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.
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.
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).
Mechanism of action
As the corpus callosum is critical to the interhemispheric spread of epileptic activity, the procedure seeks to eliminate this pathway.
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).
EEG Patterns after callosotomy
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
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).