Anterior Thalamic Stimulation

Anterior Thalamic Stimulation

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is a novel and promising treatment method for patients with drug-resistant epilepsy.

More than 70% of patients implanted with ANT-DBS benefit significantly from this method, i.e., they report seizure-reduction rates higher than 50%

The median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years (p < 0.001).

Long-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population.

Classification of evidence: This long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years. 1).

When focusing on the adverse events reported in a study of stimulation of the anterior nuclei of thalamus (SANTE study), the patients reported paresthesia (18% patients), pain in the implant side (10.9% patients), and infection at the implant site (9.1% patients) 2)

Sobstyl et al. performed a literature search regarding the clinical efficacy of ANT DBS. They discussed the surgical technique of the implantation of DBS electrodes with special attention paid to the targeting methods of the ANT. Moreover, they present in detail the clinical efficacy of ANT DBS, with a special emphasis on the stimulation parameters, a stimulation mode, and polarity. They also report all adverse events and present the current limitations of ANT DBS.

In general, the safety profile of DBS in intractable epilepsy patients is good, with a low rate of surgery, hardware-related, and stimulation-induced adverse events. No significant cognitive declines or worsening of depressive symptoms was noted. At long-term follow-up, the quality-of-life scores have improved. The limitations of ANT DBS studies include a limited number of patients treated and mostly open-label designs with only one double-blind, randomized multicenter trial. Most studies do not report the etiology of intractable epilepsy or they include nonhomogeneous groups of patients affected by intractable epilepsy. There are no guidelines for setting initial stimulation parameters. All the variables mentioned may have a profound impact on the final outcome.

ANT DBS appears to be a safe and efficacious treatment, particularly in patients with refractory partial seizures (three-quarters of patients gained at least 50% seizure reduction after 5 years). ANT DBS reduces most effectively the seizures originating in the temporal and frontal lobes. The published results of ANT DBS highlight promise and hope for patients with intractable epilepsy 3).

A literature review discusses the rationale, mechanism of action, clinical efficacy, safety, and tolerability of ANT-DBS in drug-resistant epilepsy patients. A review using systematic methods of the available literature was performed using relevant databases including Medline, Embase, and the Cochrane Library pertaining to the different aspects ANT-DBS. ANT-DBS for drug-resistant epilepsy is a safe, effective and well-tolerated therapy, where a special emphasis must be given to monitoring and neuropsychological assessment of both depression and memory function. Three patterns of seizure control by ANT-DBS are recognized, of which a delayed stimulation effect may account for an improved long-term response rate. ANT-DBS remotely modulates neuronal network excitability through overriding pathological electrical activity, decrease neuronal cell loss, through immune response inhibition or modulation of neuronal energy metabolism. ANT-DBS is an efficacious treatment modality, even when curative procedures or lesser invasive neuromodulative techniques failed. When compared to VNS, ANT-DBS shows slightly superior treatment response, which urges for direct comparative trials. Based on the available evidence ANT-DBS and VNS therapies are currently both superior compared to non-invasive neuromodulation techniques such as t-VNS and rTMS. Additional in-vivo research is necessary in order to gain more insight into the mechanism of action of ANT-DBS in localization-related epilepsy which will allow for treatment optimization. Randomized clinical studies in search of the optimal target in well-defined epilepsy patient populations, will ultimately allow for optimal patient stratification when applying DBS for drug-resistant patients with epilepsy 4).

Bilateral ANT electrodes were implanted into 18 patients suffering from focal, pharmacoresistant epilepsy. Antiepileptic treatment was kept unchanged from three months prior to operation. The Liverpool seizure severity scale (LSSS) was used to measure the burden of epilepsy.

Results: There was no significant difference between the 2 groups at the end of the blinded period at 6 months. However, when considering all patients and comparing 6 months of stimulation with baseline, there was a significant, 22% reduction in the frequency of all seizures (P = 0.009). Four patients had ≥50% reduction in total seizure frequency and 5 patients ≥50% reduction in focal seizures after 6 months of stimulation. No increased effect over time was shown. LSSS at 6 months compared to baseline showed no significant difference between the 2 groups, but a small, significant reduction in LSSS was found when all patients had received stimulation for 6 months.

Conclusions: Our study supports results from earlier studies concerning DBS as a safe treatment option, with effects even in patients with severe, refractory epilepsy. However, our results are not as encouraging as those reported from many other, mainly unblinded, and open studies 5).

A case of relapsing herpes simplex encephalitis (HSE) as a newly reported and potentially fatal stimulation-related adverse effect following stimulation of the anterior thalamic nucleus (ANT-DBS) accompanied by fever, confusion, and cognitive impairment in a 32-year-old epileptic patient with a history of herpes meningoencephalitis 31 years earlier. The T2-weighted/FLAIR high-signal intensity in the temporal lobe developed at a “distance” from the stimulation target. The positive polymerase chain reaction of herpes virus deoxyribonucleic acid in the cerebrospinal fluid confirmed the diagnosis. The condition improved partially on acyclovir and stimulation stopped. Seizures disappeared and then returned after few months. The unique case report presents a rationale for considering history of herpes encephalitis as a relative contraindication for ANT-DBS, and HSE relapse should be suspected in patients with post-stimulation fever and/or altered consciousness 6).


Salanova V, Witt T, Worth R, Henry TR, Gross RE, Nazzaro JM, Labar D, Sperling MR, Sharan A, Sandok E, Handforth A, Stern JM, Chung S, Henderson JM, French J, Baltuch G, Rosenfeld WE, Garcia P, Barbaro NM, Fountain NB, Elias WJ, Goodman RR, Pollard JR, Tröster AI, Irwin CP, Lambrecht K, Graves N, Fisher R; SANTE Study Group. Long-term efficacy and safety of thalamic stimulation for drug-resistant partial epilepsy. Neurology. 2015 Mar 10;84(10):1017-25. doi: 10.1212/WNL.0000000000001334. Epub 2015 Feb 6. PMID: 25663221; PMCID: PMC4352097.

Fisher R, Salanova V, Witt T, Worth R, Henry T, Gross R, Oommen K, Osorio I, Nazzaro J, Labar D, Kaplitt M, Sperling M, Sandok E, Neal J, Handforth A, Stern J, DeSalles A, Chung S, Shetter A, Bergen D, Bakay R, Henderson J, French J, Baltuch G, Rosenfeld W, Youkilis A, Marks W, Garcia P, Barbaro N, Fountain N, Bazil C, Goodman R, McKhann G, Babu Krishnamurthy K, Papavassiliou S, Epstein C, Pollard J, Tonder L, Grebin J, Coffey R, Graves N; SANTE Study Group. Electrical stimulation of the anterior nucleus of thalamus for treatment of refractory epilepsy. Epilepsia. 2010 May;51(5):899-908. doi: 10.1111/j.1528-1167.2010.02536.x. Epub 2010 Mar 17. PMID: 20331461.

Sobstyl M, Stapińska-Syniec A, Iwański S, Rylski M. Clinical Efficacy and Safety Profile of Anterior Thalamic Stimulation for Intractable Epilepsy. J Neurol Surg A Cent Eur Neurosurg. 2021 Jun 14. doi: 10.1055/s-0041-1725954. Epub ahead of print. PMID: 34126641.

Bouwens van der Vlis TAM, Schijns OEMG, Schaper FLWVJ, Hoogland G, Kubben P, Wagner L, Rouhl R, Temel Y, Ackermans L. Deep brain stimulation of the anterior nucleus of the thalamus for drug-resistant epilepsy. Neurosurg Rev. 2019 Jun;42(2):287-296. doi: 10.1007/s10143-017-0941-x. Epub 2018 Jan 6. PMID: 29306976; PMCID: PMC6502776.

Herrman H, Egge A, Konglund AE, Ramm-Pettersen J, Dietrichs E, Taubøll E. Anterior thalamic deep brain stimulation in refractory epilepsy: A randomized, double-blinded study. Acta Neurol Scand. 2019 Mar;139(3):294-304. doi: 10.1111/ane.13047. Epub 2018 Dec 11. PMID: 30427061.

Hamdi H, Robin E, Stahl JP, Doche E, Azulay JP, Chabardes S, Bartolomei F, Regis J. Anterior Thalamic Stimulation Induced Relapsing Encephalitis. Stereotact Funct Neurosurg. 2019;97(2):132-136. doi: 10.1159/000499072. Epub 2019 May 3. PMID: 31055582.

Mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is a chronic neurological condition characterized by recurrent seizures (epilepsy) which originate in the temporal lobe of the brain with progressive neurological disabilities, including cognitive deficitanxiety and depression.

The seizures involve sensory changes, for example smelling an unusual odour that is not there, and disturbance of memory.

Mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) is the most common type of focal epilepsy.

see Temporal lobe epilepsy etiology.

In order to understand the pathophysiology of temporal lobe epilepsy (TLE), and thus to develop new pharmacological treatments, in vivo animal models that present features similar to those seen in TLE patients have been developed during the last four decades. Some of these models are based on the systemic administration of chemoconvulsants to induce an initial precipitating injury (status epilepticus) that is followed by the appearance of recurrent seizures originating from limbic structures.

Kainic acid and pilocarpine models, have been widely employed in basic epilepsy research. Their behavioral, electroencephalographic and neuropathologic features and response of these models to antiepileptic drugs and the impact they might have in developing new treatments are explained in the work of Lévesque et al. 1).

The transition to the ictal stage is accompanied by increasing global synchronization and a more ordered spectral content of the signals, indicated by lower spectral entropy. The interictal connectivity imbalance (lower ipsilateral connectivity) is sustained during the seizure, irrespective of any appreciable imbalance in the spectral entropy of the mesial recordings 2).

Recurrent seizures (epilepsy) which originate in the temporal lobe of the brain with progressive neurological disabilities, including cognitive deficitanxiety and depression.

The seizures involve sensory changes, for example smelling an unusual odour that is not there, and disturbance of memory.

Olfactory function was significantly impaired in patients with MTLE compared with healthy controls in all domains, namely threshold, discrimination, and identification. In addition, the olfactory bulb volume was smaller in patients with olfactory dysfunction 3).

Earlier tachycardia for seizures originating from the right versus left hemisphere in a patient with bilateral mesial temporal lobe epilepsy 4).

A strong association of this ailment has been established with psychiatric comorbidities, primarily mood and anxiety disorders. The side of epileptogenic may contribute to depressive and anxiety symptoms; thus, in a study, Radaelli et al. performed a systematic review to evaluate the prevalence of depression in TLE in surgical patients. The literature search was performed using PubMed/MedlineWeb of Science, and PsycNet to gather data from inception until January 2019. The search strategy was related to TLE, depressive disorder, and anxiety. After reading full texts, 14 articles meeting the inclusion criteria were screened. The main method utilized for psychiatric diagnosis was Diagnostic and Statistical Manual of Structured Clinical Interview for DSM Disorders. However, most studies failed to perform the neuropsychological evaluation. For those with lateralization of epilepsy, focus mostly occurred in the left hemisphere. For individual depressive diagnosis, 9 studies were evaluated, and 5 for anxiety. Therefore, from the data analyzed in both situations, no diagnosis was representative in preoperative and postoperative cases. In order to estimate the efficacy of surgery in the psychiatry episodes and its relation to seizure control, the risk of depression and anxiety symptoms in epileptic patients need to be determined before surgical procedures. Rigorous preoperative and postoperative evaluation is essential for psychiatry conditions in patients with refractory epilepsy candidates for surgery 5).

pilot study demonstrates that seizures in mesial temporal and temporal-plus epilepsies (i.e., temporoperisylvian) can be detected reliably in the anterior thalamic nucleus (ATN). Further studies are needed to validate these findings 6).

Fractional anisotropy asymmetry (FAA) values can be potentially used to identify the seizures of origin of TLE and to help understand the relationship between fiber tracts with the side of seizure origin of TLE 7).

The area of predominant perifocal 18F positron emission tomography hypometabolism and reduced [11C]flumazenil (11C-FMZ) -binding on PET scans is currently considered to contain the epileptogenic zone and corresponds anatomically to the area localizing epileptogenicity in patients with temporal lobe epilepsy (TLE).

Mesial temporal lobe epilepsy differential diagnosis.

Drug resistant epilepsy is a major clinical challenge affecting about 30% of temporal lobe epilepsy (TLE) patients.

The reasons for failure of surgical treatment for mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) remain unclear.

Mesial temporal lobe epilepsy treatment.

Temporal lobe epilepsy (TLE) is considered to be the most common form of epilepsy, and it has been seen that most patients are refractory to antiepileptic drugs.

After surgery for intractable mesiotemporal lobe epilepsy (mTLE) seizures recur in 30-40%. One predictor for seizure recurrence is the distribution of seizure onset and interictal epileptiform discharges (IED).

Preoperative bilateral ictal foci are a negative predictor for seizure outcome. Contrarily, IED exceeding the affected temporal lobe in the ipsilateral hemisphere or even bilateral IED had favorable seizure outcome if seizure onset is strictly limited to the affected temporal lobe. Reoperation for seizure persistence constitutes a promising therapeutic option 8).

The extent of pre-surgical perifocal PET abnormalities, the extent of their resection, and the extent of non-resected abnormalities were not useful predictors of individual freedom from seizures in patients with TLE 9).

see Mesial temporal lobe epilepsy case series.


Lévesque M, Avoli M, Bernard C. Animal Models of temporal Lobe Epilepsy Following Systemic Chemoconvulsant Administration. J Neurosci Methods. 2015 Mar 10. pii: S0165-0270(15)00091-6. doi: 10.1016/j.jneumeth.2015.03.009. [Epub ahead of print] PubMed PMID: 25769270.

Vega-Zelaya L, Pastor J, de Sola RG, Ortega GJ. Disrupted Ipsilateral Network Connectivity in Temporal Lobe Epilepsy. PLoS One. 2015 Oct 21;10(10):e0140859. doi: 10.1371/journal.pone.0140859. eCollection 2015. PubMed PMID: 26489091.

Türk BG, Metin B, Tekeli H, Sayman ÖA, Kızılkılıç O, Uzan M, Özkara Ç. Evaluation of olfactory and gustatory changes in patients with mesial temporal lobe epilepsy. Seizure. 2020 Jan 7;75:110-114. doi: 10.1016/j.seizure.2020.01.001. [Epub ahead of print] PubMed PMID: 31945715.

Yanai K, Shimada S, Kunii N, Takasago M, Takabatake K, Saito N. Earlier tachycardia for seizures originating from the right versus left hemisphere in a patient with bilateral mesial temporal lobe epilepsy [published online ahead of print, 2020 Jun 25]. Clin Neurophysiol. 2020;131(9):2168-2170. doi:10.1016/j.clinph.2020.06.011

Radaelli G, Majolo F, Leal-Conceição E, de Souza Santos F, Escobar V, Zanirati GG, Portuguez MW, Scorza FA, da Costa JC. Left Hemisphere Lateralization of Epileptic Focus Can Be More Frequent in Temporal Lobe Epilepsy Surgical Patients with No Consensus Associated with Depression Lateralization. Dev Neurosci. 2021 Mar 31:1-8. doi: 10.1159/000513537. Epub ahead of print. PMID: 33789300.

Pizarro D, Ilyas A, Toth E, Romeo A, Riley KO, Esteller R, Vlachos I, Pati S. Automated detection of mesial temporal and temporoperisylvian seizures in the anterior thalamic nucleus. Epilepsy Res. 2018 Jul 23;146:17-20. doi: 10.1016/j.eplepsyres.2018.07.014. [Epub ahead of print] PubMed PMID: 30055392.

Li H, Xue Z, Dulay MF Jr, Verma A, Karmonik C, Grossman RG, Wong ST. Fractional anisotropy asymmetry and the side of seizure origin for partial onset-temporal lobe epilepsy. Comput Med Imaging Graph. 2014 Jul 2. pii: S0895-6111(14)00102-5. doi: 10.1016/j.compmedimag.2014.06.009. [Epub ahead of print] PubMed PMID: 25037096.

Schmeiser B, Zentner J, Steinhoff BJ, Brandt A, Schulze-Bonhage A, Kogias E, Hammen T. The role of presurgical EEG parameters and of reoperation for seizure outcome in temporal lobe epilepsy. Seizure. 2017 Sep 6;51:174-179. doi: 10.1016/j.seizure.2017.08.015. [Epub ahead of print] PubMed PMID: 28888215.

Stanišić M, Coello C, Ivanović J, Egge A, Danfors T, Hald J, Heminghyt E, Mikkelsen MM, Krossnes BK, Pripp AH, Larsson PG. Seizure outcomes in relation to the extent of resection of the perifocal fluorodeoxyglucose and flumazenil PET abnormalities in anteromedial temporal lobectomy. Acta Neurochir (Wien). 2015 Sep 8. [Epub ahead of print] PubMed PMID: 26350516.

Corpus callosotomy

Corpus callosotomy

Because most of the corpus callosotomy (CC) series available in literature were published before the advent of vagus nerve stimulation (VNS), the efficacy of CC in patients with inadequate response to VNS remains unclear, especially in adult patients.

Corpus callosotomy is a palliative procedure especially for Lennox-Gastaut semiology without localization with drop attacks 1).

Palliative procedures such as corpus callosotomy (CC) and vagus nerve stimulation (VNS) may be effective for adequate seizure control in Lennox-Gastaut syndrome (LGS) patients who are not candidates for resective surgery.

No need to section anterior commissure. Can usually be performed via a bifrontal craniotomy utilizing a bicoronal skin incision.

Anterior corpus callosotomy.

Posterior callosotomy

The surgery is performed under general anesthesia. Electroencephalogram is not necessary, but if used, requires appropriate anesthetic agents that do not interfere with the recording. Mannitol, decadron, and prophylactic antibiotics are administered intravenously. The patient is placed supine on the table with the head turned toward the nondominant hemisphere, a shoulder roll under the contralateral shoulder and the vertex elevated by 30 to 45 degrees.

This position permits a minimum of retraction, as the dependent hemisphere is retracted by gravity and the operating microscope retains stereoscopic vision in the horizontal plane. A partial bicoronal incision is made 2 cm in front of the coronal suture, of sufficient length to permit the craniotomy, which extends 4 cm in front of, and 2 cm behind, the coronal suture and from 1 cm over the sagittal suture to the temporal insertion of the dependent side of the cranium.

Reviewing the angiogram from the Wada test or obtaining a Magnetic Resonance Venogram (MRV) may be helpful in surgical planning but it is usually possible to work around any draining veins. The dura is reflected over the sinus and the interhemispheric dissection is performed using the surgical microscope.

If gravity alone does not supply sufficient retraction, additional force can be attained either with two rolled up cotton paddies or gentle pressure from a self-retaining retractor. The glistening white corpus callosum is identified and exposed along its length, as are the two pericallosal arteries. Division of the corpus callosum is best performed under the operating microscope by dividing a small portion of the callosum and identifying the midline cleft between the ventricles where the septum pellucidum inserts. The use of frameless stereotaxy can be helpful in distinguishing the callosum from the cingulate gyri and defining the depth of the callosum, depending on the degree of brain shift. Without entering the ventricle, this cleft is followed first anteriorly around the genu and down to the rostrum. Additional posterior division can be performed with the help of frameless stereotaxy to achieve a 2/3 division. Alternatively, a metal clip can be placed at the back of the callosal division and a lateral radiograph obtained to ensure that the callo-sotomy has been carried out behind the line bisecting the glabella-inion line. A final metal clip is then placed at the posterior margin of the callosotomy to demarcate the limits of the resection in case a second operation is required to complete the callosotomy. Anticonvulsants are continued postoperatively.

Avoiding entry into the lateral ventricles

The anatomical basis for the technique is the presence of a definable cleft just ventral to the corpus callosum in the midline, formed by the fusion of the two laminae of the septum pellucidum. This small cleft is typically present even in the absence of a cavum septum pellucidum on MR imaging. The authors have found that dividing the body of the corpus callosum by exploiting the cleft of the septum pellucidum in the absolute midline is a simple and expeditious way to perform a callosotomy without entering the lateral ventricles 2). Traditionally corpus callosotomy is done through a craniotomy centered at the coronal suture, with the aid of a microscope. This involves dissecting through the interhemispheric fissure below the falx to reach the corpus callosum.

see interhemispheric approach.

It is performed between each pericallosal artery.

Neuronavigation facilitates orientation. The callosal body is transected through to the roof of the ipsilateral ventricle using an ultrasonic aspirator; the genu and rostrum are then identified and also split. If a total callosotomy is performed, transection of the splenium is performed with care given to preserve the crus of the fornix.

Meticulous microsurgical technique and knowledge of the limbic system’s anatomy is essential to keeping this procedure safe and effective 3).

Some advocate sectioning the CC with intraoperative EEG until the typical bisynchronous discharges that are usually seen become asynchronous 4).

Sood et al., describe a posterior interhemispheric approach to complete corpus callosotomy with an endoscope, which bypasses the need to perform interhemispheric dissection because the falx is generally close to the corpus callosum in this region 5).

Minimally invasive methods, such as MRI-guided laser interstitial thermal ablation (MTLA), are being employed to functionally remove or ablate seizure foci in the treatment of epilepsy. This therapy can achieve effectiveness similar to that of traditional resection, but with reduced morbidity compared with open surgery. Ho et al present a patient with a history of prior partial corpus callosotomy who continued to suffer from medically refractory epilepsy with bisynchronous onset. They report on the utilization of laser ablation of the splenium in this patient to achieve full corpus callosotomy. Adequate ablation of the splenial remnant was confirmed by postoperative MRI imaging, and at four-month follow-up, the patient’s seizure frequency had dropped more than 50%. This is the first reported instance of laser ablation of the splenium to achieve full corpus callosotomy following a previous unsuccessful anterior callosotomy in a patient with intractable generalized epilepsy 6).

As the corpus callosum is critical to the interhemispheric spread of epileptic activity, the procedure seeks to eliminate this pathway.

Sectioning of the corpus callosum interrupts generalized epileptiform discharges (as documented by the postoperative EEG) and usually results in a significant decrease in generalized seizure7).

Generalized seizure.

A complete CC should be considered as the initial procedure in lower-functioning children afflicted by absence, atonic seizure, or myoclonic seizures. Severely affected higher-functioning children may also benefit from a complete CC, without clinically significant disconnection syndromes. A completion posterior CC may benefit patients in whom a prior anterior CC has failed 8).

Sixty-five patients with lesions affecting the third ventricle (54 patients) or the corpus callosum itself (11 patients) underwent partial callosotomy or a circumscribed callosal resection. Before the surgery 20 patients were studied using the battery of cognitive, affective and behavioural tests which was repeated 10 and 100 days after surgery. No disconnection syndrome was over observed after the partial commissurotomy. Transcranial magnetic stimulation over the sensorimotor cortex was performed in 10 patients to determine conduction time of callosal fibres by measuring inhibition of tonic voluntary electromyographic activity in muscle’s ipsilateral to the activated hemisphere. It was found that this inhibition was absent in patients with lesions of the trunk of the corpus callosum and present in patients with lesions of the genu or splenium. In addition magnetic resonance imaging measurements of the corpus callosum were performed in 40 normal subjects to establish a classification system for corpus callosal area. The results showed a wide variability of the cross-sectional area of the corpus callosum. The comparison of the shape of the corpus callosum lead to a categorisation according to the presence and location of depressions on its surface 9).

Corpus callosotomy (CC) is a valuable palliative surgical option for children with medically refractory epilepsy due to generalized seizure or multifocal cortical seizure onset.

Single-stage upfront complete callosotomy is effective in relieving a broader spectrum of seizure types than anterior two thirds callosotomy or 2-stage complete callosotomy in children. The advantages of single-stage complete callosotomy must be weighed against the potentially higher risk of neurological and operative complications 10).

Incomplete section of the corpus callosum should be carefully evaluated as a cause of surgical failure 11).

Sagittal MRI cuts are ideal for assesing extent of division of the CC. Six individuals who had complete cerebral commissurotomy for medically intractable epilepsy participated in a magnetic resonance imaging study 20 or more years postoperatively. In all cases the completeness of callosotomy was clearly demonstrable. The status of the anterior commissure, cut in all six, could not be confirmed with the same confidence 12).

In all cortical areas, there were numerous atypical, supragranular pyramidal neurons with elongated “tap root” basilar dendrites. These atypical cells could be associated with an underlying epileptic condition and/or could represent a compensatory mechanism in response to deafferentation after callosotomy 13).

In 36 patients with drug-resistant epilepsy submitted to anterior callosotomy (27 cases), to two-stage total callosotomy (8 cases) and to posterior callosotomy (1 case) the EEG variations concerning background activity, focal activity and sharp-waves (SW) bisynchronous activity were evaluated. EEG modifications observed after callosotomy are the following: background rhythm tends to be better organised as spectral analysis demonstrated, this finding usually coincide with reduction of bisynchronous discharges. It appears that improvement in background activity cannot be correlated with outcome, but it seems to be to some extent since at the same time cognitive functions also seem to improve; however, this last aspect need to be checked in much larger series. The number and location of EEG foci do not change, but they appear to be more active; this is likely to depend only on the concomitant reduction of bisynchronous activity. No correlation seems to exist between the number and the location of foci, which are generally multiple. Lateralization of bisynchronous discharges as well as the reduction of their frequency and duration were observed. However, the clinical course is quite different: in some patients we have achieved good clinical responses in others postoperative results were poor. Lateralization of bisynchronous discharges is never absolute, on the grounds that in prolonged recordings bisynchronous discharges are nearly always present. Bisynchronous discharges in some cases are alternatively predominant in both hemispheres even within minutes or seconds. It was observed that after certain time, generally some months, lateralized discharges tend to generalize again, confirming that corpus callosum is replaced in discharge diffusion by other structures (brain-stem, diencephalon) 14).

Mild long-lasting neuropsychological deficits

Mutism and akinesia that usually resolves in weeks.

The effects of complete and partial corpus callosotomy in 6 patients were reported by Censori et al. Only the 2 cases undergoing total callosotomy showed evidence of impaired interhemispheric sensory transfer, related to sectioning of the splenium. Only mild long-lasting neuropsychological deficits were detected. Post-commissurotomy mutism and akinesia appeared in 4 cases, 2 with total, and 2 with partial anterior callosotomy. The short-and long-term effects of corpus callosotomy appear to be related to the extent of the section the creation of lesions during the surgical procedure, and a peculiar organization of cognitive functions in chronic epileptic patients 15).

Honda et al. retrospectively identified 106 patients who underwent CC for drug-resistant epilepsy before the age of 6 years, at the Nagasaki Medical Center, between July 2002 and July 2016. Patients’ developmental outcomes were evaluated one year after CC using the Kinder Infant Development Scale.

Results: The mean preoperative developmental quotient (DQ) was 25.0 (standard deviation [SD], 20.8), and the mean difference between preoperative DQ and one-year postoperative DQ was -1.6 points (SD, 11.6). However, 42.5% of patients had a mean DQ increase of 6.5 points (SD, 6.4), one year after CC from that before surgery. Factors related to the improvement in postoperative DQ were ‘low preoperative DQ’, ‘developmental gain 1 month postoperatively, and ‘postoperative seizure-free state’. Approximately 21.7% of patients were seizure-free 1 year after CC.

Performing CC, in infancy and early childhood for patients with drug-resistant epilepsy and severe developmental impairment, was associated with improved development in 42.5% of patients. Remission of seizures, even if only for a short period, contributed to the developmental improvement. From a developmental perspective, CC for drug-resistant epilepsy in early childhood is an effective treatment 16)

A 21-year-old female with medically refractory drop attacks that began at the age of 8 years, which resulted in the patient being progressively unresponsive to vagus nerve stimulation implanted at the age of 14 years. Corpus callosotomy was recommended to reduce the number of drop attacks. However, the patient had only mild cognitive impairments and no neurological deficits. For this reason, we were forced to plan a surgical approach able to maximize the disconnection for good seizure control while, at the same time, minimizing sequelae from disconnection syndromes and neurosurgical complications because in such cases of long-lasting epilepsy the gyri cinguli and the arteries can be tenaciously adherent and dislocated with all the normal anatomy altered. In this scenario, we opted for a microsurgical endoscopy-assisted anterior two-thirds corpus callosotomy. The endoscopic minimally invasive approach proved to be quite adequate in this technically demanding case and confirmed that CC may offer advantages, with good results, even in adult patients with drop attacks who have had inadequate response to VNS 17).


Englot DJ, Birk H, Chang EF. Seizure outcomes in nonresective epilepsy surgery: an update. Neurosurg Rev. 2016 May 21. [Epub ahead of print] Review. PubMed PMID: 27206422.

Joseph JR, Viswanathan A, Yoshor D. Extraventricular corpus callosotomy. J Neurosurg. 2011 Jun;114(6):1698-700. doi: 10.3171/2011.1.JNS101305. Epub 2011 Feb 18. PubMed PMID: 21332292.

Schaller K, Cabrilo I. Corpus callosotomy. Acta Neurochir (Wien). 2015 Nov 9. [Epub ahead of print] PubMed PMID: 26553285.

Epilepsy and the Corpus Callosum Softcover reprint of the original 1st ed. 1985 Edition by Alexander G. Reeves (Editor

Sood S, Asano E, Altinok D, Luat A. Endoscopic posterior interhemispheric complete corpus callosotomy. J Neurosurg Pediatr. 2016 Dec;25(6):689-692. PubMed PMID: 27611896.

Ho AL, Miller KJ, Cartmell S, Inoyama K, Fisher RS, Halpern CH. Stereotactic laser ablation of the splenium for intractable epilepsy. Epilepsy Behav Case Rep. 2016 Jan 13;5:23-6. doi: 10.1016/j.ebcr.2015.12.003. eCollection 2016. PubMed PMID: 26955518; PubMed Central PMCID: PMC4761694.

Gates JR, Leppik IE, Yap J, Gumnit RJ. Corpus callosotomy: clinical and electroencephalographic effects. Epilepsia. 1984 Jun;25(3):308-16. PubMed PMID: 6723592.

Jalilian L, Limbrick DD, Steger-May K, Johnston J, Powers AK, Smyth MD. Complete versus anterior two-thirds corpus callosotomy in children: analysis of outcome. J Neurosurg Pediatr. 2010 Sep;6(3):257-66. doi: 10.3171/2010.5.PEDS1029. PubMed PMID: 20809710.

Woiciechowsky C, Vogel S, Meyer BU, Lehmann R. Neuropsychological and neurophysiological consequences of partial callosotomy. J Neurosurg Sci. 1997 Mar;41(1):75-80. PubMed PMID: 9273862.

Kasasbeh AS, Smyth MD, Steger-May K, Jalilian L, Bertrand M, Limbrick DD. Outcomes after anterior or complete corpus callosotomy in children. Neurosurgery. 2014 Jan;74(1):17-28. doi: 10.1227/NEU.0000000000000197. PubMed PMID: 24089047.

Shimizu H. Our experience with pediatric epilepsy surgery focusing on corpus callosotomy and hemispherotomy. Epilepsia. 2005;46 Suppl 1:30-1. PubMed PMID: 15816976.

Bogen JE, Schultz DH, Vogel PJ. Completeness of callosotomy shown by magnetic resonance imaging in the long term. Arch Neurol. 1988 Nov;45(11):1203-5. PubMed PMID: 3190501.

Jacobs B, Creswell J, Britt JP, Ford KL, Bogen JE, Zaidel E. Quantitative analysis of cortical pyramidal neurons after corpus callosotomy. Ann Neurol. 2003 Jul;54(1):126-30. PubMed PMID: 12838530.

Quattrini A, Papo I, Cesarano R, Fioravanti P, Paggi A, Ortenzi A, Foschi N, Rychlicki F, Del Pesce M, Pistoli E, Marinelli M. EEG Patterns after callosotomy. J Neurosurg Sci. 1997 Mar;41(1):85-92. PubMed PMID: 9273864.

Censori B, Del Pesce M, Provinciali L, Quattrini A, Mancini S, Papo I. Functions of the corpus callosum: observations from callosotomy performed for intractable epilepsy. Boll Soc Ital Biol Sper. 1989 Jan;65(1):53-9. PubMed PMID: 2757819.

Honda R, Baba H, Adachi K, Koshimoto R, Ono T, Toda K, Tanaka S, Baba S, Yamasaki K, Yatsuhashi H. Developmental outcome after corpus callosotomy for infants and young children with drug-resistant epilepsy. Epilepsy Behav. 2021 Feb 17;117:107799. doi: 10.1016/j.yebeh.2021.107799. Epub ahead of print. PMID: 33610103.

Nasi D, Iacoangeli M, Di Somma L, Dobran M, Di Rienzo A, Gladi M, Benigni R, Passamonti C, Zamponi N, Scerrati M. Microsurgical endoscopy-assisted anterior corpus callosotomy for drug-resistant epilepsy in an adult unresponsive to vagus nerve stimulation. Epilepsy Behav Case Rep. 2016 Jan 20;5:27-30. doi: 10.1016/j.ebcr.2016.01.001. eCollection 2016. PubMed PMID: 26955519; PubMed Central PMCID: PMC4761696.
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