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Clinical Research: Epidemiology Meets Neuro-Ophthalmology

Long-Term Patient-Reported Outcomes of Visual Field Defects and Compensatory Mechanisms in Patients After Cerebral Hemispherectomy

Meer, Elana A. BA; Chen, Monica F. BA; Jones, Monika JD; Mathern, Gary W. MD; Pineles, Stacy L. MD, MS

Editor(s): Moss, Heather E. MD, PhD; Pineles, Stacy L. MD

Author Information
Journal of Neuro-Ophthalmology: June 2021 - Volume 41 - Issue 2 - p 147-153
doi: 10.1097/WNO.0000000000000998

Abstract

INTRODUCTION

For over 50 years, hemispherectomy procedures have been performed to treat intractable epilepsy due to etiologies such as perinatal stroke, malformations of cortical development, Rasmussen encephalitis, and Sturge–Weber syndrome (1). An umbrella term for any of the multiple neurosurgical procedures in which a cerebral hemisphere is removed, disconnected, or disabled, hemispherectomy has demonstrated success in cases of seizure disorders in which the source of epilepsy is localized to one cerebral hemisphere. However, these procedures often result in substantial visual field defects, such as homonymous hemianopia, in which the contralateral visual field is lost on the same side of both eyes. In a recent systemic review, it was found that 5 years after hemispherectomy surgery, 71% of children were seizure-free (2); however, the optimal timing of surgery, depending on age of presentation and effect of underlying pathology, is still very unclear. Furthermore, although the immature brain may be expected to compensate for impaired function if surgery is performed early (3), there has been little definitive research to determine the long-term functional effects of resulting visual field defects (4).

Previous studies have explored the visual field defect and compensatory mechanisms over time; however, the functional visual outcome after cerebral hemispherectomy is still unclear (5). Unfortunately, such studies are limited by many factors, including long-term follow-up on visual function. For example, Devlin et al (6) demonstrated that, as expected, visual fields were either unchanged if already impaired or worse following surgery; however, postoperative follow-up was limited. Koenraads et al (7) sought to determine the visual outcome and prevalence of compensatory mechanisms in children after hemispherectomy by retrospectively reviewing postoperative ophthalmic examination of visual fixation, visual acuity, visual fields, optic discs, head posturing, ocular alignment, and cognitive development. All children assessed with visual field assessment had a homonymous hemianopia. Some children developed a contralateral exotropia, which the authors opined may be a compensatory mechanism that expanded the visual field, but did not address whether the exotropia was instead a result of oculomotor impairments from the surgery. In addition, the cohort median follow-up time was 2.3 years, not nearly long enough time to fully evaluate the childrens' development, visual field defects, or outcomes after hemispherectomy. Furthermore, visual field defects specifically were not assessed over time in the context of other demographic factors.

Hemispherectomy procedures may be the only option to attempt to allow children with intractable epilepsy to grow and develop to lead relatively stable lives (5). However, without clear research demonstrating how visual fixation, acuity, and fields may be affected by the surgery over time, the possible functional strategies children may develop to compensate for the homonymous hemianopsia, and the potential factors that may ameliorate the progression, it is challenging to holistically counsel parents of children who will undergo hemispherectomy. Furthermore, given the dearth of longitudinal studies, it is difficult to provide parents with timelines of compensatory improvement, or characteristics of improvement along the course of the child's development.

The aim of this study was to examine how the impact of postoperative visual field defects subjectively changed over time with use of compensatory mechanisms, and how contributing factors such as age of surgery, gender, etiology of epilepsy, age of onset of epilepsy and duration, and improvement of epilepsy/outcome of surgery may affect this. This study uses subjective measures of visual field defect improvement based on parental experience and observation, and builds on previous studies by inquiring about compensatory mechanisms that optimize visual field function.

METHODS

The study protocol was certified as exempt by the Institutional Review Board of the University of California of Los Angeles (IRB 17-000725-AM-00002). The Brain Recovery Project: Childhood Epilepsy Surgery Foundation, a U.S.-based nonprofit organization which works with families of children impacted by epilepsy surgery, initially sent out an e-mail to its members containing a description of the study, an invitation to participate, and the survey link to the parents of children who had a cerebral hemispherectomy and agreed to be contacted for studies in a past study. In this follow-up study, a survey was sent to all parents who agreed to participate again. A copy of the survey questions can be found in Supplemental Digital Content (See Table E1, https://links.lww.com/WNO/A404).

Demographic information, including age, sex, age of onset of epilepsy, cause of epilepsy, age when patient had a hemispherectomy, and side of hemispherectomy, was collected, and information regarding timeline of improvements, general cognitive development, activity level, diet, and visual and physical therapy, incorporating key components of pedsQL QOL tools for visual impairment such as physical and cognitive functioning. Visual function was assessed by the presence of peripheral field defects, compensatory mechanisms (i.e., ocular misalignment and anomalous head posture), and visual acuity. Whenever possible, visual representations were used on the survey to ensure that survey-takers could understand the questions.

RESULTS

This survey was emailed to 248 parents of children who had a cerebral hemispherectomy, were evaluated in a previous study, and agreed to be surveyed again. Fourty-eight of these patients responded to the current survey.

The demographics of the patients are shown in Table 1. Twenty-one (44%) of the patients were boys. The average age at hemispherectomy was approximately 5 (±4 SD) years, and on average, the time since hemispherectomy was approximately 7 (±5 SD) years. Of the patients, 81% (n = 39) were seizure-free after one surgery and 85% (n = 41) were seizure-free after one or more surgeries. Of the seizure-free individuals, 29% (n = 12) were taking antiseizure medications at the time of the survey. Thirty-four (71%) of them reported an initial visual field defect after surgery, 25 of whom (74% of those with initial defects) reported some sort of subjective improvement in visual field defects over time. The VF improvements were also characterized to be first manifested as less scanning for an item/improved object location, improvement in exotropia/esotropia, less physical collisions, and improvement in reading. In addition, all of the patients with visual field defects used at least one compensatory mechanism, such as head tilting and squinting to accommodate such visual field defects, according to their parents. Twenty-eight (58%) of the patients used compensatory head tilting, and 54% (n = 15) of those patients tilted their head to the contralateral side of the surgery. Of individuals with visual field defects, 44% (n = 21) found conditions were exacerbated by certain factors, with most children negatively affected by crowds/congestion, light/darkness, and fatigue/illness. Sixteen (33%) reported improvement over time with 4% (n = 2) seeing improvements immediately, 8% (n = 4) from 6 to 8 months later, 4% (n = 2) by 1 year, 10% (n = 5) by 2 to 3 years, and 6% continuously (n = 3).

TABLE 1. - Characteristics of Patients Demographics, Post HH Seizures, Defects, Improvements, and lifestyle factors
Avg Max min Std Dev
Demographics
 Male 44% (n = 21)
 Female 56% (n = 27)
 Annual income 102,821 300,000 20,000 64,479
 Age at hemispherectomy 5 13 0.125 4
 Time since hemispherectomy 7 24 0.33 5.62
Seizure free
 Seizure-free after 1 surgery 81% (n = 39)
 Seizure-free after 1 + surgery 85% (n = 41)
 Child taking antiseizure medications? 46% (n = 22)
Visual field defects after surgery and improvements over time
 Initial Visual field defect after surgery (not including patients who had a VF defect before surgery) 71% (n = 34)
 No improvements in VF defects over time 48% (n = 23)
 Little improvement in VF defects over time (25%) 21% (n = 10)
 Moderate VF improvement (50% better) 6% (n = 3)
 Complete VF improvement (100% better) 2% (n = 1)
 Other (unknown VF improvement or being well-compensated or compensated for) 13% (n = 6)
Compensatory mechanisms for VF defects
 Head tilted/turned to the right 29% (n = 14)
 Squinting 2% (n = 2)
 Head tilted/turned to the left 40% (n = 19)
 No compensatory mechanisms 21% (n = 10)
Situations or conditions that improve or negatively affect VF defect
 No 56% (n = 27)
 Light/Darkness 8% (n = 4)
 Crowds/Congested/new environments 19% (n = 9)
 Purposeful placement of items in visual field 6% (n = 3)
 Fatigue/illness 4% (n = 2)
 Reading 6% (n = 3)
Timeline of improvement
 None/NA 67% (n = 32)
 Immediate to 1 month 4% (n = 2)
 6–8 months 8% (n = 4)
 1 year 4% (n = 2)
 2–3 years 10% (n = 5)
 Continuous 6% (n = 3)
How did VF improvements first manifest
 None/NA 65% (n = 31)
 Less scanning for an item/improved object tracking, manipulation, and visual attention 13% (n = 6)
 Improvement in exotropia/esotropia 10% (n = 5)
 Less physical collisions 8% (n = 4)
 Improvement in reading 4% (n = 2)
Decrease in visual acuity after surgery
 Yes 56% (n = 27)
 No 44% (n = 21)
Improvement in visual acuity over time
 No 27% (n = 13)
 n/a 44% (n = 21)
 <25% 15% (n = 7)
 Around 50% 6% (n = 3)
 Around 100% 4% (n = 2)
 Other (eg still being assessed) 4% (n = 2)
Strabismus after surgery
 Right esotropia 8% (n = 4)
 Left esotropia 2% (n = 1)
 R/L alternating esotropia 4% (n = 2)
 Right exotropia 19% (n = 9)
 Left exotropia 23% (n = 11)
 R/L alternating exotropia 4% (n = 2)
 No 29% (n = 14)
 Eso/Exotropia mostly corrected by surgery 10% (n = 5)
Situations or conditions improve or negatively strabismus
 No 25% (n = 12)
 N/a 27% (n = 13)
 fatigue/illness 27% (n = 13)
 Bright lights 2% (n = 1)
 Strabismus surgery 8% (n = 4)
 Viewing stationary objects helps 4% (n = 2)
 Prism glasses/eye patching helps 6% (n = 3)
Improvement in visual acuity over time
 No 23% (n = 11)
 n/a 35% (n = 17)
 <25% 10% (n = 5)
 Around 50% 6% (n = 3)
 Around 100% 13% (n = 6)
 Improvement only after surgery 13% (n = 6)
Cognitive development
 Learning difficulties 69% (n = 33)
 Reading difficulties 50% (n = 24)
 Behavioral problems 40% (n = 19)
 Attentional deficits 48% (n = 23)
 Memory deficits 40% (n = 19)
 Psychiatric conditions 8% (n = 4)
 Good cognitive development 10% (n = 5)
 Global deficits/Disabilities 13% (n = 6)
 Unknown (eg too young to tell) 6% (n = 3)
General activity level after surgery
 30 min–1 hour/d 46% (n = 22)
 –3 to 4 times/wk 31% (n = 15)
 −1 time/wk 10% (n = 5)
 −2 times/mo 2% (n = 1)
 −1 time/mo 0% (n = 0)
 No activity 15% (n = 7)
Vision/Physical therapy
 Visual therapy (eg eye patching, tracking activities) 48% (n = 23)
 Physical therapy (e.g., aqua therapy, bike riding, swimming, baseball, running, stretching) 79% (n = 38)
 No 2% (n = 1)

Twenty-seven (56%) patients reported a decrease in visual acuity after surgery with 44% (n = 12) of those patients experiencing some level of improvement over time. Seventy-one percent of patients reported strabismus after surgery (n = 34) with 59% (n = 20) experiencing some level of improvement over time. Twenty (63%) of the patients reported exotropia. Of these patients 50% (n = 10 out of 20) demonstrated exotropia contralateral to the side of hemispherectomy. Seven (15%) patients demonstrated esotropia, and of these patients, 29% (n = 2) developed esotropia ipsilateral to the side of hemispherectomy, which is believed to be compensatory. Cognitive development was also assessed; 69% (n = 33) of patients reported learning difficulties, 50% (n = 24) reported reading difficulties, 40% (n = 19) reported behavioral problems, 48% (n = 23) reported attentional deficits, 40% (n = 19) reported memory deficits, 8% (n = 4) reported psychiatric conditions, and 13% (n = 6) reported global deficits/disabilities. Of note, only 13% of patients (n = 6) reported good cognitive development.

Of the patients, 48% (n = 23) received some sort of vision therapy (e.g., eye patching, tracking activities), and 79% (n = 38) received physical therapy (e.g., aqua therapy, bike riding, swimming, baseball, running, stretching). Ninety-one percent of the patients with improvements in visual field,,visual acuity, and/or strabismus over time also received “vision therapy,” although the type of therapy was not specified. Diet and general level of activity were also assessed; however, no distinguishing correlations between these variables and improvement in visual defect, acuity, or alignment were found.

In a multivariate regression analysis, greater age at hemispherectomy was found to almost significantly predict strabismus (P = 0.055) (Table 2). In addition, the contribution of surgery, gender, socioeconomics, vision therapy, and physical activity to perceived visual field/visual acuity improvements over time was explored. Lower age at surgery was associated with greater subjective visual field defect improvements (P = 0.045), and parental reported vision therapy predicted greater subjective visual field defect improvements (P = 0.00269) (Table 2). None of the factors of age, gender, socioeconomics, vision therapy, activity, strabismus, visual field defect, visual field improvement, and strabismus improvement consistently predicted any of the components of cognitive development explored.

TABLE 2. - Multivariable Regression Analysis of Predictors on Strabismus, Strabismus and Visual Field Defect Improvements, and Cognitive Development
Endpoint Predictors/Factors Estimate P
Strabismus Age −2.26 0.055832
Strabismus improvements Age 1.51 0.138
Gender −0.078 0.9379
Socioeconomics −0.125 0.901
Vision therapy −1.46 0.151
Physical activity 0.218 0.829
Visual field defect improvements Age −2.064 0.045*
Gender −0.552 0.583
Socioeconomics −0.448 0.656
Vision therapy 3.17 0.00269*
Physical activity −1.41 0.166
Cognitive development Age −0.671 0.506
Gender −0.780 0.439
Socioeconomics −0.569 0.572
Vision therapy 1.2432 0.220
Physical activity 0.683 0.498
Strabismus 0.780 0.439
Visual field defect −1.32 0.194
Visual field defect improvement 0.924 0.360
Strabismus improvement 0.499 0.62
*P value < 0.05.

We also sought to explore whether those who were seizure-free reported differences in subjective observations of visual outcomes by parents. Of the individuals who were seizure-free and taking antiseizure medications (n = 22), 45% had subjective VF defects (n = 10), 23% (n = 5) had strabismus, 9% (n = 2) had visual field improvements, and 23% (n = 5) had strabismus improvements. Of the individuals who were seizure-free and not taking meds (n = 26), 69% (n = 18) had VF defects, 65% (n = 17) had strabismus, 31% (n = 8) had VF improvements, and 27% (n = 7) had strabismus improvements. However, differences between the groups in relation to VF defects (P = 0.313), strabismus (P = 0.353), VF improvements (P = 0.405), and strabismus improvements (P = 0.373) were nonsignificant.

DISCUSSION

This study represents one of the largest cohorts to date looking at patient-reported visual outcomes years after cerebral hemispherectomy. Although the visual fields and strabismus were not directly measured in this study, the results of this study speak to the evolution of subjective visual field defects and strabismus over time. In this study, most patients reported strabismus and/or visual field defects. However, more than half of each cohort reported subjective improvements over time according to a survey of their parents. More than half developed compensatory mechanisms (exotropic strabismus and ipsilateral esotropic strabismus) presumably to enhance function visual field. Most patients were seizure-free after surgery, and less than one third of those patients were concurrently taking antiseizure medications. Of individuals with visual field defects, 52% reported subjective improvements over time, most by 5 years after hemispherectomy, manifesting as decreased physical collisions, improved object tracking etc. Of individuals with strabismus, more than half achieved improvements over time. The results also characterized the development of improvements, and certain logical yet previously unexplored conditions (fatigue, illness, bright lights, crowds, and mobile objects) were found to exacerbate defects.

As of yet, the global cognitive developments of individuals who received hemispherectomies have been relatively unexplored. The results that only 12.5% of patients reported good cognitive development, with the rest citing some level of learning difficulties, reading difficulties, behavioral problems, attention deficits, memory deficits, and psychiatric conditions are particularly concerning. Although hemispherectomies may be the only treatment option for unilateral intractable epilepsy (5), it is important to consider that patients may not only experience visual field defects and strabismus, but also potentially debilitating cognitive development defects that may greatly affect quality of life. Although it is impossible to distinguish whether these diagnoses were present before the hemispherectomy or are part of the natural history of the childrens' underlying diseases in this study, these results speak to the importance of considering prophylactic cognitive development and behavioral therapy to attempt to mitigate these difficulties in our patients lives whether or not they undergo hemispherectomy. These data also suggest that visual therapy should be further explored as a method to facilitate visual field defect and strabismus improvements. In this study, parental-reported therapies (consisting of eye-patching/visual tracking activities, prism glasses, etc.) were found to significantly predict subjective parent-reported visual field defect improvement. However, without actual visual field testing, it is impossible to note whether there was true objective improvement in the visual field of any of these patients. Furthermore, patient-reported improvement may be biased by parents' expectations of outcomes after hemispherectomy and therapy.

These findings are in line with previous studies, which although limited by low statistical power and time to follow-up, have demonstrated similar outcomes. Devlin et al showed that at postoperative follow-up after hemispherectomies, 52% of children were seizure-free, 9% reported rare seizures, 30% showed a greater than 75% reduction in seizures, and only 9% showed less than a 75% reduction in seizures or no improvement at all, slightly lower than the result in this study that 85.42% of patients were seizure-free after hemispherectomy (6). However, postoperative follow-up studies on visual field defects in particular were lacking. Similarly, Koenraads et al (7)sought to determine the visual outcome and prevalence of compensatory mechanisms in children who had undergone hemispherectomy by retrospectively reviewing postoperative ophthalmic examination of visual fixation, visual acuity, visual fields, optic discs, head posturing, ocular alignment, and cognitive development. The results of this study of patient-reported outcomes were consistent with Koenraads et al (7) who found anomalous head posturing and constant or intermittent XT contralateral to the side of hemispherectomy in 53% and 38% of the children, respectively. The results of this study are also consistent with previous studies that have found homonymous hemianopia in most posthemispherectomy children (6); however, our study does not just focus on long-term seizure-free rates, but instead aims to define parent-reported visual and cognitive outcomes (8,9). It is important to note that although previous studies have evaluated hemispherectomy outcomes, typically studies have been limited to retrospectively viewed follow-ups of only few years. Conversely, although reliant on subjective reports, in this study, the average time since hemispherectomy in this population was 7 years, allowing us unique insight into global development after the surgery. Of note, Handley et al (10) uniquely chronicle visual function 20 years after childhood hemispherectomy for intractable epilepsy, and demonstrate that adults after hemispherectomy in childhood may have better visual function in the eye ipsilateral to the side of hemispherectomy over time, with evidence of reorganization to accommodate for postoperative hemispherectomy, similarly suggested by patient-reported visual improvements in this study; however, Handlet et al was limited by a small cohort of 6 patients.

One major limitation of this study is the method of data retrieval. Although the survey study allowed us to follow the largest cohort size of hemispherectomy patients explored over a period of approximately 5 years to date, it is limited by subjective reports, potential ambiguity of responses, and lack of formal ophthalmic evaluations including visual fixation, visual acuity, visual fields, optic discs, ocular alignment, retinal nerve fiber layers, etc. In addition, patient-reported outcomes may be further influenced by parental counseling and expectations of postoperative recovery. However, previous studies looking at compensatory mechanisms have primarily been retrospective, lacking detailed descriptions of abnormal head posture and ocular alignment and have suffered from small sample size and inadequate time to follow-up. Furthermore, subjective measures have been shown to classify visual disability, and have been proven to correlate with objective visual performance in a variety of ophthalmologic studies ranging from visual field size in brain lesioned patients to ocular torsion and macular degeneration (11–13). Therefore, although limited in its clinical description of particular visual changes after hemispherectomy, this study is impactful in its ability to characterize abnormal head posture and ocular alignment in a large cohort of patients as characterized by their families over a significant period of time.

The longitudinal nature of this study allowed us to uniquely characterize patient-reported improvements over time, and suggest that future studies further investigate the role of vision therapy on improving visual field defects. In addition, these longitudinal data suggest that cognitive developments, which are as of yet unexplored, should be considered in management of hemispherectomy patients. Finally, these data should provide motivation for a larger longitudinal study in which patients are examined by ophthalmologists and neurologists to fully ascertain changes in their visual function using qualitative and quantitative measures.

STATEMENT OF AUTHORSHIP

Category 1: a. Conception and design: E. A. Meer, M. F. Chen, M. Jones, G. W. Mathern, and S. L. Pineles; b. Acquisition of data: E. A. Meer, M. F. Chen, and M. Jones; c. Analysis and interpretation of data: E. A. Meer, M. F. Chen, M. Jones, G. W. Mathern, and S. L. Pineles. Category 2: a. Drafting the manuscript: E. A. Meer; b. Revising it for intellectual content: E. A. Meer, M. F. Chen, M. Jones, G. W. Mathern, and S. L. Pineles. Category 3: a. Final approval of the completed manuscript: E. A. Meer, M. F. Chen, M. Jones, G. W. Mathern, and S. L. Pineles.

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