Disclaimer: This article is a preprint and has not yet undergone peer review. Findings and conclusions are preliminary and subject to revision. Reader discretion is advised.
Abstract
Hemispherectomy, a surgical procedure where half of the brain is partially
removed, completely separated, or disconnected from the other hemisphere, has been used as a treatment for persistent, uncontrollable seizures with associated hemiplegia for over 90 years. However, researchers started studying its cognitive effects decades later in 1950. Since then, multiple studies have come out questioning cognition after hemispherectomy and its relevance to age and location. This comprehensive review focuses on the most prevalent cognitive effects after hemispherectomy while attempting to find significant correlations and gaps in the recent existing literature. Ultimately, it found that memory needs the whole, unaltered brain to function properly; cognitive effects after hemispherectomy are correlated with multiple factors like etiology, age, surgery location, and pre-existing abnormalities; and cognitive ability after surgery occupies a broad spectrum. This study also highlights the need for robust, controlled data on hemispherectomy patients to increase our understanding of the brain and improve patients’ lives. Furthermore, it serves as a guide for topics relevant to neurology that need additional studying.
Introduction
Hemispherectomy was first described around 95 years ago as a treatment for
gliomas by Walter Dandy (Bahuleyan et al. 2012). Around 6 decades later in 1990, Rasmussen significantly decreased the mortality rate after surgery by introducing functional hemispherectomy, a surgical procedure emphasizing minimal brain removal and maximal white matter disconnections. However, despite the decrease in the mortality rate of the procedure, the cognitive, behavioral, and clinical effects of hemispherectomy had yet to be addressed. To address this, in 1992, physicians Charles E. Polkey and Faraneh Vargha-Khadem studied the cognitive outcomes after hemispherectomy in humans and noticed favorable effects in the long-term postoperatively. This sparked an examination of the cognitive effects of hemispherectomy in comparison to age, surgical procedure, and etiology. Currently, there are multiple studies regarding cognitive ability after the surgery. This review will explore the most prevalent cognitive effects after hemispherectomy while finding correlations and possible gaps in the recent existing literature.
Background
Hemispherectomy is a surgical procedure where one hemisphere of the brain is either completely removed, partially separated, or disconnected from the other hemisphere (UCLA health system, Hemispherectomy). It is performed on patients experiencing severe, debilitating seizures and who are unresponsive to antiepileptic medications. These persistent seizures can be due to multiple diseases or abnormalities. In the studies analyzed in this review, the seizures were due to Rasmussen’s encephalitis, vascular malformations, cortical dysplasia and pre-existing contralateral abnormalities.
Rasmussen’s encephalitis is a rare disease where there is inflammation on half of the brain and is characterized by hemiplegia, paralysis on half of the body; severe, persistent seizures; and a deteriorating cognitive state (Ellerington et al., 2003). While Rasmussen’s encephalopathy affects one hemisphere of the brain, cortical dysplasia, a brain defect in which the top layer of the brain is organized abnormally, can affect both the hemispheres and cause debilitating seizures (Children’s health, Cortical Dysplasia). Additionally, these diseases and abnormalities can be classified as progressive pathologies or developmental pathologies. Progressive pathologies are diseases like Rasmussen’s encephalitis which have a worsening prognosis while developmental pathologies are defects like cortical dysplasia which involve impairments in a child’s cognitive, motor, and behavioral development (Jacques, 2023; MaineHealth, Developmental Disorders).
Observation
In the studies used in this review, there were ranges of differences in etiology,
pre-existing abnormalities, surgical procedures, and age allowing the patients’ cognitive abilities to occupy a broad spectrum. However, correlations and patterns managed to manifest at certain times.
Etiology
The following studies showed that the underlying pathology was a strongly
associated predictor of a patients’ cognitive skills after hemispherectomy. For example, the average intelligence quotient (IQ) after surgery for patients with Rasmussen’s Encephalitis or vascular malformations was in the 70s while the average IQ after surgery for patients with cortical dysplasia was in the 30s (Pulsifer et al. 2004). Another study reports hemispherectomy in childhood or adolescence due to one diseased hemisphere with associated hemiplegia yields desirable outcomes not only cognitively but also clinically (Devlin et al. 2003). Devlin’s (2003) study gives additional explanation on why Rasmussen’s Encephalitis and vascular malformation patients observed a higher IQ than cortical dysplasia patients in Pulsifer’s (2004) study. Both the Rasmussen’s encephalitis and vascular malformation patients were characterized by one affected hemisphere with associated hemiparesis while cortical dysplasia patients often had both hemispheres affected. Additionally, Devlin’s (2003) research is supported by a study in which pre-existing contralateral magnetic resonance imaging (MRI) abnormalities generally led to a more affected brain with a limited ability to mediate development after hemispherectomy (Schooneveld et al. 2016). It demonstrated how defects in the unaffected hemisphere impact the ability of the brain as a whole in recovering from surgery and provided additional support for Devlin’s claim that patients with one affected hemisphere and associated hemiparesis (e.g. Rasmussen’s encephalitis patients) tend to perform more favorably in terms of cognition.
Although a small study, one study on early hemispherectomy in severe epilepsy raises a substantial similarity amongst the studies: patients with developmental disorders before surgery tend to perform significantly worse in terms of cognition than those with a progressive pathology (Lettory et al. 2007). In the previous studies by Pulsifer (2004), Devlin (2003), and Schooneveld (2016), patients with Rasmussen’s Encephalitis, a progressive pathology, generally observed a more favorable cognition than patients with cognitive dysplasia, a developmental disorder. In Lettory’s study alone, severe IQ impairment was observed in 69% of patients with developmental disorders compared to a significantly less relevant intellectual disability in patients with a progressive pathology (Lettory et al. 2007). Along with Pulsifer’s (2004), Devlin’s (2003), and Schooneveld’s (2016) studies, Lettory’s (2007) study shows that developmental disorders tend to be correlated with a worse cognitive outcome while progressive disorders show the opposite. Overall, these studies provide evidence for the role etiology plays in the cognitive effects of hemispherectomy.
Location of surgery
The location of the surgical procedure (i.e. left hemisphere or right hemisphere) is strongly correlated with the cognitive ability of patients postoperatively. Rasmussen’s encephalitis patients with right hemispherectomy scored with greater proficiency in receptive and expressive language with a mean IQ in the low-average range than patients who had left-hemispherectomy who scored on average in the impaired range (Pulsifer et al. 2004). Likewise, case studies done on 3 patients indicate that those who had left-hemispherectomy performed on average better in nonverbal tasks while those who had right-hemispherectomy performed on average better in verbal tasks (Gott, 2013). Similarly, studies on Rasmussen’s encephalitis patients demonstrate the effect of differences in the location of hemispherectomy on cognition by providing evidence in which the oldest patient who underwent left-hemispherectomy showed greatest weakness in language skills like syntactic abilities while showing greatest strength in nonverbal skills in the short-term (Borne et al. 2022). These studies provide evidence for the effect of the location of surgery on cognitive abilities postoperatively by demonstrating that cognition after hemispherectomy largely relies on the unaffected hemisphere.
However, Borne’s (2022) study emphasizes this weakness in language skills remains early on and adapts as the patient ages; specifically, this adaptation is significantly more favorable when surgery is performed at a young age as the oldest patient had trouble regaining complete cognitive recovery and dealt with persistent disorders after surgery (2013). Overall, it can be seen that patients are better at skills the unaffected hemisphere specializes in and according to Gott’s (2013) study, this disparity between the skills of the unaffected and affected hemisphere increases as the age at which surgery was performed increases (2013).
Age
Certain cognitive effects after hemispherectomy are correlated with the age the patient got surgery. Overall, the studies support that surgery at a young age leads to a more desirable evolution of cognitive skills. While studying Rasmussen’s encephalitis patients after hemispherectomy, researchers observed that the patient who got surgery at 5.5 years of age exhibited normal language and memory performance (except for syntax and inhibition) as early as 1.5 years postoperatively while the patient who got hemispherectomy at 14.0 years of age exhibited partial cognitive recovery with slow reaction times in all tasks (Borne et al. 2022). Likewise, in 3 case studies on patients who had undergone hemispherectomy, a researcher observed in the mature brain, the unaffected hemisphere continues to be more proficient in tasks it is specialized for while in the immature brain, the unoperated hemisphere attempts to incorporate the tasks of the severed half leading to a smaller disparity between verbal and spatial skills but overall, a lower proficiency on most tasks (Gott, 2013). A long-term study over 5 years on early hemispherectomy in catastrophic epilepsy supports earlier surgery for a more favorable evolution cognitively and clinically but highlights the need for larger, controlled data sets (Lettori et al. 2007). Overall, the studies favor earlier surgery for positive cognitive and clinical outcomes.
Spectrum of cognitive effects and most prevalent cognitive effects
Because there is a limitation of controlled, large data sets on the cognitive effects of hemispherectomy, it is difficult to identify meaningful similarities in cognitive effects among hemispherectomy patients. However, there are a few cognitive effects that overlap among studies. For instance, while working with Rasmussen’s encephalitis patients, researchers observed in the long-term, all 3 patients’ syntactic abilities, working memory, inhibition, and attention were weak long-term (Borne et al. 2022). Likewise, in a different study, all patients were found to be deficient in working memory after surgery (Gott, 2013). Because memory is seen to be affected often, these studies could be hinting at the possible effect of hemispherectomy on memory; however, without adequate data (large and controlled studies), an assertion is impossible to make. The studies overall hosted a broad range of cognitive ability after surgery. One study on clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence observed no apparent change in cognitive performance after a median follow up of 2.25 years (Devlin, 2003). By contrast, a study on long-term improvement after functional hemispherectomy observed a significant increase in FSIQ scores in 73.9 % of their patients indicating a significant increase in cognitive ability (Qu et al. 2019). Pulsifer et al., 2004 observed moderate change in cognitive performance. In fact, one study emphasized the broad spectrum of cognitive outcomes after hemispherectomy by observing a huge range of cognitive ability 5 years post operatively; patients ranged from being profoundly intellectually disabled and being completely dependent to having low normal cognition and being reasonably independent (Schooneveld et al. 2016). However, ultimately because of the absence of large and controlled data sets and the presence of multiple confounding variables like etiology, location of the surgical procedure, age, and pre-existing abnormalities, it is difficult to make meaningful and accurate assertions.
Discussion
Due to the lack of robust, controlled studies which yield consistent outcomes, it is difficult to understand the cognitive effects of hemispherectomy which overall ranged from severely impaired to significantly improved after surgery according to the studies analyzed in this review. However, the studies were confounded due to the disregard for the controlling of variables like etiology, location of the surgical procedure, and age. In the future, once there is enough data, it is important to control these variables and observe the cognitive effects without bias.
Additionally, from the limited data analyzed in this review, working memory was found to have been affected after hemispherectomy throughout a few studies. This may indicate that working memory requires the whole, unaltered brain to function properly. Furthermore, because earlier hemispherectomy was found to foster better evolution of cognition, surgeons can now encourage earlier surgery ultimately benefiting their patients. In understanding the role etiology and pre-existing abnormalities play on the cognitive effects after surgery, surgeons can now better anticipate the effects of surgery and inform families while researchers can find ways to prevent these debilitating cognitive effects by focusing their studies on certain patients (e.g. cortical dysplasia patients). Similarly, by now understanding the role the location of the surgical procedure (i.e. left hemisphere vs right hemisphere) plays in the cognitive effects of hemispherectomy, surgeons can anticipate certain cognitive effects and can start notifying the patient’s family and looking for treatment as early as possible; for instance, for a left-hemispherectomy, surgeons should anticipate language impairments prompting him to inform the family and look for specialists who can help treat these issues.
Conclusion
In the end, because of the limitation of large, robust, and controlled data, it is
difficult to reach a definite conclusion. Though, based on the studies analyzed in this review, the following is supported:
- Etiology, age, location of the surgical procedure, and pre-existing abnormalities
all play a role in the cognitive effects of hemispherectomy. - The cognitive effects of hemispherectomy occupy a broad spectrum.
- Memory is found to require the whole, unaltered brain to function properly.
In the future, once there is enough data, it is essential to have robust, controlled studies with which we can not only expand our knowledge on this life-changing surgical procedure and the largely unknown world of the brain but, additionally, help humans live a better quality of life.
References
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