Prospective analysis of neuropsychological deficits

CLINICAL ARTICLEJ Neurosurg 127:1242–1248, 2017

MeningioMas have an incidence of 6 per 100,000, accounting for 13%–26% of all intracranial tu-mors.15,18 According to the classification of the

WHO, more than 90% of meningiomas are Grade I tu-mors, implying a benign clinical course.15 In general, initial treatment of these tumors includes resection, radiotherapy, or the so-called wait-and-scan approach, depending on the location and size of the tumors as well as the extent of neurological deficits.

To date, parameters such as mortality and grade of re-section have been the main focus as measures of success for resection. This focus has resulted in disregarding neu-rological and neuropsychological deficits and patient qual-ity of life for many decades, particularly in patients with meningiomas of the skull base. Advanced technology in diagnosis, surgical techniques, and performance has re-sulted in a considerable decrease in neurological deficits following resection of meningiomas.4,7 Nevertheless, due

ABBREVIATIONS EORTC = European Organization for Research and Treatment of Cancer; FM = figural memory; FSRT = fractionated stereotactic radiotherapy; GTR = gross-total resection; HAD-S = Hospital Anxiety and Depression Scale; HAWIE-R = Hamburger Wechsler Intelligence Test for Adults–Revised; IMRT = intensity-modulated radiotherapy; STR = subtotal resection; TMT-B = Trail Making Test, version B; VLMT = Verbal Learning and Memory Test; WMS-R = Wechsler Memory Scale, revised version.SUBMITTED July 27, 2016. ACCEPTED October 13, 2016.INCLUDE WHEN CITING Published online February 10, 2017; DOI: 10.3171/2016.10.JNS161936.* Drs. Schick and Unterberg share senior authorship of this work.

Prospective analysis of neuropsychological deficits following resection of benign skull base meningiomas*Klaus Zweckberger, MD, PhD, Eveline Hallek, Lidia Vogt, PhD, Henrik Giese, MD, Uta Schick, MD, PhD, and Andreas W. Unterberg, MD, PhDDepartment of Neurosurgery, University of Heidelberg, Germany

OBJECTIVE Resection of skull base tumors is challenging. The introduction of alternative treatment options, such as radiotherapy, has sparked discussion regarding outcome in terms of quality of life and neuropsychological deficits. So far, however, no prospective data are available on this topic.METHODS A total of 58 patients with skull base meningiomas who underwent surgery for the first time were enrolled in this prospective single-center trial. The average age of the patients was 56.4 ± 12.5 years. Seventy-nine percent of the tumors were located within the anterior skull base. Neurological examinations and neuropsychological testing were per-formed at 3 time points: 1 day prior to surgery (T1), 3–5 months after surgery (T2), and 9–12 months after surgery (T3). The average follow-up duration was 13.8 months. Neuropsychological assessment consisted of quality of life, depression and anxiety, verbal learning and memory, cognitive speed, attention and concentration, figural memory, and visual-motor speed.RESULTS Following surgery, 23% of patients showed transient neurological deficits and 12% showed permanent new neurological deficits with varying grades of manifestation. Postoperative quality of life, however, remained stable and was slightly improved at follow-up examinations at T3 (60.6 ± 21.5 vs 63.6 ± 24.1 points), and there was no observed effect on anxiety and depression. Long-term verbal memory, working memory, and executive functioning were slightly affected within the first months following surgery and appeared to be the most vulnerable to impairment by the tumor or the resection but were stable or improved in the majority of patients at long-term follow-up examinations after 1 year.CONCLUSIONS This report describes the first prospective study of neuropsychological outcomes following resection of skull base meningiomas and, as such, contributes to a better understanding of postoperative impairment in these patients. Despite deterioration in a minority of patients on subscales of the measures used, the majority demonstrated stable or improved outcome at follow-up assessments.https://thejns.org/doi/abs/10.3171/2016.10.JNS161936KEY WORDS skull base meningioma; resection; quality of life; neurocognitive functioning; neuropsychological assessment; oncology

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Neuropsychological outcome and removal of skull base meningiomas

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to improved comprehensive treatment modalities such as radiotherapy, and patients’ expectations of continuing an unrestricted private and professional life following tumor resection, neuropsychological functioning and quality of life have been brought to the forefront, particularly given the benign histology of these tumors.3

Complaints of neuropsychological deficits are com-mon at postsurgical follow-up and are particularly noted in relation to a patient’s ability to work. Despite these complaints, systematic neuropsychological assessments have been lacking in the clinic and the literature, which furthermore is contradictory on this topic. Tucha et al. showed that comparison of pre- and postoperative assess-ments of cognition revealed no differences, except in the case of working memory.28 The constructs investigated by Tucha and colleagues were memory, visuoconstructive abilities, and executive functions. Furthermore, postoper-ative improvement in attentional functions was observed in 54 patients.28 On the other hand, Dijkstra et al. reported on 89 patients who were matched to healthy controls and noted significant impairment in executive functioning, verbal memory, information processing capacity, psycho-motor speed, and working memory following resection of benign meningiomas.9 Interestingly, a subgroup analysis of patients with skull base meningiomas showed that these patients performed significantly worse on 3 of 6 neurocog-nitive domains compared with patients with meningiomas of the convexity.9

Surgical removal of skull base meningiomas is chal-lenging and, due to the tumor location at the skull base involving cranial nerves, vessels, and osseous structures, these surgeries are often associated with new postoperative neurological deficits. In light of improved radiotherapeutic strategies implementing single-fraction stereotactic radio-surgery, fractionated stereotactic radiotherapy (FSRT), or intensity-modulated radiotherapy (IMRT),6 a solitary ag-gressive surgical approach associated with neurological deficits is no longer acceptable. Hence, the favored treat-ment approach now tends toward a more thoughtful resec-tion focusing on the patient’s quality of life, along with adjuvant radiotherapy where tumor remnants have had to be left in critical locations, such as within the orbital fis-sure or the cavernous sinus.

In the current study, we prospectively investigated neu-ropsychological and neurological deficits before and up to 1 year after patients underwent resection of benign skull base meningiomas for the first time. Examining neurolog-ical deficits and assessing neuropsychological functioning, focusing on depression and anxiety, memory and cogni-tion, learning and attention, cognitive speed and executive functioning, as well as quality of life, will bring a better understanding regarding the situation patients are faced with following resection of skull base meningiomas.

MethodsPatient Characteristics and Study Design

A total of 58 patients who underwent skull base me-ningioma operations for the first time were enrolled con-secutively in this prospective single-center trial at our University hospital between 2009 and 2011. Participation

in this study was voluntary without exception, and did not affect any standard procedures regarding surgery, in-hos-pital course of treatment, or follow-up. The local stand-ing committee of ethical practice approved the protocol of this study and all patients provided written consent to participate.

Information was gathered from medical records about the patients, any comorbidities, the surgery and associated complications, as well as the in-hospital course of treat-ment. The average age of the patients in the study was 56.4 ± 12.5 years with a range of 29–75 years. The patient cohort showed a typical sex distribution for meningio-mas, with more females (4 to 1) in the cohort. To assess tumor size, location, and associations with neuroanatomi-cal structures, all patients underwent contrast-enhanced T1-weighted MRI prior to surgery and during follow-up examinations. The tumor size was quantified using axial MR images where the tumor showed maximal expansion, measuring the size in anterior-to-posterior and right-to-left directions. Seventy-nine percent of the tumors were located within the anterior skull base, including the cli-noid region, the lateral and medial sphenoid wing, and the sphenoorbital and olfactory region, whereas a smaller pro-portion were located within the middle or posterior skull base (Table 1).

Outcome MeasurementNeurological examinations and neuropsychological

testing were performed at 3 time points: 1) T1, 1 day prior to surgery; 2) T2, 3–5 months after surgery; and T3, 9–12 months after surgery. The average follow-up duration was 13.8 months. Following physical examinations by a neu-rosurgeon and after providing informed consent, patients were subjected to a battery of different neuropsychological tests, supervised by a neuropsychologist (L.V.), and also completed questionnaires regarding their quality of life.

TABLE 1. Distribution of tumor locations at the skull base

Dominant Location %

Anterior* Medial sphenoid wing 21 Sphenoorbital 14 Clinoid 12 Lateral sphenoid wing 9 Tuberculum sellae 9 Olfactory groove 7 Planum sphenoidale 7Middle Tentorium 5 Sella region 2 Cavernous sinus 2Posterior Petroclival 5 Foramen magnum 3 Os petrosum 2 Cerebellopontine angle 2

* Seventy-nine percent of all tumors were located within the anterior fossa.


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Motor and sensory deficits (such as palsies and crani-al nerve function) were investigated during neurological examination, in addition to gait, speech, and vertigo. We distinguished between transient and permanent deficits (defined to persist longer than 3 months postoperatively).

Neuropsychological assessment included verbal learn-ing and memory (the verbal learning and memory test [VLMT]), cognitive speed (the Hamburger Wechsler In-telligence Test for Adults–Revised [HAWIE-R]), attention and concentration (the Wechsler Memory Scale, revised version [WMS-R]), figural memory (FM; from the WMS-R), and cognitive flexibility (the Trail Making Test, ver-sion B [TMT-B]). These tests are so-called “standardized methods” that were normalized using healthy controls with the same ages as the study patients. Using these tests, the critical differences from the normalized values were investigated.

Verbal learning and memory function was quantified using the VLMT. This test is the German version of the Auditory Verbal Learning Test. This test measures short-term and long-term memory, asking participants to learn and recall words lists with and without distractions and with a delay of up to 30 minutes.12,22 Scoring and interpre-tation of this test includes correctly reported words, with points subtracted for incorrectly recalled words to obtain the final score.

In accordance with the Adult Intelligence Scale-R, the revised version of the HAWIE (HAWIE-R) assesses both general cognitive development and capacity and possible impairments in adults;34,35 this test encompasses verbal- and task-based portions. The Number and Symbol Test that we used here is part of the task-based section of the HAWIE test and provides information regarding psycho-motor speed and cognition capacity. The task involved referring to a number-symbol allocation scheme, with par-ticipants required to note the correct symbols of numbers less than 100 in a 90-second time period.

Impairments of cognition, attention, and concentration, as well as verbal and visual memory, are the most frequent problems found in patients with brain tumors.14,16,21, 29,32 In this study, we used 2 subtests on 13 available variables from the revised version of the WMS (WMS-R), empha-sizing both FM and attention/concentration.34 To quantify FM, patients were asked to recognize which of the pre-sented abstract patterns they had been shown previously. This task carried a maximum of 10 points. Concentration and attention were measured by asking participants to re-peat numbers of increasing length forward and backward. Participants could gain a maximum of 24 points over 2 rounds for this task.

The TMT is an internationally well-known test to measure attention, executive functioning, and cognitive speed.5,11,19,20,24,25,27 This test was developed by Reitan and Tarshes in 195923 and translated into a standardized Ger-man version. Divided into 2 parts, the TMT-A and TMT-B, this test requires patients to connect randomly distrib-uted numbers from 1 to 25 on a paper sheet (TMT-A) and also to connect numbers from 1 to 13 and letters from A to L (1-A-2-B-3-C-…, etc.; TMT-B) as fast as possible, with no time limit on the task. In previously performed studies to validate these tests, the TMT-B version showed

special sensitivity for executive functioning and cognitive speed.2,5,24

The term “quality of life” has become very popular in recent years. Because many factors are involved in how patients will assess their quality of life, including factors relating to their specific condition and the subjectivity of physical comfort, it is challenging to measure and quan-tify quality of life in different patients; in this study, we used the European Organization for Research and Treat-ment of Cancer (EORTC) QLQ-C30 questionnaire. This questionnaire was designed to examine cancer-specific quality of life and its changes over the time.8,26 Patients are required to answer 30 questions addressing 3 categories, to include general health condition, function, and symp-toms. To answer the questions, patients use scales ranging from 1 to 4 or 1 to 7, representing “very bad” to “excel-lent.” A higher score indicates better health and quality of life.1,10

To detect and measure anxiety and depression, we used the German version of the Hospital Anxiety and Depres-sion Scale (HAD-S) that was developed by Zigmond and Snaith in 1983.13,37 The test consists of 14 questions equal-ly distributed between assessing anxiety and depression. All questions are answered using scales ranging from 0 to 3 points expressing the intensity of anxiety or depression. The maximum score for each scale is 21 points, where a score of 0–7 points is considered normal, 8–10 indicates borderline anxiety or depression, and higher than 11 points indicates pathology.

Statistical AnalysesStatistical analyses were performed using a standard

SPSS statistics software package (version 20, IBM Corp.). Results are given as means, and a critical difference of more than 5% (p < 0.05) was assumed to be significant. Linear-transformed dependent data, such as quality of life, age, and tumor size, were tested for significance for all 3 time points using the Wilcoxon signed-rank test. Inde-pendent categorical variables from the neuropsychological data and the anxiety and depression scales were analyzed using the McNemar test and the Kappa test for concor-dance. We further used the chi-square test to evaluate relationships between the categorical variables for qual-ity of life, anxiety/depression, as well as the clinical and neuropsychological data (T1 to T2, T1 to T3). We used Pearson’s correlation coefficient to quantify the linear cor-relation between age and tumor size with quality of life and neuropsychological data, as well with anxiety and de-pression.

ResultsStudy Population

For this prospective single-center trial, 58 patients (47 female, 11 male) were recruited with an average age of 56.6 ± 12.5 years (range 29–75 years). All patients were undergoing their first surgery on a skull base meningioma. Patients with mental diseases and other severe comorbidi-ties that would prevent them from participating in the fol-low-up examinations were excluded. Seventy-nine percent of the tumors were located within the anterior skull base,




9% in the middle, and 12% in the posterior fossa. In 8% of cases tumors were not limited to 1 cranial fossa but were spread within 2 adjacent fossae. On average, tumors had a size of 38.4 ± 1.2 × 32.3 ± 1.3 mm on contrast-enhanced T1-weighted MR images.

At admission, 97% of all patients showed clinical symptoms caused by the lesions. The majority of patients were suffering from visual impairments (46%) and head-aches (31%), followed by irritation of the vestibulocochle-ar nerve (20%) causing hearing loss, vertigo, disturbances of balance, seizures (15%), impairments of the visual field (15%), and anosmia (13%).

ResectionThe grade of tumor resection was evaluated according

to Simpson’s criteria. Simpson Grades 1 and 2 were con-sidered gross-total resection (GTR), which was achieved in 49 patients (84.5%). Due to anatomical limitations of the skull base, such as tumor infiltration into the cavern-ous sinus or into the supraorbital fissure, subtotal resection (STR) was the outcome for 15.5% of surgeries (n = 9) to avoid severe neurological deficits. Histological examina-tion of the resected tumor tissue confirmed the diagno-sis of benign meningioma (WHO Grade I) in all patients. Subgroup analyses showed the tumors to be 59% transi-tional meningiomas, 24% meningiotheliomatous menin-giomas, 5% mixed forms, 5% fibroblastic, 2% choroid, and 2% secretory subtypes. In the remaining 3%, the subtype classification was not explicitly indicated.

To avoid further tumor progress, radiotherapy was ad-ditionally performed as an interval treatment 3 months af-ter surgery in 45% of patients (n = 4) with STR. Therefore, within the observation period, we could not detect signifi-cant tumor progress in any patient who required further surgery or radiotherapy.

Neurological OutcomeReferring to neurological deficits, we distinguished

between transient deficits after surgery and permanent deficits. Transient deficits were due to irritation of nerve function or brain tissue swelling with the potential for complete recovery and were, in most cases, not severe and only incompletely manifested. In total, 23% of all patients showed transient symptoms with varying grades of mani-festation (most patients had more than 1 symptom that was only partly manifested) and 12% had permanent deficits persisting for longer than 3 months. Within 3 months, the percentage of patients reporting deficits in cranial nerve function had declined from 24% to 8%, gait disturbances from 14% to 5%, and vision impairment from 10% to 5% (Table 2).

Neuropsychological OutcomeTo assess neuropsychological outcome we used a bat-

tery of different tests. Quality of life was quantified by the EORTC QLQ-C30. Prior to surgery, patients achieved an average of 60.6 ± 21.5 points, indicating an impact on quality of life by the tumor itself. Following surgery, and despite new postoperative neurological deficits, quality of life was not significantly affected (57.5 ± 22.2 points at

T2) but had recovered by the time of further follow-up ex-aminations (T3), reaching slightly higher levels than those noted preoperatively (63.6 ± 24.1 points).

Similar to the results on quality of life, resection did not appear to cause depression and anxiety in patients. In more than 90% of cases, patients showed stable results on the HAD-S scales, with only 1 patient showing signifi-cant improvement or deterioration across all time points (Table 3).

Verbal learning and memory function is a subcategory of cognition and was assessed using the VLMT. Short-term memory was not affected by surgery (T1: 47.3 ± 12.2 points; T2: 47.0 ± 11.4 points; T3: 48.7 ± 11.4 points). With respect to learning capacity, significant impairment was observed in 11% of patients between T1 and T2, but significant improvements were noted at long-term follow up assessments (T1 to T3) for 12% of patients and stable results observed for 79%. Therefore, in total 91% of pa-tients showed stable or improved verbal learning capacity within a 1-year follow-up (Table 4). In a subanalysis, how-ever, referring to long-term memory quantified by a test measuring performance after a temporal delay, a minor trend was found for unfavorable outcome throughout the

TABLE 2. Number and percentage of patients showing different neurological symptoms directly after surgery and 3 months after surgery

SymptomsPatients Directly After Surgery (%)

Patients 3 Months After Surgery (%)

Cranial nerve deficits 14 (24) 5 (8.6)Gait disturbances 8 (14) 3 (5)Vision impairment 6 (10) 3 (5)Double vision 6 (10) 2 (3.5)Palsy 3 (5) 1 (1.7)Vertigo 2 (3.5) 1 (1.7)Speech impairment 2 (3.5) —Sensory impairments 1 (1.7) —

Because some patients might have several different symptoms, they count for each measure.

TABLE 3. Depression and anxiety quantified using the HAD-S assessment

HAD-S Variable T1 to T2 (%) T1 to T3 (%)

Depression Significant improvement 7.5 3.5 Stable 90 90 Significant deterioration 2.5 6.5Anxiety Significant improvement 3 3.5 Stable 94 93 Significant deterioration 3 3.5

The table shows significant changes considering the time frames prior to and 3–5 months (T1 to T2) after surgery, as well as prior to and 9–12 months after surgery (T1 to T3). The majority of patients (> 90%) showed stable results regarding depression and anxiety.




entire observation period with limited recovery, but stable results in the follow-up examinations (T1: 9.1 ± 3.8 points; T2: 8.4 ± 3.3 points; T3: 8.8 ± 4.1 points) were observed. In these analyses, only 78% of patients remained stable or improved during follow-up examinations at T3.

Visual memory was assessed with the WMS-R/FM test. In contrast to verbal learning and memory function, visual memory slightly improved after surgery (T1: 6.1 ± 1.7 points; T2: 6.4 ± 1.7 points; T3: 6.5 ± 1.5 points). Tak-ing the full observation period into account (T1 to T3), 21% of patients showed significant improvements and 73% remained stable, with only a minority of 6% showing de-terioration (Table 4).

The number and symbols subtest of the HAWIE-R in-telligence test measures cognitive speed and concentra-tion. Following surgery, patients’ performance improved throughout the observation period from 39.9 ± 16.4 points (T1) to 40.4 ± 16.7 points, and further to 43.7 ± 15.4 points (T3). Taking the observation period as a whole (T1 to T3), 15% of patients showed significant improvements, 79% re-mained unchanged, and only 6% deteriorated.

Visuomotor processing speed and working memory were assessed using the TMT-B. Following surgery, the overall performance of all patients had nonsignificantly deteriorated from 99.5 ± 50.7 points at T1 to 95.2 ± 47.0 points at T2, and further to 86.6 ± 58.8 points at T3. In the acute postoperative period (T1 to T2), 56.5% remained unchanged or had significantly improved (28.2%), while 15.5% had significantly deteriorated. Looking at the lon-ger-term results (T1 to T3), 89% of patients were stable or had significantly improved, while only 11% showed re-maining significant impairments (Table 5).

Correlational analyses showed that age and tumor size did not influence quality of life prior to or after surgery (Wilcoxon signed-rank test). Similarly, no significant cor-relation was observed between preoperative neurological symptoms or location of the tumors and quality of life and cognition using chi-square analysis. However, a significant negative correlation was found between tumor size and cognitive speed, executive functioning, and memory using the Pearson correlation to compare pre- and postoperative performance, indicating that increased tumor size reduced ability in these areas. Similar negative correlations were found between age and recognition and cognition, also us-

ing the Person correlation to compare pre- and postoper-ative levels.

DiscussionResection of skull base meningiomas is challenging

and, particularly with the introduction of alternative or adjuvant treatment options such as radiotherapy, neuro-logical outcome and quality of life following surgery have become increasingly important in recent years.

Nevertheless, to our knowledge this is the first trial that uses a prospective design to analyze neurocognitive defi-cits and quality of life in patients following resection of benign skull base meningiomas. In this study, we exam-ined the quality of life, anxiety and depression, as well as cognitive function and speed prior to and up to 1 year after surgery.

In 1948, the WHO defined “health” as the presence of physical, mental, and social well-being with the absence of disease and infirmity.36 With this statement as a base, health-related quality of life can be defined as the extent to which one’s usual or expected physical, emotional, and social well-being are affected by a medical condition or treatment.17 In our patients, quality of life was already neg-atively affected prior to surgery by the tumor itself. Fol-lowing surgery, however, quality of life was only slightly and nonsignificantly impaired and further improved at follow-up examinations at 1 year. In accordance with our results, van Nieuwenhuizen et al. reported that the qual-ity of life in untreated patients with benign meningiomas (WHO Grade I) is, compared with healthy controls, sig-nificantly affected by lower psychomotor speed, work-ing memory capacity, and levels of self-perceived general health and vitality.31 Following surgery, Dijkstra et al. and van der Vossen et al. found that, in patients with menin-giomas at the convexity, information processing, psycho-motor speed, attention, verbal memory, and emotions are significantly affected.9,30 A subgroup analysis revealed that patients with skull base meningiomas showed even worse results.9 In our study we have observed that patients showed lower levels of performance in long-term verbal memory function, a subqualification of cognition, and in working memory speed within the first months follow-ing surgical removal of skull base meningiomas. In the long term, however, only a minority of patients showed persistent impairments. Referring to the entire observa-tion period (T1 to T3), the overall majority of patients has improved or remained stable on scores of short- and long-term verbal learning memory, visual learning, cogni-

TABLE 4. Verbal learning and visual learning memory as quantified by the VLMT and FM tests

Test T1 to T2 (%) T1 to T3 (%)*

VLMT Significant improvement 11 12 Stable 78 79 Significant deterioration 11 9FM Significant improvement 18 21 Stable 74 73 Significant deterioration 8 6

* More than 90% of patients showed improved performance or stable results within the entire observation period (T1 to T3).

TABLE 5. Visuomotor processing speed and working memory assessed using the TMT-B

TMT-B T1 to T2 (%) T1 to T3 (%)

Significant improvement 28 26Stable 56.5 63Significant deterioration 15.5 11

The table shows significant changes considering the time frames prior to and until 3–5 months (T1 to T2), as well as prior to and until 9–12 months after surgery (T1 to T3). Eighty-nine percent of patients were stable or significantly improved, while only 11% remained permanently impaired (T1 to T3).




tive speed and concentration, as well as working memory. These findings are in accordance with the results pub-lished by Tucha et al. relating to meningiomas at the con-vexity. Their results indicated that there are no differences in scores between pre- and postoperative assessments of attention and cognitive functions.28 Our results are further supported by Waagemans et al. who described the long-term impact of cognitive deficits and epilepsy on quality of life in patients with low-grade meningiomas.33 On 1-year follow-up assessments, patients who had undergone sur-gery did not differ from healthy controls in 7 of 8 SF-36 scales. Significant impairments were only detected in cog-nitive functions addressing executive functioning.33 This subqualification was also particularly affected in our pa-tients, indicating that executive functioning and cognitive speed are the skills most likely to be vulnerable to impair-ment by the tumor or the resection.

Although our patients showed transient, and in a minor-ity, also permanent deficits following surgery, anxiety and depression were not noted to be affected. In our study, only 6.5% and 3.5% of patients showed worsening of depres-sion and anxiety, respectively. This may be explained by the benign histological diagnosis, as there are contrasting reports regarding anxiety and depression in patients with primary brain tumors. In the cohort of D’Angelo et al., the number of patients suffering from anxiety and depression is higher, and depression increased significantly 1 and 3 months following surgery.8

As a result of improvement and implementation of al-ternative treatment options, radiotherapy plays an impor-tant role, both for primary and adjuvant treatment. Using FSRT, permanent cognitive dysfunction appears to occur at very low rates.26 In a further study on 507 patients with skull base meningiomas, high-precision photon radiation as either FSRT or IMRT was used as the first treatment modality in 53% and as an adjuvant treatment option fol-lowing surgery in 47%.6 Overall, local tumor control was achieved in 88% within a follow-up of 10 years. The self-reported quality of life of 340/507 completed question-naires was unchanged or had improved in 85.2%,6 but valid neuropsychological examinations are lacking. Compared with healthy controls, patients who underwent operations for skull base meningiomas showed lower neurocognitive functioning.32 However, patients who were treated with both surgery and radiotherapy had significantly lower health-related quality of life scores than patients with meningiomas who were treated with surgery only, who had health-related quality of life ratings comparable with healthy controls.32

ConclusionsThe results of our study demonstrate that surgical re-

moval of skull base meningiomas has positive effects on neuropsychological outcome in a considerable majority of patients. Long-term verbal memory, working memory, and executive functioning, however, were slightly affected within the first months following surgery and appeared to be likely the most vulnerable skills impaired by the tu-mor or the resection. Nevertheless, these data describe an overall recovery within the first year showing improved

or stable levels of short- and long-term verbal memory, vi-sual learning, quality of life, cognitive speed, and working memory.

These results are the first available data addressing these issues, and therefore, help us to better understand the problems faced by patients, particularly in relation to professional employment. As such, they will be of impor-tance in developing better strategies to help patients return to “normal life” and professional work following surgical removal of benign skull base meningiomas.

References 1. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull

A, Duez NJ, et al: The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instru-ment for use in international clinical trials in oncology. J Natl Cancer Inst 85:365–376, 1993

2. Arbuthnott K, Frank J: Trail Making Test, Part B as a mea-sure of executive control: validation using a set-switching paradigm. J Clin Exp Neuropsychol 22:518–528, 2000

3. Ausman JI: A revolution in skull base surgery: the quality of life matters! Surg Neurol 65:635–636, 2006

4. Black P, Kathiresan S, Chung W: Meningioma surgery in the elderly: a case-control study assessing morbidity and mortal-ity. Acta Neurochir (Wien) 140:1013–1017, 1998

5. Bowie CR, Harvey PD: Administration and interpretation of the Trail Making Test. Nat Protoc 1:2277–2281, 2006

6. Combs SE, Adeberg S, Dittmar JO, Welzel T, Rieken S, Habermehl D, et al: Skull base meningiomas: long-term results and patient self-reported outcome in 507 patients treated with fractionated stereotactic radiotherapy (FSRT) or intensity modulated radiotherapy (IMRT). Radiother Oncol 106:186–191, 2013

7. Curry WT, McDermott MW, Carter BS, Barker FG II: Cra-niotomy for meningioma in the United States between 1988 and 2000: decreasing rate of mortality and the effect of pro-vider caseload. J Neurosurg 102:977–986, 2005

8. D’Angelo C, Mirijello A, Leggio L, Ferrulli A, Carotenuto V, Icolaro N, et al: State and trait anxiety and depression in patients with primary brain tumors before and after surgery: 1-year longitudinal study. J Neurosurg 108:281–286, 2008

9. Dijkstra M, van Nieuwenhuizen D, Stalpers LJA, Wumkes M, Waagemans M, Vandertop WP, et al: Late neurocognitive sequelae in patients with WHO grade I meningioma. J Neu-rol Neurosurg Psychiatry 80:910–915, 2009

10. Fayers P, Bottomley A: Quality of life research within the EORTC-the EORTC QLQ-C30. Eur J Cancer 38 (Suppl 4):S125–S133, 2002

11. Fernández AL, Marcopulos BA: A comparison of normative data for the Trail Making Test from several countries: equiv-alence of norms and considerations for interpretation. Scand J Psychol 49:239–246, 2008

12. Helmstadeter C, Durwen H: The Verbal Learning and Reten-tion Test. A useful and differentiated tool in evaluating verbal memory performance. Schweiz Arch Neurol Psychiatry 141:21–30, 1990

13. Herman-Lingen C, Buss U, Snaith RP: HADS-D. Hospital Anxiety and Depression Scale, German Version. Berlin: Hans Huber, 2011

14. Khan F, Amatya B: Factors associated with long-term func-tional outcomes, psychological sequelae and quality of life in persons after primary brain tumour. J Neurooncol 111:355–366, 2013

15. Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifen-berger G, Burger PC, et al: The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 61:215–229, 2002




16. Krupp W, Klein C, Koschny R, Holland H, Seifert V, Meix-ensberger J: Assessment of neuropsychological parameters and quality of life to evaluate outcome in patients with surgi-cally treated supratentorial meningiomas. Neurosurgery 64:40–47, 2009

17. Levine NB, Demonte F: Functional outcome in the neuro-surgical patient and its impact on quality of life. Skull Base 20:19–22, 2010

18. Longstreth WT Jr, Dennis LK, McGuire VM, Drangsholt MT, Koepsell TD: Epidemiology of intracranial meningioma. Cancer 72:639–648, 1993

19. Lu L, Bigler ED: Performance on original and a Chinese version of Trail Making Test Part B: a normative bilingual sample. Appl Neuropsychol 7:243–246, 2000

20. McGrath J, Scheldt S, Welham J, Clair A: Performance on tests sensitive to impaired executive ability in schizophre-nia, mania and well controls: acute and subacute phases. Schizophr Res 26:127–137, 1997

21. Miao Y, Lu X, Qiu Y, Jiang J, Lin Y: A multivariate analysis of prognostic factors for health-related quality of life in pa-tients with surgically managed meningioma. J Clin Neurosci 17:446–449, 2010

22. Müller H, Hasse-Sander I, Horn R, Helmstaedter C, Elger CE: Rey Auditory-Verbal Learning Test: structure of a modi-fied German version. J Clin Psychol 53:663–671, 1997

23. Reitan RM, Tarshes EL: Differential effects of lateralized brain lesions on the trail making test. J Nerv Ment Dis 129:257–262, 1959

24. Sánchez-Cubillo I, Periáñez JA, Adrover-Roig D, Rodríguez-Sánchez JM, Ríos-Lago M, Tirapu J, et al: Construct validity of the Trail Making Test: role of task-switching, working memory, inhibition/interference control, and visuomotor abilities. J Int Neuropsychol Soc 15:438–450, 2009

25. Solana E, Poca MA, Sahuquillo J, Benejam B, Junqué C, Dronavalli M: Cognitive and motor improvement after re-testing in normal-pressure hydrocephalus: a real change or merely a learning effect? J Neurosurg 112:399–409, 2010

26. Steinvorth S, Welzel G, Fuss M, Debus J, Wildermuth S, Wannenmacher M, et al: Neuropsychological outcome after fractionated stereotactic radiotherapy (FSRT) for base of skull meningiomas: a prospective 1-year follow-up. Radio-ther Oncol 69:177–182, 2003

27. Tombaugh TN: Trail Making Test A and B: normative data stratified by age and education. Arch Clin Neuropsychol 19:203–214, 2004

28. Tucha O, Smely C, Preier M, Becker G, Paul GM, Lange KW: Preoperative and postoperative cognitive functioning in patients with frontal meningiomas. J Neurosurg 98:21–31, 2003

29. Tucha O, Smely C, Preier M, Lange KW: Cognitive deficits before treatment among patients with brain tumors. Neuro-surgery 47:324–334, 2000

30. van der Vossen S, Schepers VPM, Berkelbach van der Sp-renkel JW, Visser-Meily JMA, Post MWM: Cognitive and emotional problems in patients after cerebral meningioma surgery. J Rehabil Med 46:430–437, 2014

31. van Nieuwenhuizen D, Ambachtsheer N, Heimans JJ, Reijneveld JC, Peerdeman SM, Klein M: Neurocognitive functioning and health-related quality of life in patients with radiologically suspected meningiomas. J Neurooncol 113:433–440, 2013

32. van Nieuwenhuizen D, Klein M, Stalpers LJ, Leenstra S, Heimans JJ, Reijneveld JC: Differential effect of surgery and radiotherapy on neurocognitive functioning and health-related quality of life in WHO grade I meningioma patients. J Neurooncol 84:271–278, 2007

33. Waagemans ML, van Nieuwenhuizen D, Dijkstra M, Wumkes M, Dirven CMF, Leenstra S, et al: Long-term im-pact of cognitive deficits and epilepsy on quality of life in pa-tients with low-grade meningiomas. Neurosurgery 69:72–79, 2011

34. Wechsler D: WMS-R Wechsler Memory Scale—Revised. San Antonio: Harcourt Brace Jovanovich, 1987

35. Wechsler D, Tewes U: HAWIE-R: Hamburg-Wechsler In-telligenztest für Erwachsene—Revision. Bern: Hans Huber, 1991

36. World Health Organization: World Health Organization Constitution. Geneva: World Health Organization, 1948

37. Zigmond AS, Snaith RP: The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370, 1983

DisclosuresThe authors report no conflict of interest concerning the materi-als or methods used in this study or the findings specified in this paper.

Author ContributionsConception and design: Zweckberger, Vogt, Schick, Unterberg. Acquisition of data: Zweckberger, Halleck, Vogt, Giese. Analysis and interpretation of data: Zweckberger, Halleck, Vogt, Giese. Drafting the article: Zweckberger. Critically revising the article: Zweckberger, Giese, Schick, Unterberg. Reviewed submitted ver-sion of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Zweckberger. Statistical analysis: Zweckberger, Halleck, Vogt. Administrative/technical/material support: Giese, Schick, Unterberg. Study supervision: Zweckberger, Schick, Unterberg.

CorrespondenceKlaus Zweckberger, Department of Neurosurgery, University of Heidelberg, Im Neuenheimer Feld 400, Heidelberg 69120, Ger-many. email: [email protected].


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Prospective analysis of neuropsychological deficits