occur in series, as a restricted phase in a patient’s pathway. It should be considered in the pre- and post-operative period where there are good prospects of recovery, as one would for any brain-injured patient, so that the person may reach their optimal physical, sensory, intellectual, psychological, and social functional level. Yet the identification and selection of patients for early neurological rehabilitation and routine evaluation of cognition is uncommon in neurosurgical wards.

Introduction Brain cancer is different from other cancers; not only do patients and their carers have to come to terms with the diagnosis of brain cancer, but they do so in the knowledge that this diagnosis will certainly mean progressive neurological and cognitive deficit. Lehman et al. [1] acknowledge that in 80 % of central nervous system tumors, there is a need for rehabilitation due to physical or cognitive impairment while approximately 20 % have seizures only [2]. As it is, brain cancer-associated morbidity is multifaceted and largely under-recognized. In the UK, there are over 60,000 people living with a brain tumor diagnosis [3]. It is one of the most lethal diseases; only 27 %

of people treated for glioblastoma will be alive at the end of the second year following diagnosis [4]. At 5 years, this drops to 9.8 %. The average number of years of life lost to a brain tumor is 20.1, compared to breast at 13.5 [5]. Most patients (995 %) will have physical, sensory, intellectual, psychological, or social problems at diagnosis. Survival rates vary from weeks to several years, depending on the tumor grade. Neurocognitive rehabilitation should occur in parallel with disease-centered, medical management from the outset. It should not occur in series, as a restricted phase in a patient’s pathway [6••].

What are the neurocognitive and neurological issues for brain tumor patients, including pre- and post-neurosurgery? There are currently no agreed national referral criteria for neuro-rehabilitation for patients with brain tumors. Realistically, patients with glioblastoma (WHO grade 4), or brain metastases, who have limited treatment options because of poor clinical or molecular prognostic factors and serious comorbidities (Table 1), or where neurocognitive deficits do not improve with steroids are more suitable for early palliative referral rather than rehabilitation. However, for patients where there are treatment options with expectations of a good response and who are considered to have a good prognosis, neurological and neurocognitive rehabilitation is warranted, where there are disabilities. Over 80 % of patients who have radiotherapy describe neurocognitive impairments, such as mental slowing and short-term memory loss [7–9]. Longitudinal studies have found that these are progressive across several domains [10–12].

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Page 3 of 16 22 These considerations apply to the following:

& & & & &

Varying survivorship Variable trajectory, even for benign brain tumor diagnoses High frequency and severity of disabling complications Knowledge of increasing neurocognitive dysfunction Life context—where there is a lack of resilience or ability to cope Mukand [8] identified the following neurological complications in brain tumor inpatients:

& & & & & & & & & & &

Cognitive deficits 80 % Weakness 78 % Visual-perceptual deficit 53 % Sensory loss 38 % Bowel/bladder 37 % Cranial nerve palsy 29 % Dysarthria 27 % Dysphagia 26 % Aphasia 24 % Ataxia 20 % Diplopia 10 % Seventy five percent of inpatients will have three or more of these neurological complications; 39 % will have five or more. Catt et al. [13] identified that supportive care pathways for patients and their families differ between hospitals; guidelines either omit important aspects of care and follow-up or are based on assumptions with little empirical support; as treatments of patients is often palliative, more efforts are needed to ensure good continuity of care; current follow-up is failing to meet the psychological needs of patients and their caregivers; and there is a need for developing innovative and integrated interventions that effectively support caregivers, such as proactive counseling.

Table 1. Factors to consider when considering long-term prognosis Factors

Good prognosis

Poor prognosis

Age (years) KPS Size Site Grade Type Molecular markers (a) MGMT (b) Ch1p19q (c) IDH Surgery Comorbidity

G40 80–100 G3 cm Non-dominant cortical/frontal WHO 1–3 Oligodendroglioma

970 G60 96 cm Dominant deep seated/bilateral WHO 4 Astrocytoma

Methylated Deleted Mutant Complete resection Nil

Non-methylated Non-deleted Wild type Biopsy only Several/serious

KPS Karnofsky Performance Score, WHO World Health Organization, MGMT methyl guanine methyl transferase, Ch1p19q hetero-zygosity at chromosome 1p19q in tumor, IDH iso-citrate dehydrogenase mutation status

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In most neurosurgical centers, there are several barriers to the routine identification of neurocognitive impairment and referral for neurocognitive rehabilitation. These include the following:

&

Shorter neurosurgical admission periods with focus on efficient throughput and waiting times & Neurocognitive difficulties not appreciated by staff or staff have too little time to assess [14••] & Lack of routine neurocognitive screening at surgical admission & Mood-related difficulties (anxiety and depression) are considered a normal reaction and referrals are not made for support [15] & Uncertainty as to whether patients would be accepted by neurorehabilitation by specialist services, or what the referral criteria are & The wait for rehabilitation referral may delay surgical discharge & Lack of awareness of availability of community neurocognitive rehabilitation services & Lack of resource for the delivery of outpatient neurocognitive or psychological support resulting in delayed opportunities & The perception that patients may be too tired during radiotherapy +/− chemotherapy to cope with, or benefit from, early rehabilitation. & Not the patient’s priority - early in their recovery (a) Pre-surgery neurocognitive neurological deficits Cognitive or personality change is rarely the sole presenting symptom in patients with brain tumors. However, at hospital presentation, personality change or cognitive deficits are recorded in between 10 and 30 %, respectively [3]. Where cognitive problems are identified, fewer than two thirds of patients complain of these symptoms. Although patients may be uncomplaining, family members are usually very aware of changes in personality, behavior, memory, or neurocognitive ability. Where present and severe, these problems may also have implications for treatment. Capacity to give consent for surgery requires function across four cognitive domains: understanding, retaining, evaluating information in order to make a decision, and communicating that decision. The patient’s ability to do so may be compromised by neurocognitive impairment arising from the brain tumor. Indeed, using the MacArthur Competence Assessment Tool (MacCAT-T) in 100 neurosurgical patients with radiologically suspected intracranial tumors, incapacity to give informed consent was found in a strikingly high proportion (25 %, compared with 13 % identified by the neurosurgeon [14••]. Cognitive assessment using the Addenbrooke’s Cognitive Examination—revised (ACE-III) revealed significantly greater neurocognitive impairment (median ACE-R 54/100) in patients lacking capacity, compared to those with capacity (median ACE-R 88/100). Neurocognitive deficits were more common in malignant tumors (Fig. 1). The authors concluded that a short test of semantic verbal fluency—Bhow many animals can you think of in 60 s^ is helpful as a screening test for cognition: a total of G15 named animals suggesting the need for

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Fig. 1. Addenbrooke’s cognitive examination scores in pre-operative patients with brain tumors

more detailed cognitive screening and ≤10 suggesting more detailed assessment of capacity is required [16]. (b) Post surgical cognitive neurological deficits Following resection of tumor located in the frontal/temporal areas, 950 % of patients will experience new or worsening post-surgical neurocognitive/language disturbance [17]. Most deficits significantly improve, or resolve, between 7 days and 3 months [18]; however, some deficits remain at 1 year [19]. In addition, deficits in memory, attention, and executive function, are frequently reported in the immediate post-operative phase and often persist beyond the 3 months [19, 20]. Cofactors such as epilepsy, anti-epileptic drugs (AEDs), corticosteroids, and mood may affect neurocognition and behavior. AEDs have a significant negative effect on attention and information processing [21]. Peri-operative corticosteroids improve cognition [22], but there is evidence of the detrimental effect of long-term corticosteroids [23]. Psychological and psychiatric problems are common postoperatively—clinically diagnosable major depressive disorder affects approximately 10 % of patients at any given time [24••].

Why and how do we objectively assess neurocognitive function? Accurate assessment of neurocognitive status is essential as early as possible after diagnosis. Assessment helps patients and caregivers to understand current

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Curr Treat Options Neurol (2016) 18:22 neurocognitive strengths and weaknesses, which is important for the emotional adjustment of the person living with a brain tumor, and helps families understand what the patient can and cannot do. Informed decisions can then be made about key life situations such as the level of support required for the patient to maintain maximum independence, and the timing of any return to work. For those patients who access rehabilitation, knowledge of neurocognitive strengths and weaknesses is used to select appropriate rehabilitation goals. Neurocognition can be assessed objectively using standardized, norm-based assessments in either pen-and-paper or computerized formats, or subjectively by asking for the patient’s views of their own neurocognitive functioning or the opinions of family caregivers. Assessment of both objective and subjective domains is required to obtain a comprehensive overview of a patient’s neurocognitive abilities. Objective assessment can be carried out using either a neurocognitive screening test, or by administering a longer, more detailed neuropsychological assessment. Both approaches have strengths and limitations.

(a) Screening tools The most widely used screening tools of neurocognitive functioning—in order of increasing item number—are the Mini-Mental State Examination (MMSE) [25], the Montreal Cognitive Assessment (MoCA) [26], and the Addenbrooke’s Cognitive Examination (ACE) [27]. Screening tools have the advantage of brevity, require relatively little in the way of specialist knowledge to administer, and can be completed when patient motivation is low, mood is depressed, or fatigue is present. Even the very brief MMSE has been shown to be predictive of survival in glioma [28]. If it is believed that the patient’s continued state is due to neurological changes resulting in apathy, fatigue and depression then it may be appropriate to screen to make treatment goals that could have a subsequent impact on these conditions. However, neurocognitive screening tools have significant limitations. Although there can be little doubt that neurocognitive impairment exists when a patient performs in the abnormal range on a screening tool, impairment is not necessarily ruled out when scores fall in the so-called Bnormal^ range. This is particularly true if neurocognitive problems are more subtle or experienced in a limited number of neurocognitive domains [29]. As an example, Robinson et al. [30] found that whereas 30 % of brain tumor patients were impaired on the MoCA, 70 % were impaired in one or more neurocognitive domains when more detailed assessments were conducted. Executive functioning deficits are most likely to be overlooked given the small number of items that address this neurocognitive domain in most screening tools. This is of particular concern because executive functioning deficits have been shown to occur in approximately 40 % of patients with temporal lobe glioma and are predictive of occupational and recreational functioning [31].

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(b) Neurocognitive test batteries The International Cognition and Cancer Task Force have recommended the specific neurocognitive tests that should be administered to patients with non-CNS cancers [32], and these tests are no less appropriate for patients with brain tumors (for a review, see [9]). The core battery of validated neuropsychological tests comprises measures of processing speed and executive function (Trail Making Test; TMT, [33]; learning and memory (Hopkins Verbal Learning Test-Revised; HVLT-R, [34]; visuospatial functioning (Benton’s Judgment of Line Orientation Test; [35]; and verbal fluency (Controlled Oral Word Association Test; COWA, [36]. A test of working memory is also recommended, e.g., digit span [37]. These tests allow for more comprehensive assessments of cognitive strengths and weaknesses, and can be supplemented by additional measures in a flexible, hypothesis-driven way. Parallel versions exist for some of the tests outlined above, controlling for practice effects when patients receive follow-up testing. Neurocognitive test batteries should, however, only be administered and interpreted by practitioners with adequate training. Limb weakness and visual impairments are common in brain tumor patients and may affect paper and pencil neuropsychological tests or those requiring the processing of visual information, and therefore, alternatives should be used in order to determine reliable performance on cognitive tasks.

Subjective assessment of cognitive functioning Subjective reports of cognitive functioning provide information about the types of everyday problems that patients or their family caregivers attribute to their neurocognitive deficits. Indeed, subjective neurocognitive symptoms are among the most common problems reported by patients with brain tumors [7]. The 6-item Cognitive Functioning Scale (CFS) from the Medical Outcomes Study (MOS) [38] has been used to measure the frequency of self-reported neurocognitive complaints in several brain tumor studies [39••, 40]. Some caution is required when interpreting subjective measures. Correlations between subjective and objective neurocognitive measures have been reported to be very low in a recent brain tumor study, with subjective cognitive deficits more closely related to self-reported mental health symptoms than tumor-related variables [41]. Nevertheless, subjective data are of value to clinicians. Patients who have many objective neurocognitive deficits but few subjective concerns may have poor insight into their condition and not see the need to engage in neurocognitive rehabilitation.

Associated factors affecting neurocognition (a) Fatigue Fatigue is defined as Ba distressing, persistent, subjective sense of physical, emotional, and/or cognitive tiredness or exhaustion related to cancer or cancer

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treatment that is not proportional to recent activity and interferes with usual functioning^ (NCCN). The prevalence of fatigue in the primary brain tumor population ranges between 25 and 90 % [42–44]. Fatigue can affect interpretation of neurocognition in several ways including poor compliance with tests, lack of effort during neurocognitive evaluations and attention deficits. Radiotherapy is the most consistent factor associated with fatigue [43, 45]. Medications to treat epilepsy, pain, nausea, brain edema, endocrine dysfunction, and physical impairment may also contribute to the fatigue presentation [46–48]. Limited evidence exists specifically exploring the effectiveness of interventions for post-radiotherapy fatigue; however, there is supportive evidence in the wider brain tumor population. Clinical trials of the CNS stimulants methylphenidate and modafinil have found mixed results [49–51]; this may be confounded by the inclusion of non-fatigued patients. As brain tumor patients often experience fatigue alongside symptoms of neurocognitive impairment, depression, anxiety, sleep disturbance, and physical impairment, these additional factors may play a role in symptom generation and may also confound the effectiveness of drug response [42, 52]. Therefore, a multidisciplinary approach may offer the most appropriate method of treatment. (b) Depression Troublesome depressive symptoms are present in 16–39 % of cases, while clinical depression occurs in a median of 15 % of brain tumor patients [24••]. Clinical depression is most robustly associated with poorer neurocognitive and physical functioning, greater tumor size, and reduced quality of life. [53]. Additional sociodemographic risk factors for depression may include a history of prior depressive episodes, female patient sex, childhood adversity, low socioeconomic status, poor social support, being unmarried, and family history of major depression [54]. Depression matters in particular because it is a predictor of completed suicide, the risk of which is markedly raised in the first 12 weeks after a diagnosis of CNS cancer [55]. Many tools exist for screening patients for depressive symptoms. Two have been partially validated in patients with brain tumor: the Hospital Anxiety and Depression Scale [56] (depression subscale, HAD-D at a threshold of 8+) and the Patient Health Questionnaire-9 (PHQ-9, at a threshold of 10+) [15, 57]. All patients who screen highly require further assessment to diagnose clinical depression. However, it can be difficult to determine whether particular symptoms are due to depression, a natural reaction to terrible circumstances, or to brain tumor treatments. Experienced consultation-liaison or neuropsychiatric review is indicated where possible. In addition, assessment of suicide risk is essential in all cases [24••]. The mainstay of treating clinical depression in otherwise healthy adults is an antidepressant [58]. It is not known, however, whether antidepressants are similarly effective in the presence of a brain tumor [59]. Systematic reviews conducted in other neurological populations

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suggest that antidepressants have a small but significant treatment effect [60]. In patients with other kinds of cancer the impact of antidepressant treatment is unclear and treatment decisions are recommended to occur on a case-by-case basis [61]. Antidepressant medication (excepting bupropion), when given in therapeutic doses, do not cause an increased risk of seizures in depressed but otherwise healthy adults [62]. Their impact on seizure threshold in brain tumor patients is not known, but untreated depression is itself a risk factor for epilepsy [63]. In practice, an SSRI is often prescribed as first-line treatment for clinical depression. Patients should be kept under regular review [64]. A cautious approach (e.g., starting at half the usual dose and increasing slowly under review) may be appropriate. The median duration of a treated episode of clinical depression in the community is approximately 3 months [65]. In longitudinal studies, depression in brain tumor patients can persist for at least 6 months in some individuals [66]. However, effectively treating clinical depression is likely to benefit the patient’s engagement with other components of neuro-rehabilitation (Table 2). (c) Drowsiness and sleep Drowsiness and sleep disorders are common symptoms in the oncology population in general, and are found in over 60 % with underlying CNS malignancy [67, 68]. Anything affecting alertness will impair neurocognition and performance and interpretation of neurocognitive tests. Somnolence is a frequent sub-acute adverse effect of cranial irradiation [45, 69]. It is present in up to 70 % of patients [69, 70] and even higher for those with brain tumors involving the hypothalamus, thalamus, and brainstem [71]. Solmnolence may be a result of insomnia, disruption to the circadian rhythm in addition to sleep fragmentation due to anxiety, depression, or sleep disordered breathing [72]. Insomnia is one of the most frequently reported symptoms of sleep disorders in adult neurology patients [73]. It is hypothesized to be as a result of altered melatonin kinetics caused by radiation therapy [74••]. There is limited literature on the effectiveness of interventions to improve sleep in neuro-oncological patients. Focus on sleep hygiene must Table 2. Clinical tips on rehabilitation of depressed patients The HAD-D (threshold 8+) or PHQ-9 (threshold 10+) can be used as screening tools to identify high-risk brain tumor patients requiring further assessment. Clinical depression should be formally diagnosed by clinical interview. An SSRI antidepressant is first-line treatment where indicated. BStart low, go slow,^ with regular review. Avoid bupropion in brain tumor patients unless there is a clear clinical indication for its use. Non-pharmacological treatments (e.g., CBT) may be effective in selected patients. Depression may solve or persist for up to at least 6 months in some cases. Seek specialist neuropsychiatric or consultation-liaison input where necessary.

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be emphasized and is recommended by the American Academy of Sleep Medicine [75]. In a recent meta-analysis [76], neurocognitive behavior therapy was found to be effective in reducing chronic insomnia by reduction of perpetuating factors and deconditioning the hyperarousal response. Muller et al. [77] investigated an effect of melatonin and found improvement in subjective and objective daytime sleepiness in obese patients with previously treated childhood craniopharyngioma. A number of pharmacological therapies are approved for the treatment of insomnia; however, none of them have yet been tested in oncological patients.

Treatment options for neurocognitive problems in people living with a brain tumor Treatment options encompass cognitive rehabilitation, pharmacology, and supportive management. Neurocognition programs vary. Some involve a team of therapists, such as psychologists, speech therapists, and neurocognitive training specialists, delivering intensive and holistic (whole person) programs, lasting for long intense periods. Other neurocognitive rehabilitation programs may be less demanding. Before starting neurocognitive rehabilitation, patients should be medically stable and have sufficient physical and mental strength to manage the requirements of a therapy program. Neurocognitive exercises to improve thinking and reasoning skills may involve identifying the key points in a paragraph, reviewing facts in it and drawing conclusions or to improve planning, or organizing a set of instructions. There is evidence that both postoperative computerized neurocognitive rehabilitation training programs and programs given in stable patients following treatment have a positive effect on memory and executive function [39••, 78, 79]. Neurocognitive rehabilitation and activity of daily living gains are influenced by the level of neurocognitive impairment at baseline and attention deficit after 4 weeks of focused neurocognitive rehabilitation. The gains achieved are comparable to patients following a stroke [78].

Cognitive interventions post treatment As anti-cancer treatments become more effective and available, patients live longer disease-free, but with long-term sequelae of the disease and the neurotoxic effects of treatment. Neurocognitive difficulties following radiotherapy are common [39••, 51, 80]. Several authors have recently proposed a Bcore set^ of data that are important to collect, as they contribute to symptom burden in patients previously treated for brain tumors. These are as follows: difficulty remembering, fatigue, distress (anxiety and depression), drowsiness, and difficulty with sleeping [81]. In a Cochrane systematic review, Khan et al. [82••] reviewed the effectiveness of multi-disciplinary rehabilitation following treatment of a brain tumor. One eligible RCT described improvements in self-reported neurocognitive function following intensive 3 × 1 h sessions of occupational, social, psychological, and physiotherapy rehabilitation three times per week for 6 to 8 weeks

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[83]. Two reviews of neurocognitive deficits in brain tumor patients [9, 39••] have also identified observational studies that have explored neurocognitive rehabilitation. RCTs have shown benefits with early post-surgical cognitive rehabilitation in visual attention and verbal memory, and in the stable posttreatment phase, benefits in attention, verbal memory and mental fatigue still persist at 6 month post cognitive rehabilitation [39••, 79, 84]. Day et al. [85] carried out a Cochrane systematic review to investigate interventions for neurocognitive deficits during or following cranial irradiation. Five pharmacological and one non-pharmacological randomized study were eligible. The non-pharmacological study investigated a neurocognitive rehabilitation and problem-solving program in 19 brain tumor patients undergoing radiotherapy [86]; although positive feedback was provided, no statistical analyses were carried out. During radiotherapy, one pharmacological study [87] supported the use of memantine, whereas the use of D-threo-methylphenidate [49] was inconclusive, with high attrition and risk of bias. Following radiotherapy, two studies [49, 87] offered preliminary findings for the use of modafinil and methylphenidate; however, studies were limited by small sample sizes and high risk of bias [51].

The role of coaching Patients and family caregivers live with their condition 24/7 and only spend a fraction of time visiting clinical experts; so, having the knowledge, skills, and confidence to manage one’s own health is strongly related to a positive range of health-related outcomes [88]. Qualitative studies [89, 90] show that some patients and the majority of caregivers want to be fully involved in understanding their illness, exploring their options for treatment and for living with the illness, sourcing information, knowledge, help, and advice. Coaching as an intervention increases activation, improving engagement and outcomes and is an important factor in helping patients to manage their health. Tailoring service delivery according to patient activation levels maximizes productivity and efficiency by ensuring that the level of support provided is appropriate to the needs of the individual. Caregivers identify dramatic changes in mood and neurocognition, as well as decreased ability to function independently [86, 91, 92]. Through coaching, playing a more collaborative role and being part of a group, psychosocial, neurocognitive, and functional outcomes for patients diagnosed with a brain tumor can be improved [93–96]. Patients and caregivers have more capacity to take control of their situation to secure the best possible outcomes; by being empowered through coaching they achieve greater autonomy, a better quality of life, improved neurocognition, and more satisfaction. They are better able to manage the interventions and to optimize the opportunities that they have.

Recommendations In our opinion, the local surgical team should take responsibility for identification, screening evaluation, and referral of patients for more detailed assessment. They should do the following:

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(a) Ask relatives whether there have been behavioral, neurocognitive or mood issues prior to admission. (b) Screen for neurocognition/capacity pre-operatively as a minimum. (c) Consider the most likely trajectory based on pre and post-operative prognostic factors (rehabilitation or palliative care). (d) Where a good prognosis is suspected, and there is evidence of neurocognitive disability, early referral by neurosurgery to neuropsychology for evaluation and treatment. (e) All patients to have access to coaching support through the treatment trajectory, to enable them to optimize and manage interventions. (f) Where patients have more severe and multiple neurological rehabilitation needs including neurocognitive problems, transfer to specialized inpatient or to outpatient community services may be required. (g) For patients where treatment options are limited, early psychological, coaching and supportive palliative care referral would be justified. After completion of oncological treatment, and possibly at planned annual visits, the oncology team should take responsibility to screen the patient and caregiver to identify their main concerns. Based on the outcomes of the screening evaluation, more detailed assessments should direct appropriate interventions. These may include more detailed tests of neurocognition, patient and caregiver questionnaires to assess subjective neurocognitive concerns of patient, mood, fatigue, sleep, and medication for epilepsy and depression. Neurocognitive tests may also help to establish whether neuropsychology referral is required. Neuropsychologists would be the appropriate clinician to coordinate rehabilitation at this point. Depending on the resources available and special interest of the centers, a multi-disciplinary meeting with expertise in, neurology, neuropsychology, clinical psychology, clinical oncology, psychiatry, neuro-rehabilitation, coaching, and sleep may be a valuable model. The evidence supports the value of neurocognitive therapies, either face to face or online in patients, capable of benefitting from the treatment. Coaching of patients and family caregivers during this period would help to maintain involvement, compliance with treatment and engagement with family. Commercial delivery of online neurocognitive assessments of memory, reasoning, concentration and planning online is increasingly common (www. cambridgebrainsciences.com). Follow-up care of neuro-oncology is likely to change with increasing use of video and mobile technology. There is increasing interest in engaging with formal neurological rehabilitation services and working on guidelines for referral. Equally, rapid access to appropriate levels of supportive and palliative care is required for those patients with shorter prognosis CNS tumors. Collaboration between health and social care is required to develop appropriate placements for those people who need ongoing institutional care for challenging symptoms where support in the community is not practical.

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Compliance with Ethical Standards Conflict of Interest Julia Day, David C. Gillespie, Alasdair G. Rooney, Helen J. Bulbeck, Karolis Zienius, Florien Boele, and Robin Grant declare that they have no conflict of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: •• Of major importance 1.

Lehmann J, De Lisa J, Warren C. Cancer rehabilitation assessment of need development and education of a model of care. Arch Phys Med Rehabil. 1978;59:410–9. 2. Grant R. Overview: brain tumour diagnosis and management/Royal College of Physicians guidelines. J Neurol Neurosurg Psychiatry. 2004;75:18–23. 3. brainstrust. Living with a brain tumour. Prevalence of intracranial tumours - September 2013. [Internet]. Available from: bit.ly/brain_tumour_infographic. 4. Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96. 5. Burnet NG, Jefferies SJ, Benson RJ, Hunt DP, Treasure FP. Years of life lost (YLL) from cancer is an important measure of population burden and should be considered when allocating research funds. Br J Cancer. 2005;92(2):241–5. 6.•• Wade D. Rehabilitation—a new approach. Overview and part one: the problems. Clin Rehabil. 2015;29D11]:1041–50. This paper emphasizes the importance of early rehabilitation following brain injury for any cause. 7. Lidstone V, Butters E, Seed PT, Sinnott C, Beynon T, Richards M. Symptoms and concerns among cancer outpatients: identifying the need for specialist palliative care. Palliat Med. 2003;17:588–95. 8. Mukand JA, Blackinton DD, Crincoli MG, Lee JJ, Santos BB. Incidence of neurologic deficits and rehabilitation of patients with brain tumors. Am J Phys Med Rehabil. 2001;80(5):346–50. 9. Taphoorn MJB, Klein M. Cognitive deficits in adult patients with brain tumours. Lancet Neurol. 2004;3:159–68. 10. Chang EL, Wefel JS, Hess KR, Allen PK, et al. Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus wholebrain irradiation: a randomized controlled trial. Lancet Oncol. 2009;10:1037–44.

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Gondi V, Mehta MP, Pugh S. Memory preservation with conformal avoidance of the hippocampus during whole brain radiotherapy for patients with brain metastases: primary endpoint results of RTOG 0933. Int J Radiat Oncol Biol Phys. 2013;87(5):1186. 12. Welzel G, Fleckenstein K, Schaefer J, Hermann B, et al. Memory function before and after whole brain radiotherapy in patients with and without brain metastases. Int J Radiat Oncol Biol Phys. 2008;72:1311–8. 13. Catt S, Chalmers A, Critchley G, Fallowfield L. Supportive follow up in patients treated with radical intent for high grade glioma. CNS Oncol. 2012;1(1):39–48. 14.•• Kerrigan S, Erridge S, Liaquat I, Graham C, Grant R. Mental incapacity in patients undergoing neuro-oncologic treatment: a cross-sectional study. Neurology. 2014;83D6]:537–41. This paper examines the relationship between capacity to give consent for surgery and cognitive testing and the value of the verbal fluency test Danimals] in identifying patients that require more detailed assessment. 15. Rooney AG, McNamara S, Mackinnon M, Fraser M, Rampling R, Carson A, et al. Screening for major depressive disorder in adults with cerebral glioma: an initial validation of 3 self-report instruments. NeuroOncology. 2013;15(1):122–9. 16. Kerrigan S, Rooney A, Grant R. Measuring cognitive function in people with brain tumours using the Addenbrooke’s cognitive examination. J Neurol Neurosurg Psychiatry. 2012;83:1. 17. Davie GL, Hutcheson KA, Barringer DA. Aphasia in patients after brain tumor resection. Aphasiology. 2009;23(9):1196–206. 18. Finch E, Copland DA. Language outcomes following neurosurgery for brain tumours: a systematic review. NeuroRehabilitation. 2014;34:499–514. 19. Satoer D, Visch-Brink E, Smits M, Kloet A, Looman C, Dirven C, et al. Long-term evaluation of cognition after glioma surgery in eloquent areas. J Neurooncol. 2014;116:153–60.

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