Abstract
BACKGROUND
Some patients experience long-term declines in quality of life following meningioma resection, but associated factors are not well understood.
OBJECTIVE
To investigate whether long-term declines in quality of life (specifically impaired adaptive functioning) after meningioma resection are associated with specific personality disturbances that often develop with lesions in ventromedial prefrontal cortex (vmPFC).
METHODS
We studied 38 patients who underwent resection of meningioma, 18 of whom had vmPFC lesions and 20 with lesions elsewhere (non-vmPFC). A total of 30 personality characteristics were rated by spouse or family, and a neuropsychologist blindly rated adaptive functioning an average of 3.8 yr postresection. Relevant personality disturbance was defined by a priori process: the presence of “conjoint personality disturbance” required specific disturbances in at least 2 of 4 types of disturbance: executive disorders, disturbed social behavior, emotional dysregulation, and hypoemotionality.
RESULTS
Fourteen patients had impaired adaptive functioning: 12 had vmPFC lesions and 2 had non-vmPFC lesions. Fourteen patients had conjoint personality disturbance, and 12 of them had impaired adaptive functioning. By contrast, among the 24 patients who did not have conjoint personality disturbance, only 2 had impaired adaptive functioning. Mediation analysis showed that the association between vmPFC lesions and impaired adaptive functioning was mediated by the negative impact of acquired personality disturbance on adaptive functioning.
CONCLUSION
Anterior skull base meningiomas plus resection surgery may result in specific personality disturbances that are highly associated with impaired adaptive functioning at long-term follow-up. These patients may benefit from early counseling regarding potential personality changes and their implications for adaptive functioning.
Keywords: Brain tumor, Frontal lobe, Iowa Scales of Personality Change, Personality change, Ventromedial prefrontal cortex
ABBREVIATIONS
- APD
acquired personality disturbance
- cjtAPD
conjoint APD
- ISPC
Iowa Scales of Personality Change
- QoL
quality of life
- SE
standard error
- vmPFC
ventromedial prefrontal cortex
Meningioma resection is highly successful for tumor removal with very low rates of morbidity and mortality,1,2 but following resection, some patients are unable to return to their premorbid level of functioning,3-7 an important aspect of outcome.8 Objective aspects of real life functioning (including occupational functioning, interpersonal relationships, social participation, and personal independence), referred to as “adaptive functioning,”9 are not well measured.6,10-12 Accordingly, little is known regarding factors associated with poor adaptive functioning postresection.
Two studies found that 19% to 35% of patients were unable to return to their premorbid work level following meningioma resection, but factors associated with poor outcomes were not reported.6,7 A third study showed considerable variability in quality of life (QoL), but the incidence of poor QoL outcomes was not reported.13 A recent study found that impaired adaptive functioning was highly associated with lesions of ventromedial prefrontal cortex (vmPFC), largely in patients with resection of anterior skull base meningiomas.14 The authors reported that impaired adaptive functioning was not associated with cognitive deficits, but patients with vmPFC lesions tended to develop acquired personality disturbances (APDs), and such disturbances appeared to be an important contributor to impaired adaptive functioning.
Associations between large anterior skull base meningiomas, vmPFC lesions, severe personality disturbances, and impaired adaptive functioning are also suggested by the landmark case of EVR.3 In middle age, following a life of exemplary functioning in all psychosocial spheres, EVR developed striking disturbances in emotionality, interpersonal sensitivity, impulse control, planning, judgment, and decision-making, resulting in estrangement from his wife and family and gross impairment in subsequent relationships, professional functioning, and management of financial affairs. Neuropsychological evaluation was eventually obtained, revealing that the profound changes in personality and social conduct were attributable to a large bilateral orbital and ventromedial lesion from an olfactory groove meningioma resected approximately 5 yr earlier. This pattern of APDs and impaired adaptive functioning is strongly reminiscent of Phineas Gage15 and other patients with focal vmPFC lesions from varied etiologies.16-21
A few case studies notwithstanding, the apparent link between vmPFC damage, personality disturbances, and adaptive functioning has not been investigated systematically or comprehensively. One limitation has been the lack of adequate methodologies for quantifying types of behavioral changes after brain damage.22 Instruments developed for use with psychiatric populations show poor sensitivity and limited validity when applied to premorbidly normal individuals with acquired personality changes.18,23,24 To address these issues, the Iowa Scales of Personality Change (ISPC)25,26 were developed, providing a validated instrument with demonstrated sensitivity and specificity to personality disturbances following brain damage.18,21,25
The objective of this study was to investigate whether the strong association between vmPFC lesions and impaired adaptive functioning found in a previous study14 is more directly attributable to personality disturbances caused by vmPFC damage in patients with meningiomas and resection surgery. The study features detailed assessment of personality changes. We hypothesized the following: (1) resected meningiomas resulting in vmPFC lesions are significantly associated with disturbances in specific personality characteristics from the domains of executive disorder, emotional dysregulation, disturbed social behavior, and hypoemotionality. (2) APDs from these domains are significantly associated with impaired adaptive functioning. (3) The association between impaired adaptive functioning and vmPFC lesions is mediated by those types of APDs. Additionally, to facilitate clinical application of study findings, we hypothesized that (4) a small set of specific APDs can accurately identify meningioma patients at risk for impaired adaptive functioning at long-term follow-up.
METHODS
Study Design, Setting, and Subjects
This was a retrospective cross-sectional study of patients who underwent resection for meningioma and were assessed between 2005 and 2016, coming from 2 sources at an academic medical center. A total of 36 came from a registry of research patients, and 2 were evaluated in the Neuropsychology Clinic.
All study data were collected at least 3 mo postoperatively (mean interval from resection to personality and outcome data collection was 3.8 ± 4.6 yr). The Institutional Review Board approved procedures; all patients provided informed consent. (See Text, Supplemental Digital Content for elaboration regarding the sample, neuroanatomical classification, measurement of personality disturbance, details regarding the primary variables—personality disturbance and adaptive functioning—and statistical analysis). This manuscript incorporates STROBE guidelines.
Neuroanatomical, Neurosurgical, and Neuropsychological Variables
Registry patients were extensively characterized neuroanatomically and neuropsychologically using rigorous laboratory protocols. Patients were categorized as vmPFC if lesions involved either or both gyrus rectus (9 males and 9 females) or non-vmPFC if lesions were elsewhere in the brain (10 males and 10 females). Lesion overlap maps for these groups are presented in Figure 1.
FIGURE 1.
Lesion overlap maps for vmPFC (upper row; n = 16) and non-vmPFC groups (lower row; n = 10). Lesion mapping necessary for inclusion in the overlap maps could not be obtained for 2 patients from the vmPFC group (with olfactory groove meningioma) and 10 patients from the non-vmPFC group (left parietooccipital, left parafalcine, and 2 right parafalcine meningiomas). Maximum overlap in the vmPFC group was 15/16; maximum overlap in the non-vmPFC group was 5/10.
Clinical/neurosurgical variables included chronicity (interval from initial symptom onset to personality assessment), tumor grade, surgical approach, degree of resection, lesion size, pre- and postoperative edema, and postoperative complication (infection or stroke), as presented in Table 1. Neuropsychological measures reported in this study are listed in Table 2.
TABLE 1.
Demographic Characteristics and Neurosurgical Variable by Study Group
| Characteristic | vmPFC (n = 18) | non-vmPFC (n = 20) | P value |
|---|---|---|---|
| Age (years) | 63.2 (13.7) | 55.7 (12.3) | .09 |
| Education (years) | 13.7 (2.3) | 14.1 (2.7) | .61 |
| Age at onset (years) | 59.7 (14.4) | 51.7 (11.7) | .07 |
| Interval (years)a | 3.5 (4.1) | 4.1 (5.0) | .69 |
| Tumor grade (% of study group) | .41 | ||
| Grade I | 92.9% | 100% | |
| Grade II | 7.1% | 0% | |
| Surgical approach (%) | .17d | ||
| Frontal, bifrontal | 55.6% | 10.0% | .004e |
| Frontal, left | 11.1% | 10.0% | |
| Frontal, right | 16.7% | 30.0% | |
| Frontoparietal, left | 0.0% | 10.0% | |
| Pterional, left | 11.1% | 5.0% | |
| Pterional, right | 0.0% | 5.0% | |
| Frontotemporal, left | 5.6% | 0.0% | |
| Frontotemporal, right | 0.0% | 5.0% | |
| Posteriorb | 0.0% | 25.0% | |
| Gross total resections (%) | 100% | 100% | |
| Lesion size (mm) | 40.7 (17.9) | 37.4 (17.9) | .59 |
| Peritumor edema, preop (%) | 73.3% | 65% | .72 |
| Peritumor edema, postop (%) | 5.0% | 18.8% | .31 |
| Postoperative complicationsc | 0% | 0% | - |
vmPFC = lesions in ventromedial prefrontal cortex. Non-vmPFC = lesion outside of ventromedial prefrontal cortex.
Values presented for continuous variables are the mean (and standard deviation), and for categorical variables are the percent within each study group.
aInterval refers to the length of time from the first evidence of symptoms to follow-up.
bThese included one resection each: left frontotemporal, right frontotemporal, left temporal, right temporoparietal, left parietal, left parietooccipital, left occipital.
cIncludes stroke and infection.
dOverall, surgical approach was not significantly associated with vmPFC status, as evaluated by chi square[12] = 14.7, P = .26.
eThe association of a bifrontal approach, specifically, to vmPFC status was evaluated by Fisher's exact test (chi square[1] = 7.09).
TABLE 2.
Basic Neuropsychological Characteristics by Study Group
| Variable | vmPFC Mean score (SD) |
non-vmPFC Mean score (SD) |
P value |
|---|---|---|---|
| WAIS VIQ/VCI | 104.7 (15.0) | 100.1 (13.2) | .39 |
| WAIS PIQ/PRI | 105.9 (16.7) | 102.9 (12.3) | .60 |
| WAIS PSI | 105.5 (13.1) | 100.5 (21.3) | .49 |
| WAIS WMI | 103.6 (13.0) | 97.4 (12.9) | .22 |
| AVLT Trial 5 | 10.3 (3.8) | 11.6 (2.7) | .27 |
| AVLT delayed recall | 8.1 (3.7) | 9.3 (4.0) | .38 |
| Trailmaking Test-A (seconds) | 37.1 (14.1) | 36.2 (13.2) | .86 |
| Trailmaking Test-A (errors) | 0.0 (0.0) | 0.0 (0.0) | – |
| Trailmaking Test-B (seconds) | 95.5 (44.3) | 94.2 (60.7) | .94 |
| Trailmaking Test-B (errors) | 0.6 (1.1) | 0.2 (0.4) | .27 |
| Beck Depression Inventory-II | 5.4 (4.0) | 10.9 (6.7) | .008 |
vmPFC = lesions in ventromedial prefrontal cortex. Non-vmPFC = lesion outside of ventromedial prefrontal cortex. WAIS = Wechsler Adult Intelligence Scale (3rd or 4th edition). VIQ/VCI = Verbal Intelligence Quotient or Verbal Comprehension Index. PIQ/PRI = Performance Intelligence Quotient or Perceptual Reasoning Index. PSI = Processing Speed Index; WMI = Working Memory Index; AVLT = Auditory Verbal Learning Test.
Personality
The ISPC25,26 assesses 30 personality characteristics, with ratings made by family for both current functioning and characteristic premorbid functioning (prior to onset of any symptoms or behavioral changes reasonably associated with the meningioma). Ratings comprise a 7-point scale; higher ratings reflect increasing disturbance. (Four control scales are not included in analyses.)
Conjoint APD
For each characteristic, an “acquired personality disturbance” is defined by (1) at least mild disturbance (current rating >4) and (2) significant increase (change >2). The large number of personality variables (26) and their ordinal scaling present challenges to statistical evaluation. To address this, personality data were reduced to the presence/absence of a variable—labeled “conjoint APD” (cjtAPD)—to reflect disturbance of a nature expected to impair adaptive functioning. In the first step, the one APD most highly associated with adaptive functioning from each of 4 dimensions of disturbance16—executive disorder, disturbed social behavior, emotional dysregulation, and hypoemotionality—was selected. Second, the presence of cjtAPD was defined by the presence of 2 or more APDs from among the 4 specific disturbances so selected (additional details are in Text, Supplemental Digital Content).
Adaptive Functioning
Adaptive functioning refers to functioning in major life roles9 (independence, occupational functioning, interpersonal relationships and social participation, and emotional equilibrium6,9-12,14), but not incorporating subjective sense of satisfaction. Ratings were based on extensive interviews of patients and family and review of clinical notes by a neuropsychologist blind to study group: 0 = no compromise, 1 = mild compromise, 2 = moderate impairment, and 3 = severe impairment. These ratings were dichotomized to indicate either (1) essentially adequate adaptive functioning (ratings of 0-1) or (2) impaired adaptive functioning (ratings of 2-3).
Statistical Analysis
Analyses were performed with SPSS for Windows 23.0 (IBM Corporation).27 The 2 study groups were compared on demographic, clinical, and neurosurgical variables and adaptive functioning with t-tests for interval scale variables, Mann-Whitney U tests for ordinal variables, and chi-square or Fisher's exact test for categorical variables as appropriate. Alpha was set at .05 except when stated otherwise. To test the first hypothesis, differences between vmPFC and non-vmPFC in the rates of the 19 APDs from the dimensions of executive disorders, emotional reactivity, disturbed social behavior, and hypoemotionality were evaluated with Fisher's exact tests with a more stringent alpha level of .01 because of multiple tests. One-tailed tests were employed for hypothesized differences. The potential influence of type I error was assessed by examining the extent to which the obtained pattern of results fit with the predicted pattern. To test the second hypothesis, we evaluated differences in rates of APDs between the 2 outcome groups (impaired vs essentially adequate adaptive functioning).
Mediation analysis with a series of Firth logistic regressions28-31 was employed to evaluate the third hypothesis: that APD mediates the effect of vmPFC damage on adaptive function. Because the variables’ different scales affect raw beta weights, the betas are not directly comparable as indices of relationship strength. Therefore, coefficients were standardized to create comparable beta weights32,33 and to calculate the percentage of mediation effect,34 evaluated by the Sobel test.35
To test the hypothesis that a small set of specific APDs can accurately identify individual patients at risk for impaired adaptive functioning, we report the sensitivity, specificity, positive predictive power, negative predictive power, and overall predictive accuracy of cjtAPD status. In this paper, “predictive accuracy” refers to status on the independent variable predicting status on the dependent variable at the time of data collection.
RESULTS
Demographic and Clinical Characteristics
There were no significant differences between vmPFC and non-vmPFC on any demographic or clinical or neurosurgical variables other than the natural association between vmPFC lesions and bifrontal approach (Table 1). They did not differ on basic cognitive variables (Table 2). vmPFC had significantly lower depression (minimal symptoms) than non-vmPFC, t(36) = 2.84, P = .008.
Personality Disturbances
Rates of APD were significantly higher among vmPFC (Table 3) for poor judgment (F[1] = 11.77, P = .001), perseverative behavior (F[1] = 9.81, P = .002), lack of persistence (F[1] = 8.16, P = .006), indecisiveness (F[1] = 6.92, P = .01), irritability (F[1] = 11.77, P = .001), inflexibility (F[1] = 19.49, P < .001), lack of insight (F[1] = 11.00, P = .001), apathy (F[1] = 8.16, P = .006), and blunted affect (F[1] = 7.92, P = .007).
TABLE 3.
Level of Personality Disturbances, Mean Change, and Rates of Acquired Personality Disturbances
| Personality functioning Mean rating (SD) | Change Mean score (SD) | Rate of acquired personality disturbance | |||||
|---|---|---|---|---|---|---|---|
| Personality characteristic | vmPFC | Non-vmPFC | vmPFC | Non-vmPFC | vmPFC | Non-vmPFC | P value |
| Poor judgment | 4.3 (2.1) | 3.0 (1.4) | 1.9 (2.1) | 0.3 (0.9) | 55.6% | 5.0% | .001 |
| Lack of planning | 3.6 (2.2) | 2.6 (1.3) | 1.8 (1.9) | 0.3 (1.1) | 38.9% | 5.0% | .02 |
| Perseverative behavior | 4.2 (1.6) | 3.2 (1.1) | 1.4 (1.5) | 0.5 (1.4) | 50.0% | 5.0% | .002 |
| Lack of initiative | 4.3 (2.1) | 3.0 (1.4) | 2.1 (2.6) | 1.0 (1.4) | 61.1% | 20.0% | .02 |
| Lack of persistence | 3.6 (2.0) | 2.5 (1.2) | 1.2 (1.6) | 0.3 (0.9) | 44.4% | 5.0% | .006 |
| Indecisiveness | 4.4 (1.9) | 3.3 (1.6) | 1.7 (1.6) | 0.9 (1.6) | 55.6% | 15.0% | .01 |
| Impulsivity | 3.4 (1.7) | 2.8 (1.6) | 1.1 (1.6) | 0.3 (0.7) | 27.8% | 5.0% | .07 |
| Insensitivity | 3.7 (2.0) | 3.5 (1.5) | 1.3 (1.7) | 0.3 (2.1) | 44.4% | 15.0% | .05 |
| Social inappropriateness | 3.6 (2.0) | 2.9 (1.0) | 2.1 (1.9) | 0.3 (1.0) | 44.4% | 10.0% | .02 |
| Inappropriate affect | 3.4 (1.5) | 2.8 (0.9) | 1.2 (1.4) | 0.3 (0.6) | 16.7% | 5.0% | .26 |
| Aggressive behavior | 3.0 (1.0) | 2.2 (1.0) | 0.7 (1.3) | –0.1 (1.2) | 11.1% | 0.0% | .22 |
| Impatience | 4.3 (1.8) | 3.8 (1.5) | 1.2 (1.5) | 0.5 (1.9) | 44.4% | 10.0% | .02 |
| Irritability | 4.4 (1.7) | 3.0 (1.3) | 1.5 (2.1) | –0.1(1.5) | 55.6% | 5.0% | .001 |
| Lability | 4.7 (1.5) | 3.6 (1.3) | 1.7 (1.7) | 0.5 (1.7) | 44.4% | 20.0% | .10 |
| Inflexibility | 5.2 (1.6) | 3.8 (1.2) | 1.8 (2.3) | –0.1 (1.1) | 66.7% | 0.0% | <.001 |
| Lack of insight | 4.2 (2.0) | 2.5 (1.1) | 4.2 (2.0) | 2.5 (1.1) | 61.1% | 10.0% | .001 |
| Apathy | 4.2 (1.6) | 3.2 (1.3) | 1.6 (1.8) | 0.2 (0.9) | 44.4% | 5.0% | .006 |
| Blunted affect | 3.4 (1.9) | 3.1 (1.1) | 0.8 (2.0) | –0.1 (1.1) | 33.3% | 0.0% | .007 |
| Social withdrawal | 3.3 (1.7) | 3.3 (1.7) | 0.8 (1.5) | 0.4 (1.3) | 22.2% | 20.0% | .59 |
| Depression | 4.2 (1.4) | 3.4 (1.6) | 1.5 (2.0) | 0.5 (1.5) | 38.9% | 15.0% | .14 |
| Anxiety | 3.8 (1.4) | 3.5 (2.0) | 0.9 (1.2) | 0.7 (1.3) | 27.8% | 20.0% | .71 |
| Easily overwhelmed | 4.2 (1.4) | 3.4 (1.8) | 1.6 (1.6) | 0.8 (1.4) | 44.4% | 20.0% | .16 |
| Dependency | 2.5 (1.4) | 3.1 (1.3) | 0.3 (1.5) | 0.7 (1.2) | 16.7% | 10.0% | .65 |
| Lack of stamina | 4.5 (1.7) | 3.9 (1.2) | 1.7 (2.0) | 0.9 (1.5) | 44.4% | 20.0% | .16 |
| Obsessiveness | 4.1 (1.4) | 3.9 (1.5) | 0.5 (1.7) | 0.2 (1.4) | 27.8% | 5.0% | .08 |
| Suspiciousness | 3.7 (1.5) | 2.9 (0.9) | 0.7 (1.3) | –0.1 (0.6) | 27.8% | 0.0% | .02 |
vmPFC = lesions in ventromedial prefrontal cortex. Non-vmPFC = lesion outside of ventromedial prefrontal cortex.
Bolded font indicates personality characteristics expected to differ between groups because they comprise the 4 dimensions of acquired disturbance associated with vmPFC lesions (executive disorder, disturbed social behavior, emotional dysregulation, and hypoemotionality).
Impaired Adaptive Functioning
Adaptive functioning (Table 4) was significantly worse among vmPFC than non-vmPFC on the original 4-point scale (chi-square[3] = 13.4, P = .002). On the dichotomized outcome measure, moderate to severe impairment of adaptive functioning was significantly more likely among vmPFC (66.7%) than among non-vmPFC (10%) (chi-square[1] = 13.1, P < .001 by Fisher exact test). No demographic, cognitive, or neurosurgical variable was associated with adaptive function ratings, with the exception of bifrontal approach (chi-square[1] = 7.09).
TABLE 4.
Adaptive Functioning by Study Group
| vmPFC Number (%) | Non-vmPFC Number (%) | P | |
|---|---|---|---|
| Adaptive functioning (4-point rating) | .002a | ||
| Normal | 4 (22.2%) | 11 (55.0%) | |
| Mild compromise | 2 (11.1%) | 7 (35.0%) | |
| Moderate impairment | 9 (50.0%) | 2 (10.0%) | |
| Severe impairment | 3 (16.7%) | 0 (0.0%) | |
| Adaptive functioning, dichotomized | .001b | ||
| Normal or mild compromise | 6 (33.3%) | 18 (90.0%) | |
| Moderate to severe impairment | 12 (66.7%) | 2 (10.0%) | |
| Total | 18 (100%) | 20 (100%) |
vmPFC = lesions in ventromedial prefrontal cortex. Non-vmPFC = lesion outside of ventromedial prefrontal cortex.
aThe significance of the association between vmPFC status and the 4-point rating scale of adaptive functioning was evaluated by chi square[3] = 13.4, P = .002.
bThe significance of the association between vmPFC status and the dichotomized adaptive functioning outcome measure was by Fisher's exact test (chi square[1] = 13.1, P > .001).
Personality Disturbance and Adaptive Functioning
The 4 specific disturbances with the strongest association with impaired adaptive functioning from the 4 dimensions of disturbance (Table 5) were indecisiveness (Mann-Whitney U = 41.0, P < .001), social inappropriateness (U = 63.5, P = .001), inflexibility (U = 63.5, P = .001), and apathy (U = 50.0, P < .001). These disturbances formed the basis of cjtAPD.
TABLE 5.
Mean Ratings of Specific Personality Disturbances in Groups With and Without Impaired Adaptive Functioning
| Adaptive functioning | |||||
|---|---|---|---|---|---|
| Personality Dimension Personality characteristic | Nonimpaired | Impaired | Mann-Whitney U statistic | P value | |
| Executive disorder | |||||
| Poor judgment | 2.8 (1.6) | 4.9 (1.8) | 68.5 | .001 | |
| Lack of planning | 2.6 (1.3) | 3.9 (2.2) | 112.0 | .05 | |
| Perseverative behavior | 3.1 (1.1) | 4.7 (1.3) | 56.0 | <.001 | |
| Lack of initiative | 2.9 (1.6) | 4.9 (1.7) | 65.5 | <.001 | |
| Lack of persistence | 2.4 (1.3) | 4.1 (1.9) | 80.0 | .007 | |
| Indecisiveness | 3.0 (1.3) | 5.4 (1.6) | 41.0 | <.001 | |
| Impulsivity | 2.7 (1.5) | 3.8 (1.8) | 105.5 | .03 | |
| Disturbed social behavior | |||||
| Insensitivity | 3.3 (1.7) | 4.2 (1.6) | 110.5 | .05 | |
| Insensitivity | 3.3 (1.7) | 4.2 (1.6) | 110.5 | .05 | |
| Social inappropriateness | 2.7 (1.4) | 4.3 (1.5) | 63.5 | .001 | |
| Inappropriate affect | 2.8 (1.1) | 3.5 (1.4) | 115.0 | .06 | |
| Aggressive behavior | 2.2 (1.0) | 3.3 (0.9) | 76.0 | .003 | |
| Emotional dysregulation | |||||
| Impatience | 3.7 (1.4) | 4.5 (2.0) | 121.0 | .08 | |
| Irritability | 3.1 (1.4) | 4.6 (1.6) | 80.0 | .004 | |
| Lability | 3.7 (1.4) | 4.9 (1.3) | 89.0 | .008 | |
| Inflexibility | 3.8 (1.3) | 5.4 (1.5) | 60.5 | .001 | |
| Lack of insight | 2.7 (1.4) | 4.4 (1.8) | 67.0 | .001 | |
| Hypoemotionality | |||||
| Apathy | 3.0 (1.1) | 4.9 (1.4) | 50.0 | <.001 | |
| Blunted affect | 3.0 (1.3) | 3.6 (1.9) | 140.5 | .21 | |
| Social withdrawal | 2.9 (1.2) | 3.9 (2.1) | 118.0 | .07 | |
| Distress | |||||
| Depression | 3.0 (1.3) | 4.9 (1.2) | 45.0 | .001 | |
| Anxiety | 3.3 (1.8) | 4.3 (1.6) | 107.0 | .07 | |
| Easily overwhelmed | 3.0 (1.6) | 5.0 (0.9) | 50.0 | <.001 | |
| Dependency | 2.8 (1.3) | 2.8 (1.5) | 165.0 | .47 | |
| Freestanding scales | |||||
| Lack of stamina | 3.8 (1.3) | 4.8 (1.6) | 93.5 | .02 | |
| Obsessiveness | 3.9 (1.3) | 4.1 (1.6) | 156.5 | .45 | |
| Suspiciousness | 3.3 (0.9) | 3.3 (1.7) | 161.0 | .43 | |
Bolded font indicates personality characteristics with largest differences between adaptive functioning groups (indicated by lowest Mann-Whitney U statistic).
Mediation Analysis
As presented in Figure 2, vmPFC status was associated with impaired adaptive functioning, (β = 2.60; standard error (SE) = 0.85; P < .001), and vmPFC status was associated with cjtAPD (β = 2.94; SE = 1.00; P < .001). Controlling for vmPFC status, cjtAPD status was associated with impaired adaptive functioning (β = 3.14; SE = 1.14; P = .001). After controlling for the mediator variable (cjtAPD), vmPFC status was no longer a significant predictor of adaptive functioning (β = 1.37; SE = 1.06; P = .18). Mediation analysis with “comparable betas” (cβ) indicated that 48% of the relationship between vmPFC status and adaptive functioning was attributable to the effect of cjtAPD on adaptive functioning, a significant mediating effect (Sobel test: z = 2.01, P = .04).
FIGURE 2.
Mediation analysis of a causal model in which damage to ventromedial prefrontal cortex causes impaired adaptive functioning indirectly by causing acquired personality disturbances, which are the primary cause of the impairment. Statistics presented are “comparable betas” calculated from Firth logistic regressions for comparable coefficients, and standard errors. A, The total effect of ventromedial damage on adaptive functioning. B, The proportion of the effect from ventromedial damage that is mediated by acquired personality disturbance vs the residual direct effect of ventromedial prefrontal damage on adaptive functioning.
Predictive Accuracy of cjtAPD
Of the 14 patients with impaired adaptive functioning (Table 6), 12 were cjtAPD+ (sensitivity, .86). Of 24 patients with normal or mildly compromised adaptive functioning, only 2 were cjtAPD+ (specificity, .92). Of 14 cjtAPD+ patients, 12 had impaired adaptive functioning (positive predictive power, .86). Of 24 cjtAPD– patients, 22 had normal or mildly compromised adaptive functioning (negative predictive power, .92).
TABLE 6.
Associations of Selected Acquired Personality Disturbances and Conjoint Acquired Personality Disturbances With Impaired Adaptive Functioning
| Selected APDs | |||||
|---|---|---|---|---|---|
| Indecisive | Social inappropriateness | Inflexibility | Apathy | Conjoint APDa | |
| True positives (APD+, IAF+) | 10 | 8 | 10 | 7 | 12 |
| False positives (APD+, IAF–) | 3 | 2 | 2 | 2 | 2 |
| True negatives (APD–, IAF–) | 21 | 22 | 22 | 22 | 22 |
| False negatives (APD–, IAF+) | 4 | 6 | 4 | 7 | 2 |
| Sensitivity | .71 | .57 | .71 | .50 | .86 |
| Specificity | .88 | .92 | .92 | .92 | .92 |
| Positive predictive power | .77 | .80 | .83 | .78 | .86 |
| Negative predictive power | .84 | .79 | .85 | .79 | .92 |
| Overall predictive accuracy | .82 | .79 | .84 | .76 | .89 |
APD = acquired personality disturbance. IAF = impaired adaptive functioning.
acjtAPD was defined by the presence of 2 or more APDs from among the 4 specific disturbances representing 4 dimensions of acquired personality disturbance: executive disorder, disturbed social behavior, emotional dysregulation, and hypoemotionality.
DISCUSSION
Some patients have declines in QoL following meningioma resection.5,6,14,36 Factors associated with poor long-term adaptive functioning—objective aspects of QoL—have received little study, but such impairments have been most clearly associated with vmPFC lesions.14 The present investigation examines the hypothesis that impairment in adaptive functioning is primarily attributable to the development of personality disturbances associated with anterior skull base meningiomas with resection. We emphasize that, as all patients were assessed after resection, this study cannot disentangle effects of the meningioma itself and those from resection surgery. In fact, the approach to olfactory groove meningiomas can require significant retraction on the frontal lobes, which may contribute to a vmPFC lesion. With this in mind, we emphasize that we have investigated the effects of lesions resulting from the combined effects of tumor plus surgery and cannot speak to the relative contributions of the meningioma vs surgical variables.
Key Results
Detailed personality ratings indicate that premorbidly, patients’ personalities were normal, but after development of the meningioma and resection, patients with vmPFC lesions developed widespread personality disturbances of the types expected to be affected. A total of 16 of 19 characteristics from the domains hypothesized to become disturbed with vmPFC damage showed greater disturbance than among non-vmFC at levels below the .10 P level. Though widespread, these personality changes were not nonspecific as vmPFC lesions were not associated with significantly greater disturbance in any of the personality characteristics not hypothesized to differ between groups. Patients with meningiomas elsewhere in the brain had very low rates of APDs, largely in the 0% to 10% range. The specific set of APDs found in this study is highly similar to the pattern of disturbances described in other patients with focal ventromedial prefrontal lesions from varied etiologies.3-7,16-21
Study findings support the proposition that APDs associated with vmPFC lesions are the “missing link” in explaining impaired adaptive functioning in some patients following resection surgery. Mediation analysis demonstrated that impaired adaptive functioning among patients with vmPFC lesions is primarily because of development of the types of APDs caused by vmPFC damage. This is consistent with past reports of impaired adaptive functioning in vmPFC patients with executive disorders, disturbed social behavior, emotional dysregulation, and hypoemotionality.3,37,38 Impairment in adaptive functioning seen in this study was not associated with neurosurgical variables (other than bifrontal approaches for resection of anterior skull base meningiomas—associated with vmPFC lesions), demographic characteristics, basic cognitive abilities, or mood.
Our findings are broadly consistent with the literature. In contrast to the robust association between poor adaptive functioning outcomes and personality disturbances, impairments in adaptive functioning after meningioma resection have not shown consistent associations with other factors. Several studies have indicated that some limited number of meningioma patients undergoing resection have been unable to return to their premorbid level of professional or daily functioning up to 19%.5,6 Personality changes were not systematically assessed in any of these studies, but several studies hint at a possible contribution from personality disturbances to impaired adaptive functioning. One study found that 19% of their patients had reduced ability to work, and 20% reported personality changes, but a possible association between the 2 was not examined.5 Another study also found that 19% were unable to return to their premorbid level of professional or daily functioning, and “a combination of comorbid conditions and postoperative deterioration of somatic and cognitive performance caused working disability” for all but one.6 A third study reported that most patients were able to return to their previous occupation, but that a “psycho-organic” syndrome was seen in all 18 patients.36 A fourth study found that a higher rate of impaired adaptive functioning postresection among patients with vmPFC lesions was not associated with deficits in basic cognitive abilities, but the investigators observed that behavioral disturbances appeared to play a key role in poor work outcomes.14 In the most recent study, a minority of patients with skull base meningiomas reported declines in QoL at 14-mo follow-up, but personality changes were not assessed.13
Counterintuitively, patients with vmPFC lesions in this study reported a minimal level of depressive symptomatology, significantly less than meningioma patients with lesions elsewhere. Rather than superior mental health, this likely reflects dampened emotional functioning and apathy in patients with focal vmPFC lesions, and reduced insight into their neurobehavioral changes.16,18,19,22,39
Limitations
Major limitations of this study include the small sample size and a nonconsecutive series of patients who underwent neuropsychological/personality assessment. These weaknesses may reduce the generalizability of findings. Patients referred for neuropsychological evaluation typically have more noticeable cognitive deficits or behavioral changes, so patients in this study may have more pronounced deficits than the typical patient. That possibility may add weight to the finding that impaired adaptive functioning was not associated with deficits in basic cognitive domains. However, despite the small sample size and limited statistical power, the hypothesized pattern of results was observed.
Another limitation is the absence of preoperative measurements of lesion size, precluding assessment of the effects of the meningioma itself vs those from resection surgery. Accordingly, our analyses investigate the effects of the lesion resulting from the combined effects of tumor plus surgery. Additionally, we cannot rule out the possibility that an unexamined factor associated with removal of prefrontal meningiomas, rather than the lesion location per se, may be the mechanism for impaired adaptive functioning. However, there are reasons that are unlikely: the removal of the lesion via craniotomy was rarely associated with impaired QoL with non-vmPFC lesions. It is notable that, prior to meningioma resection of anterior skull base meningiomas, patients show dysfunctional personality changes of the sort associated with impaired adaptive functioning,3,4,40-42 and the same types of personality disturbances are also seen in patients with vmPFC damage from other (nonsurgical) sources.16-21 Tumors that underwent bifrontal approaches had the most significant deficits, raising a question whether some impairment may be preventable through selection of approaches that avoid bifrontal manipulation. In future investigations, adding preoperative measurements of neuropsychological function will allow the impact of the approach to be more clearly understood.
A feature of this study that might be considered a limitation is the somewhat convoluted definition of cjtAPD. However, a primary goal of this study was to capture the relevant aspects of APDs in a way that could be easily applied clinically. Accordingly, the a priori plan called for defining personality disturbance with (1) straightforward determination of whether a specific disturbance was present or absent, and (3) reference to a limited number of specific disturbances. The a priori requirement that APDs from at least 2 different dimensions of personality disturbance be present (in order to enhance prognostic relevance to adaptive functioning) was found to operate as intended: The high levels of sensitivity, specificity, positive predictive power, and negative predictive power indicate that cjtADP, as defined, effectively captured personality changes that are clearly related to long-term impairment in adaptive functioning. The degree to which our setting and our patients are representative of other settings is not known and because of capitalization on chance, the “predictive accuracy” found in this study (0.89) likely over-represents the level of accuracy of cjtAPD for other meningioma samples. However, this study's basic premise that a primary factor in development of impaired adaptive functioning is development of certain types of APDs was strongly supported. Cross-validation of findings will be important.
CONCLUSION
Patients with vmPFC lesions resulting from anterior skull base meningiomas and resection surgery may develop personality disturbances. Specific personality disturbances associated with vmPFC lesions are robustly related to development of impaired adaptive functioning, such as disruption of intimate relationships, inability to maintain employment, and financial deterioration. Heretofore, the risk for poor long-term psychosocial outcomes in patients with meningioma may have been difficult to recognize prospectively. Present findings indicate that a significant risk can be identified by the presence of 2 or more relevant personality disturbances (indecisiveness, social inappropriateness, inflexibility, and apathy). Early detection and resection of anterior skull base meningiomas impinging on vmPFC may reduce the incidence of these undesirable outcomes, though this requires further investigation. Presurgical counseling to these patients and family regarding potential behavioral changes may be beneficial. Neuropsychological assessment with careful attention to personality should be considered, particularly for patients with anterior skull base meningiomas and, when appropriate, neuropsychological rehabilitation may be initiated to prevent or minimize psychosocial morbidity.43
Disclosures
This research was supported in part by a McDonnell Foundation Collaborative Award 220020387, National Institute of Mental Health (1 P50 MH094258), and the Kiwanis Foundation. The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Dr Abel was supported by a National Institutes of Health (NIH F32-NS087664). Dr Okerstrom-Jezewski was supported by the McElroy Trust and the University of Iowa Graduate College.
Supplementary Material
Contributor Information
Joseph Barrash, Department of Neurology, University of Iowa, Iowa City, Iowa; Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa.
Taylor J Abel, Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
Katrina L Okerstrom-Jezewski, Department of Neurology, University of Iowa, Iowa City, Iowa.
Mario Zanaty, Department of Neurosurgery, University of Iowa, Iowa City, Iowa.
Joel E Bruss, Department of Neurology, University of Iowa, Iowa City, Iowa.
Kenneth Manzel, Department of Neurology, University of Iowa, Iowa City, Iowa.
Matthew Howard, III, Department of Neurosurgery, University of Iowa, Iowa City, Iowa.
Daniel Tranel, Department of Neurology, University of Iowa, Iowa City, Iowa; Department of Psychological and Brain Sciences, University of Iowa, Iowa City, Iowa.
Supplemental Digital Content. Text. The Supplemental Digital Content provides details and rationales for study methods.
COMMENT
This paper presents neuropsychological outcomes impacting QoL following resection of meningiomas, comparing vmPFC lesions and non-vmPFC. This study represents a critical aspect of the evaluation of patients following brain surgery and one that should be a key future outcome measure. This study sets the stage for accurate assessment of frontal lobe function, often ignored to the detriment of patients.
Unfortunately, since changes were measured after resection it is impossible to know if these are lesion- or approach-based morbidities. However, there appear to be significant differences in approaches selected (as common sense would indicate). The fact that tumors that underwent bifrontal approaches had the most significant deficits is worthy of further study to understand how much of this is preventable through selection of approaches that avoid bifrontal manipulation. Indeed, tumor factors such as degree of resection, preop and postop tumor size, postoperative edema, and complications did not seem to have the same dramatic impact on neuropsychological function.
In the future, by adding preoperative measurements of neurocognitive function, the impact of the approach can be more clearly understood. The lack of these is a major limitation of the study, but this paper has great value in introducing the concept of neuropsychological testing as an outcome measure for anterior fossa meningioma resection. This should become the standard of care for evaluating these tumors and their outcomes.
Felicia Goldstein
Atlanta, Georgia
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