Hemispherectomy

Hemispherectomy is a neurosurgical procedure involving the complete removal or functional disconnection of one cerebral hemisphere, primarily used to treat severe, drug-resistant epilepsy that originates from a single hemisphere in children.^[1] The procedure was first performed in 1928 by Walter Dandy for the treatment of brain tumors, but its application to epilepsy began in 1938 with a case reported by K.G. McKenzie.^[1] Over the decades, techniques evolved from the original anatomical hemispherectomy—which entails full removal of the affected hemisphere—to less invasive functional hemispherectomy and hemispherotomy by the 1990s, aiming to reduce risks such as superficial cerebral hemosiderosis while achieving similar seizure control.^[1] Indications for hemispherectomy typically include pediatric cases of medically refractory epilepsy caused by unilateral conditions like malformations of cortical development (such as hemimegalencephaly), perinatal ischemic strokes, or inflammatory disorders including Rasmussen's encephalitis and Sturge-Weber syndrome.^[1]^[2] In anatomical hemispherectomy, the surgeon removes the frontal, temporal, parietal, and occipital lobes along with the corpus callosum and portions of the basal ganglia if involved; functional variants, including hemispherotomy, instead focus on disconnecting key white matter tracts (e.g., corpus callosum, internal capsule, and optic radiations) with minimal tissue resection to isolate seizure activity.^[1]^[3] Outcomes are generally favorable, with seizure freedom rates ranging from 54% to 90% (Engel class I) in experienced centers, often allowing patients to discontinue antiepileptic medications and improve quality of life.^[1]^[3] However, common long-term effects include contralateral hemiparesis, homonymous hemianopsia, and potential hydrocephalus (occurring in 9-81% of cases, managed with shunts), though cognitive function typically remains stable or improves due to plasticity in young brains, and most patients retain ambulatory ability with rehabilitation.^[1]^[2] Risks such as infection, bleeding, or stroke are present but minimized at specialized pediatric epilepsy centers, with perioperative mortality below 1%.^[3]^[1]

Overview

Definition

Hemispherectomy is a neurosurgical intervention that involves the complete removal or functional disconnection of one cerebral hemisphere to treat severe, drug-resistant epilepsy.^[1] This procedure targets the epileptogenic hemisphere, aiming to halt seizure propagation while preserving the function of the contralateral healthy hemisphere.^[4] The primary goal of hemispherectomy is to eliminate or significantly reduce seizure activity originating from a diseased hemisphere by isolating it from the rest of the brain, thereby improving quality of life for patients with medically intractable epilepsy.^[3] It is typically performed in pediatric cases where seizures arise from widespread hemispheric pathology, such as in Rasmussen's encephalitis.^[1] Anatomically, the cerebral hemispheres control contralateral body functions, including motor, sensory, and visual processing; thus, hemispherectomy on one side predictably results in deficits such as hemiparesis (weakness on the opposite side of the body) and homonymous hemianopsia (loss of half the visual field).^[3] The remaining hemisphere often demonstrates neuroplasticity, particularly in children, allowing partial compensation for lost functions over time.^[1] Unlike lobectomy, which removes only a specific lobe of the brain, or corpus callosotomy, which severs inter-hemispheric connections without resecting tissue, hemispherectomy addresses extensive unilateral epileptogenic networks through broader resection or disconnection.^[4] This distinction makes it a more radical option reserved for cases where focal resections are insufficient.^[5]

Types and Nomenclature

Hemispherectomy procedures are broadly classified into anatomical and functional variants, with the latter encompassing disconnective techniques known as hemispherotomies.^[5] Anatomical hemispherectomy involves the complete surgical removal of one cerebral hemisphere, including the temporal lobe and corpus callosum, to achieve isolation of epileptogenic tissue.^[5] This approach, while historically the first performed, is now rarely undertaken due to substantial risks of intraoperative blood loss and hydrocephalus.^[5] In contrast, functional hemispherectomy, including the hemispherotomy technique, focuses on disconnecting the affected hemisphere from the contralateral side through selective white matter transection, preserving much of the cerebral tissue volume.^[6] This method reduces morbidity compared to full resection while aiming for equivalent seizure control in refractory epilepsy cases.^[6] Subtypes of hemispherotomy include the peri-insular approach, which employs a lateral trajectory centered on the insula for hemispheric deafferentation; the vertical parasagittal technique, involving a midline incision to sever the corpus callosum and ventricular walls; and the transsylvian variant, which accesses disconnection pathways via the Sylvian fissure.^[7]^[6]^[8] The nomenclature has evolved to reflect these technical distinctions: "hemispherotomy" specifically denotes the disconnective procedures that avoid complete tissue excision, distinguishing them from anatomical resections and preventing confusion with less extensive partial lobectomies.^[6] This terminology, popularized in the 1990s, underscores the shift toward functional isolation over radical removal in contemporary practice.^[6] Across all hemispherectomy types, complete isolation requires targeting critical white matter structures, including the insula for cortical disconnection, the internal capsule to interrupt motor pathways, the fornix to sever limbic connections, and the optic radiations to eliminate visual tract communication.^[5]

Historical Development

Early Procedures

The first anatomical hemispherectomy was performed by American neurosurgeon Walter Dandy in 1928, who applied the procedure to five adult patients with glioblastoma multiforme, a malignant brain tumor, rather than for epilepsy treatment.^[9] Dandy's motivation stemmed from the need for radical resection to extend survival in cases where tumors had diffusely infiltrated one cerebral hemisphere, though outcomes were generally poor, with most patients succumbing to disease progression shortly after surgery.^[10] The adaptation of hemispherectomy for epilepsy began in 1938 when Canadian neurosurgeon Kenneth McKenzie performed the procedure on a 16-year-old patient with infantile hemiplegia syndrome and intractable seizures, achieving complete seizure freedom postoperatively.^[11] McKenzie's case highlighted the potential for seizure control in pediatric patients with unilateral brain pathology, drawing on prior observations that children with congenital or early-acquired hemiplegia often exhibited preserved contralateral function despite significant hemispheric damage. This success spurred further exploration, with early reports emphasizing the brain's plasticity in young patients as a key factor allowing functional adaptation after such extensive resection.^[11] During the 1940s and 1950s, hemispherectomy saw a marked increase in application for epilepsy, particularly in children with hemispheric syndromes like infantile hemiplegia or Sturge-Weber syndrome, with surgeons such as McKenzie, Roland Krynauw, and others performing over 260 cases worldwide by the early 1960s.^[12] Initial results were promising for seizure control, with many patients achieving freedom from seizures and improved quality of life, though high complication rates, including immediate postoperative hemorrhage and infection, were frequently noted. The procedure's rationale rested on the understanding that unilateral damage in childhood rarely led to profound functional deficits due to neuroplasticity, enabling the remaining hemisphere to compensate for lost functions over time.^[11] By the 1960s, enthusiasm for anatomical hemispherectomy waned due to accumulating reports of severe complications, including perioperative mortality rates of approximately 5-10% and delayed mortality rates approaching 40% in some series from issues such as superficial siderosis (hemosiderosis) due to chronic blood accumulation in the resection cavity.^[13]^[14]^[15] These risks, often linked to the extensive tissue removal and vascular disruption inherent in the full anatomical approach, prompted a sharp decline in its use until modifications were developed later.^[15] Following a period of decline due to high complication rates in earlier decades, hemispherectomy procedures experienced a revival in the 1980s through the development of modified anatomical approaches and functional techniques aimed at minimizing tissue resection while achieving effective seizure control. Surgeons such as Harold J. Hoffman at the Hospital for Sick Children in Toronto refined anatomical methods to address risks like massive blood loss and hydrocephalus, reporting improved outcomes in cases of Sturge-Weber syndrome with reduced mortality. Concurrently, Theodore Rasmussen at the Montreal Neurological Institute promoted the functional hemispherectomy, introduced in the mid-1970s but popularized in the 1980s, which preserved more brain tissue by focusing on disconnecting epileptogenic pathways rather than complete removal, thereby lowering morbidity.^[16] Key innovations in the 1990s further shifted the paradigm toward disconnective hemispherotomy techniques, emphasizing isolation of the affected hemisphere over extensive resection. Jean-Guy Villemure described the peri-insular (transsylvian) hemispherotomy, a lateral approach that targets the insula to sever corpus callosal, internal capsule, and white matter fibers with minimal cortical excision, as detailed in surgical principles outlined in 1995. Similarly, Olivier Delalande introduced the vertical parasagittal hemispherotomy in 1992, utilizing a paramedian trajectory to disconnect the hemisphere via supratentorial incisions along the midline and insula, preserving vascular structures and reducing operative trauma.^[17] These methods achieved comparable seizure freedom rates to anatomical hemispherectomy—often exceeding 80%—while prioritizing functional isolation.^[16] The adoption of these functional hemispherotomy variants has significantly reduced perioperative morbidity compared to classical anatomical procedures. Early anatomical hemispherectomies often involved blood loss exceeding 1 liter and operative times over 6 hours, whereas modern disconnective techniques typically limit blood loss to 200–500 ml and shorten surgery to 3–4 hours, as evidenced by series reporting mean losses of 387 ml in refined anatomical cases and even lower in functional approaches.^[18]^[19] These improvements stem from limited tissue manipulation and better hemostasis, contributing to their widespread acceptance; by the 2010s, functional hemispherotomy accounted for over 90% of hemispherectomy procedures in specialized centers, reflecting a global standard for pediatric epilepsy surgery.^[5] Advancements in neuroimaging have been instrumental in these refinements since the 1990s, enabling precise preoperative planning and intraoperative guidance. The integration of magnetic resonance imaging (MRI) allowed for detailed visualization of epileptogenic zones and vascular anatomy, while neuronavigation systems facilitated accurate disconnection trajectories, reducing inadvertent injury and improving completeness of isolation.^[5]^[20] The global dissemination of these techniques accelerated in the 2000s through standardized protocols at leading institutions. At Great Ormond Street Hospital in the UK, a multidisciplinary approach incorporating functional hemispherotomy yielded seizure freedom in 52% of 33 pediatric cases treated between 1991 and 1997, with emphasis on long-term neurodevelopmental monitoring.^[21] Similarly, the UCLA Pediatric Epilepsy Surgery Program refined the modified lateral hemispherotomy, reporting blood losses of 200–600 ml and seizure control in over 80% of patients across series spanning the early 2000s, establishing benchmarks for safety and efficacy.^[22]

Indications and Patient Selection

Underlying Conditions

Hemispherectomy is primarily indicated for patients with medically intractable epilepsy originating from diffuse, unilateral hemispheric pathology, where seizures arise from extensive regions of one cerebral hemisphere, often confirmed by neuroimaging and electroencephalography (EEG).^[1] These conditions typically involve early-onset, drug-resistant seizures that significantly impair quality of life, with the procedure reserved for cases where the contralateral hemisphere remains relatively unaffected to preserve function.^[1] Rasmussen's encephalitis represents a classic indication, characterized by progressive unilateral cortical inflammation, likely autoimmune in origin, leading to intractable focal seizures, hemiparesis, and cognitive decline in children.^[23] The condition manifests as epilepsia partialis continua and hemispheric atrophy, making early hemispherectomy ideal to arrest progression and achieve seizure freedom in up to 90% of pediatric cases.^[1] Sturge-Weber syndrome, a congenital neurocutaneous disorder, involves leptomeningeal vascular malformations causing progressive hemispheric ischemia, atrophy, calcification, and epilepsy in 75-80% of affected individuals.^[24] Hemispherectomy is particularly effective in patients with extensive unilateral involvement and pre-existing hemiparesis, often resulting in seizure cessation without further functional deterioration.^[24] Perinatal stroke and hemimegalencephaly are key congenital or early-acquired etiologies; the former involves large hemispheric infarcts leading to gliosis and epilepsy in about 13% of cases, while the latter features abnormal unilateral hemispheric enlargement with cortical dysplasia generating widespread epileptogenic networks from infancy.^[1] Both present with drug-resistant seizures and minimal contralateral involvement, rendering hemispherectomy suitable as it leverages the brain's plasticity in young patients to minimize additional deficits.^[25] Other etiologies include post-traumatic brain injury or infectious processes causing unilateral hemispheric damage, such as encephalitic sequelae, though these are less common and require confirmation of localized seizure onset.^[1] Rare adult cases may stem from tumors or vascular malformations leading to diffuse epilepsy, but indications are limited due to reduced plasticity and higher risks.^[1] The pathophysiological basis for hemispherectomy demands that seizures originate from more than two-thirds to the entire affected hemisphere, as determined by multimodal evaluation including MRI for structural anomalies and EEG for ictal/interictal patterns, ensuring the procedure targets the epileptogenic zone without compromising bilateral function.^[26]

Diagnostic Evaluation

The diagnostic evaluation for hemispherectomy begins with a comprehensive epilepsy assessment to confirm that seizures originate from a single hemisphere and are medically intractable. Video-EEG monitoring is the cornerstone of this process, capturing typical seizure events during inpatient or outpatient sessions to analyze semiology, onset zones, and electrographic patterns, thereby localizing epileptogenic activity to one hemisphere.^[27]^[28] This monitoring, often lasting several days, helps differentiate epileptic from non-epileptic events and excludes bilateral involvement, which would contraindicate the procedure.^[29] Neuroimaging plays a critical role in identifying structural and functional abnormalities in the affected hemisphere. High-resolution MRI is routinely performed to detect lesions such as cortical dysplasia, hemimegalencephaly, or perinatal infarcts, with protocols optimized for epilepsy (e.g., thin-slice coronal and temporal lobe sequences) revealing abnormalities in up to 90% of candidates.^[27] Complementary functional imaging, including interictal PET to identify hypometabolism and ictal SPECT with SISCOM analysis to map hyperperfusion during seizures, further confirms hemispheric involvement and assesses the extent of dysfunctional tissue.^[27]^[29] These modalities ensure the contralateral hemisphere is relatively preserved, guiding surgical candidacy. Functional assessments evaluate baseline cognitive, motor, and language abilities to predict postoperative outcomes and inform risks. Neuropsychological testing provides a detailed profile of memory, attention, executive function, and hemiparesis, establishing pre-surgical baselines that correlate with better recovery in younger patients due to neuroplasticity.^[27]^[28] The traditional Wada test, which temporarily anesthetizes one hemisphere to assess language dominance, is now rarely used in favor of non-invasive fMRI for mapping eloquent areas like language and motor cortex, reducing procedural risks while maintaining accuracy in lateralization.^[30] Hemispherectomy is optimally considered in children under 10 years, when plasticity maximizes functional compensation by the remaining hemisphere.^[31] A multidisciplinary team, comprising epileptologists, neurosurgeons, neuropsychologists, and neuroradiologists, reviews all data in a surgical conference to confirm unilaterality and exclude contraindications such as bilateral epileptogenic zones or non-epileptic paroxysmal events.^[27]^[29] This collaborative approach ensures thorough patient selection, prioritizing those with catastrophic epilepsy where benefits outweigh risks like hemiparesis.^[28]

Surgical Procedure

Preoperative Preparation

Preoperative preparation for hemispherectomy focuses on optimizing the patient's physiological status, ensuring surgical precision, and mitigating risks associated with this extensive procedure, which is most commonly performed in pediatric patients with intractable epilepsy. Medical optimization begins with adjustment of antiepileptic drugs (AEDs), typically continued on the day of surgery to maintain seizure control unless electrocorticography is planned, in consultation with the epileptologist; this approach minimizes perioperative seizures while accounting for potential AED side effects such as hyponatremia or thrombocytopenia, screened via preoperative blood tests including electrolytes, complete blood count, and liver function. Infection prophylaxis involves administration of prophylactic antibiotics, often cefazolin, alongside gastroprotective agents like proton pump inhibitors to prevent stress ulcers; intravenous dexamethasone is routinely given to reduce cerebral edema.^[32] Nutritional support is emphasized, particularly in children with chronic epilepsy, through preoperative assessment and supplementation if malnutrition is present, to support wound healing and immune function.^[32] Anesthesia planning entails general endotracheal anesthesia to facilitate the prolonged operative time, with agents such as propofol, fentanyl, and isoflurane or sevoflurane preferred over nitrous oxide to avoid interference with electrocorticography or increasing intracranial pressure; remifentanil infusion provides analgesia without delaying emergence. Invasive monitoring, including arterial and central venous lines, is standard to track hemodynamics, maintain PaCO2 at 32–34 mmHg for cerebral perfusion, and prevent hypothermia via warmed fluids and forced-air blankets.^[32] Neuromonitoring with somatosensory evoked potentials (SSEPs) and electroencephalography (EEG) is integrated to monitor brain function and detect ischemia during vascular manipulations, while motor evoked potentials (MEPs) may assess contralateral motor pathways.^[33] Cross-matched blood products must be readily available due to anticipated blood loss exceeding 50 mL/kg in many cases. Surgical planning incorporates advanced imaging, such as magnetic resonance imaging (MRI) with three-dimensional (3D) reconstruction to delineate vascular anatomy, including bridging veins via MR venography, and select the optimal approach—whether anatomical or functional hemispherectomy—based on lesion extent and eloquent areas. Neuronavigation systems overlay preoperative MRI onto intraoperative views for precise craniotomy placement, typically in a semi-decubitus position with the head rotated 45 degrees.^[32] Informed consent is obtained after discussing expected deficits, such as contralateral hemiplegia, hemianopia, and potential cognitive impacts, alongside benefits like seizure freedom rates of 60–90%. In pediatric patients, who comprise the majority of candidates, special attention addresses higher transfusion risks, with approximately 37% requiring intraoperative blood products, based on large inpatient database analyses, due to lower blood volume (70–80 mL/kg) and vulnerability to hypovolemic shock; maximum allowable blood loss is calculated preoperatively (e.g., estimated blood volume × [initial hematocrit – target hematocrit]/average hematocrit), and strategies include preoperative anemia correction via iron supplementation or erythropoietin if time permits.^[32]^[34] A pediatric anesthesiologist manages these nuances, including electrolyte balance and temperature control, given children's susceptibility to disturbances.^[32] Timing of surgery is often urgent in progressive conditions like Rasmussen's encephalitis, where early intervention—ideally within 1–2 years of onset—halts hemispheric deterioration and preserves contralateral function, contrasting with more elective scheduling for stable lesions like perinatal strokes. This preparation follows diagnostic confirmation of unilateral epileptogenesis via prior evaluations.

Intraoperative Techniques

The intraoperative techniques for hemispherectomy involve a large frontotemporoparietal craniotomy to expose the affected hemisphere, followed by systematic resection of the frontal, temporal, parietal, and often occipital lobes, with disconnection of the corpus callosum and anterior commissure to isolate the epileptogenic tissue.^[13] This anatomical approach aims for complete removal of cortical and subcortical structures while preserving vascular integrity, typically requiring meticulous subpial dissection to minimize blood loss.^[13] Hemispherotomy variants, which prioritize functional disconnection over extensive resection, include the peri-insular approach, where a craniotomy centered on the insula allows exposure of the peri-insular sulci; this involves seven key stages: patient positioning, operative approach, opercular resection, transventricular callosotomy, fronto-orbital disconnection, anterior temporal disconnection, and posterior temporal disconnection, with subpial resection of the insular cortex and white matter tracts.^[35] The vertical hemispherotomy uses a smaller parietal craniotomy (approximately 4 × 4 cm) to access the cingulate gyrus and lateral ventricle, enabling total corpus callosotomy via an interhemispheric route, disconnection of the lateral thalamic rim along the choroid plexus, and resection of parenchyma from the inferior choroidal point to the foramen of Monro, including fornix sectioning.^[36] In the transsylvian approach, a keyhole craniotomy (4 × 4 to 5 × 6 cm) over the sylvian fissure facilitates transsylvian exposure of the circular sulcus, uncoamygdalohippocampectomy, transventricular callosotomy, and mesial frontobasal and occipitoparietal disconnections, sparing most middle cerebral artery branches while coagulating hippocampal vessels.^[8] Recent advances include minimally invasive variants such as laser interstitial thermal therapy (LITT)-assisted hemispherotomy, which employs MRI-compatible laser probes for targeted disconnection of white matter tracts, reducing operative time, blood loss, and tissue trauma while achieving comparable seizure outcomes in select pediatric cases, as demonstrated in procedures reported as of 2024.^[37] Common steps across techniques begin with dural opening after craniotomy, followed by vascular control to preserve pericallosal and posterior cerebral arteries while transecting non-essential vessels, and complete de-afferentation through transection of the corona radiata, superior longitudinal fasciculus, uncinate fasciculus, and fimbria fornix.^[36] Procedures typically last 4 to 8 hours, with intraoperative monitoring via ultrasound for ventricular guidance, neuronavigation for precise tract disconnection, electrocorticography on the insula to assess residual epileptiform activity, or 3-T MRI with diffusion tensor imaging to confirm complete disconnection.^[38]^[39]^[40] Closure emphasizes hemostasis through bipolar coagulation and hemostatic agents, duraplasty with synthetic grafts if needed, and intracranial pressure management via ventricular drainage or osmotherapy to prevent postoperative swelling.^[8]

Complications and Risks

Surgical Risks

Hemispherectomy, whether anatomical or functional variants like hemispherotomy, carries several immediate perioperative risks, primarily due to the extensive nature of the procedure involving significant brain tissue removal or disconnection. These risks have diminished with modern techniques and multidisciplinary management, but they remain critical considerations, especially in pediatric patients where the majority of procedures occur.^[41] Hemorrhage represents a major intraoperative hazard, particularly in anatomical hemispherectomy, where extensive resection can lead to substantial blood loss, averaging around 387 ml and up to 500 ml in some cases. Approximately 28% of patients require blood transfusion due to significant intraoperative bleeding, with intracerebral hemorrhage occurring in 9% overall (rising to 33% in anatomical procedures) and extra-axial collections needing evacuation in 8%. Management strategies include preoperative planning for fluid resuscitation, intraoperative monitoring, and staged resections in high-risk cases to mitigate hemodynamic instability from sudden blood loss.^[18]^[41] Infection risks, including wound infections and meningitis, affect about 11% of patients perioperatively. These are largely prevented through prophylactic intravenous antibiotics administered pre- and postoperatively, alongside strict sterile techniques.^[41] Anesthetic complications are prominent in pediatric cases, where massive and precipitous blood loss can cause blood pressure instability and require aggressive fluid resuscitation and inotropic support during and immediately after surgery. Advances in pediatric neuroanesthesia have helped stabilize these issues, though young age remains a vulnerability factor.^[42] Acute neurological events, such as stroke from vascular injury during tissue disconnection or intraoperative seizures, pose additional immediate threats, though their incidence is low (under 5% in reported series) and often managed with real-time neuromonitoring. Cranial nerve deficits, as a related acute event, occur in 11% but have decreased with refined techniques.^[41] Perioperative mortality has improved dramatically, from historical rates exceeding 30% in the 1970s due to hemorrhage and infection, to less than 2% in modern eras with modified procedures; overall rates stand at 5%, higher (7%) for anatomical hemispherectomy than hemispherotomy (3%). Recent 2025 series confirm minimal perioperative complications with these techniques.^[41]^[43]

Long-Term Complications

Hydrocephalus represents one of the most prevalent long-term complications following hemispherectomy, occurring in approximately 23% of cases across large multi-institutional cohorts. This condition arises primarily from the accumulation of blood products and debris within the resection cavity, which can obstruct cerebrospinal fluid (CSF) pathways and lead to ventricular enlargement, with onset ranging from immediate postoperative periods to over eight years later. Anatomic hemispherectomy techniques are associated with a higher risk (up to 30%) compared to functional approaches (around 20%), and prior brain surgeries further elevate the odds by about 1.7-fold. Management typically involves the placement of a ventriculoperitoneal (VP) shunt to divert excess CSF, which was required in over 99% of affected patients in reviewed series, alongside close monitoring for shunt malfunction.^[44] Superficial cerebral hemosiderosis, characterized by iron deposition from chronic subacute bleeding into the resection cavity, has emerged as a significant but now rarer delayed complication, historically affecting up to 33% of patients undergoing anatomic hemispherectomy. This iron-laden hemosiderin accumulation in the meninges, ependyma, and superficial brain layers can trigger progressive neurological decline, including cerebellar ataxia, sensorineural hearing loss, and pyramidal tract involvement, often compounded by secondary hydrocephalus. In contemporary practice, the incidence has dropped to less than 5% due to the adoption of less invasive disconnective procedures like hemispherotomy, which preserve vascularized brain tissue and minimize large open cavities prone to repeated hemorrhage. Treatment focuses on supportive care for symptoms, with surgical interventions reserved for severe cases involving shunt placement or cavity lining removal.^[1] Endocrine disturbances constitute another important long-term sequela, affecting roughly 12.6% of pediatric patients post-hemispherectomy, often stemming from inadvertent hypothalamic or pituitary involvement during surgery. These may manifest as precocious puberty (in about 5.7% of cases), diabetes insipidus (0.8%), excessive weight gain (16.4%), or multiple hormonal deficits leading to growth impairments and metabolic imbalances. The proximity of surgical trajectories to hypothalamic structures heightens this risk, particularly in procedures involving deep resections, and the presence of postoperative hydrocephalus further amplifies vulnerability to up to 30% incidence of endocrinopathies. Management entails multidisciplinary endocrine evaluation, hormone replacement therapy, and serial assessments to mitigate developmental impacts.^[45] Recurrent infections pose an ongoing concern in the years following hemispherectomy, particularly among those requiring VP shunts for hydrocephalus, where shunt-related complications can lead to episodes of infection. Risks are heightened in patients with pre-existing shunts undergoing hemispherectomy. Treatment involves prompt antibiotic therapy, potential shunt revision or removal, and preventive strategies like prophylactic antimicrobials during revisions.^[46] Long-term monitoring is essential to detect and manage these delayed complications, typically involving magnetic resonance imaging (MRI) to assess for hydrocephalus progression, hemosiderosis, or structural changes, alongside routine neurological examinations for subtle deficits like ataxia or endocrine symptoms. This surveillance protocol, informed by multi-institutional data showing delayed onsets, enables timely interventions such as shunt adjustments or hormonal therapies, thereby optimizing quality of life.^[44]

Outcomes and Prognosis

Seizure Control

Hemispherectomy is highly effective for achieving seizure freedom in pediatric patients with drug-resistant hemispheric epilepsy, with success rates typically ranging from 60% to 90% classified as Engel Class I (seizure-free) at 1 to 2 years post-surgery.^[47]^[48] These outcomes are sustained long-term in approximately 70% to 80% of cases, though rates may decline to around 63% beyond 5 years in some cohorts due to late relapses.^[19]^[49] Key predictors of favorable seizure control include surgery performed at an early age, particularly before 3 years, which enhances the likelihood of Engel Class I outcomes by allowing better adaptation and reducing established epileptic networks.^[50] Complete disconnection of the affected hemisphere, as achieved in modern hemispherotomy techniques, also significantly improves seizure freedom rates compared to partial resections, with vertical approaches yielding up to 81% success versus 71% for lateral methods.^[51] Failure to achieve seizure control occurs in 10% to 20% of cases, often due to incomplete isolation of epileptogenic tissue or propagation to the contralateral hemisphere.^[52]^[53] Such failures may necessitate reoperation, with completion procedures restoring freedom in about 35% of revisited patients.^[54] Post-surgery, many patients successfully discontinue antiepileptic drugs (AEDs), often starting weaning 3 to 6 months after the procedure if seizure-free, with recurrence rates around 20% linked to withdrawal but frequently manageable through resumed medication or targeted interventions.^[55]^[52] Recent meta-analyses from the 2020s, focusing on pediatric cohorts, report seizure freedom rates approaching 85% in well-selected cases, underscoring the procedure's reliability with refined techniques.^[56]^[57] A 2024 study at a major pediatric center found that the effectiveness of hemispherectomy in achieving long-term seizure control has improved over time.^[50]

Functional Impacts

Following hemispherectomy, patients often experience changes in motor function due to the disconnection or removal of one cerebral hemisphere, which controls contralateral body movements. Pre-existing hemiparesis typically worsens in the immediate postoperative period but tends to stabilize over time, with gross motor function remaining unchanged in approximately 60% of cases and improving in 27% through neural plasticity mechanisms that allow the remaining hemisphere to compensate.^[58] In one series of 33 pediatric patients, hemiplegia was unchanged in 67%, improved in 15%, and worsened in 18%, with no loss of ambulatory independence in the majority.^[21] Ambulatory status is preserved or enhanced in most children, particularly when preoperative function is relatively intact, though up to 34% may experience mild worsening, often requiring temporary assistive devices.^[59] Visual field deficits are a common consequence, primarily due to disruption of the optic radiations in the resected or disconnected hemisphere. Nearly all patients develop a contralateral homonymous hemianopia, affecting 80-90% or more in reported series, resulting in loss of half the visual field on the opposite side of the body.^[60] This deficit is typically permanent but can be partially compensated through adaptive strategies like head turning or scanning, with visual acuity in the intact field remaining stable in about 43% of cases and worsening in 45%.^[59] Cognitive outcomes vary by age at surgery and underlying pathology, but hemispherectomy generally results in modest declines rather than severe deterioration. Average full-scale IQ drops by 10-15 points in many patients, though changes are often less than 15 points overall, with 58% showing no decline across tested domains and 31% demonstrating improvements in problem-solving abilities.^[61] Language functions are largely preserved when the dominant hemisphere is spared, particularly in younger children who benefit from greater plasticity, allowing the nondominant hemisphere to assume verbal processing roles.^[21] Quality of life typically improves post-hemispherectomy, driven by enhanced independence and fewer medical interventions. In one cohort, 85% of patients reported better overall quality of life, with gains in daily functioning and reduced hospitalizations linked to seizure freedom.^[62] Behavioral improvements occur in up to 92% of those with preoperative issues, including reduced aggression and better social engagement, contributing to greater family satisfaction and school participation.^[21] Intensive rehabilitation plays a crucial role in mitigating functional deficits, especially in children where brain plasticity is more pronounced. Early postoperative physical, occupational, and speech therapy—often involving constraint-induced movement or robotics-assisted training—promotes adaptation, with studies showing significant recovery in motor skills even years after surgery.^[63] In pediatric series, such programs lead to stabilized or improved adaptive functioning in 85% of cases, emphasizing the need for multidisciplinary follow-up to optimize long-term outcomes.^[64]

Research and Advances

Recent Studies

Recent meta-analyses have documented a significant decline in mortality rates associated with hemispherectomy procedures, dropping from 32% (95% CI: 0.21-0.48) in the 1970s to 2% (95% CI: 0.01-0.05) in the 2020s, based on a systematic review of 124 studies encompassing 1,924 patients.^[41] This improvement is attributed to the evolution toward hemispherotomy techniques and advancements in neuroanesthesia, with overall procedural mortality at 5%, including 7% for anatomical hemispherectomy and 3% for hemispherotomy.^[41] A 2024 retrospective study from The Hospital for Sick Children analyzed 146 pediatric cases of functional hemispherectomy performed between 1987 and 2022, reporting 61% (89/146) achieving long-term seizure freedom (Engel class IA) at a mean follow-up of 209 weeks (range 4–832 weeks), with outcomes improving over time (β = 0.06, p < 0.001).^[50] Cognitive stability was observed in most patients, with only 2 cases of cognitive deficits and 7 cases of speech/language deficits reported, alongside 84% short-term seizure freedom.^[50] Stroke etiology was strongly associated with better long-term seizure freedom (OR 7.50, p = 0.002).^[50] Applications of hemispherectomy in adults remain rare but are increasingly explored in select cases of intractable epilepsy with pre-existing hemiparesis; a 2019 series of 47 adults and adolescents reported 76% achieving Engel class I seizure freedom, with functional outcomes comparable to pediatric cases. Systematic reviews confirm success rates of 50-70% in carefully selected adult patients, emphasizing the procedure's feasibility despite lower overall utilization.^[65] Comparative studies indicate that hemispherotomy offers similar seizure efficacy to anatomical hemispherectomy but with reduced blood loss and complications; for instance, a 2019 analysis reported average blood loss of 387 mL in anatomical procedures versus lower volumes in hemispherotomy approaches, alongside decreased shunt dependence.^[18] A 2023 individual patient data meta-analysis further supported hemispherotomy's advantages, showing no differences in overall complications but higher revision rates for lateral hemispherotomy due to incomplete disconnection.^[51] Approximately 90% of hemispherectomy procedures are performed in children under 18 years old, with etiologic-specific outcomes varying by underlying pathology.^[66] In Sturge-Weber syndrome, a 2023 individual participant data meta-analysis of pediatric cases demonstrated high seizure freedom rates, with hemispheric surgeries achieving favorable outcomes comparable to focal resections, often exceeding 80% Engel class I at long-term follow-up.^[67]

Future Directions

Emerging research is focusing on minimally invasive techniques to perform hemispheric disconnection, such as magnetic resonance-guided laser interstitial thermal therapy (LITT), which avoids traditional open craniotomy and reduces associated risks like hydrocephalus and infection.^[68] Case series have demonstrated LITT's feasibility for complete functional hemispherotomy in pediatric patients, achieving seizure freedom in all cases at follow-up periods of 9 to 16 months, with shorter hospital stays and no need for shunt placements compared to conventional approaches.^[68] For completion hemispherotomy in patients with residual seizures after prior surgery, LITT has significantly reduced mean daily seizure frequency from 8.6 to 1.03, highlighting its potential to minimize surgical trauma while maintaining efficacy.^[68] Future multi-center trials with standardized protocols are needed to optimize patient selection and long-term outcomes for these prototypes.^[68] Integration of targeted therapies, including early explorations of immune-modulating interventions, is being investigated for specific etiologies like Rasmussen's encephalitis to potentially delay or complement surgical disconnection. Hemispherectomy remains the definitive treatment, and precision medicine approaches targeting immune pathogenesis—such as rituximab or other biologics—aim to slow disease progression before surgery. These efforts seek to preserve more functional brain tissue. Advancements in neuroplasticity research emphasize adjunctive strategies like stem cell transplantation and neuromodulation to counteract post-surgical deficits, supported by preclinical data from 2025 models of brain injury. Stem cell grafts, particularly mesenchymal stem cells, have shown promise in rodent epilepsy models by reducing seizure frequency and promoting neural repair through anti-inflammatory effects and enhanced connectivity in the remaining hemisphere.^[69] Non-invasive neuromodulation techniques, such as transcranial direct current stimulation, are under investigation to boost plasticity after large resections. Expansion of hemispherectomy to adults addresses challenges like reduced neuroplasticity, with ongoing studies and outcome registries demonstrating comparable seizure freedom rates to pediatric cases, around 70-80% long-term.^[70] Barriers such as preoperative hemiparesis and older age are being evaluated through multi-institutional data collection, which shows stable functional outcomes despite less adaptive capacity in adults.^[71] Registries tracking longitudinal metrics, including quality of life and plasticity markers, are essential for refining selection criteria and predicting recovery in this population.^[72] Ethical and global challenges in hemispherectomy include limited access in low-resource settings, where shortages of neurosurgeons and imaging infrastructure hinder timely intervention, exacerbating inequities in epilepsy care.^[73] Long-term registries are critical for monitoring rare complications like hemosiderosis or hydrocephalus beyond five years, informing global guidelines and resource allocation in low- and middle-income countries.^[74] Efforts to establish international collaborations aim to improve training and data sharing, ensuring equitable advancements in surgical epilepsy management.^[73]