Abstract
Selective Posterior Callosotomy for Drop Attacks: A New Approach Sparing Prefrontal Connectivity
Paglioli E, Martins WA, Azambuja N, Portuguez M, Frigeri TM, Pinos L, Saute R, Salles C, Hoefel JR, Soder RB, da Costa JC, Hemb M, Theys T, Palmini A. Neurology 2016;87(19):1968–1974.
OBJECTIVE: To evaluate a novel approach to control epileptic drop attacks through a selective posterior callosotomy, sparing all prefrontal interconnectivity. METHODS: Thirty-six patients with refractory drop attacks had selective posterior callosotomy and prospective follow-up for >4 years. Falls, episodes of aggressive behavior, and IQ were quantified. Autonomy in activities of daily living, axial tonus, and speech generated a functional score ranging from 0 to 13. Subjective effect on patient well-being and caregiver burden was also assessed. RESULTS: Median monthly frequency of drop attacks decreased from 150 to 0.5. Thirty patients (83%) achieved either complete or >90% control of the falls. Need for constant supervision decreased from 90% to 36% of patients. All had estimated IQ below 85. Median functional score increased from 7 to 10 (p = 0.03). No patient had decrease in speech fluency or hemiparesis. Caregivers rated the effect of the procedure as excellent in 40% and as having greatly improved functioning in another 50%. Clinical, EEG, imaging, and cognitive variables did not correlate with outcome. CONCLUSIONS: This cohort study with objective outcome assessment suggests that selective posterior callosotomy is safe and effective to control drop attacks, with functional and behavioral gains in patients with intellectual disability. Results are comparable to historical series of total callosotomy and suggest that anterior callosal fibers may be spared. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that selective posterior callosotomy reduces falls in patients with epileptic drop attacks.
Commentary
Composed of approximately 180 million axons, the corpus callosum is the most prominent interhemispheric commissure. It connects associative cortical regions and is crucial for integrating numerous processes between the two hemispheres. The posterior third of the corpus callosum is probably larger in men with dyslexia (1), although there is no agreement about consistent correlation between the morphology and function of the callosum. With the exception of some tractography studies, most correlations between fiber loss and neurologic disorders have been based on postmortem studies (2).
In the 1940s, it was reported that disconnection of the corpus callosum in monkeys prevented spread of ictal discharges and seizure generalization. Additionally, it was observed that patients with epilepsy who had a stroke involving the corpus callosum experienced subsequent amelioration of seizures. Gradually, the procedure was introduced to clinical practice, and Wilson et al. (3) reported a 9-year-old boy with as many as 30 generalized seizures a day who became seizure free, on no anticonvulsant medications, after a complete commissurotomy. Currently, the most common indication for callosotomy at most comprehensive epilepsy centers is in patients with injurious tonic, atonic, or drop attack seizures.
Like most surgical procedures, the technique of callosotomy evolved over the years. Initially, complete sectioning of the callosum was done, but eventually the sectioning became limited to the anterior callosal fibers. Focusing on the anterior fibers was based on the premise that severing the connections in the motor system is most effective in reducing drop attacks. In patients who do not experience better seizure control, however, a repeat procedure to section the posterior fibers is often recommended. Therefore, the posterior resection appears to be more effective in reducing seizures (4).
Paglioli et al. (5) realized that the motor fibers cross more posteriorly than initially thought and performed selective posterior callosotomy sparing prefrontal connectivity in 36 subjects. These subjects had a mean duration of epilepsy of 18.1 years (±11.6 years) and age at surgery 21.5 years (±11.3 years). The authors followed these subjects prospectively for at least 5 years. Median drop attacks decreased from 150 to 0.5 per month, with 30 subjects (83%) achieving 90 to 100 percent reduction of attacks. Only 6 patients (17%) did not appear to benefit significantly from the procedure. The patients achieved a higher degree of independence; only 36% of them needed continuous supervision after the callosotomy compared with 90% before surgery.
The procedure resulted in no significant dyspraxia, akinetic mutism, speech decline, or hemiparesis. Five patients (14%) exhibited paroxysms of aggression at a frequency of at least once a week after the procedure compared with 16 patients (44%) preoperatively. As regards the subjective reports of caregivers, the result was considered excellent in 40% of patients, great functional improvement was reported in 50%, and only one subject was judged as worsened.
These results are comparable with those of complete callosotomy, confirming the authors’ observations that motor fibers cross in the middle and posterior thirds of the corpus callosum and explaining why anterior callosotomy sometimes fails in controlling drop attacks. Indeed, diffusion magnetic resonance imaging tractography was done to generate a map of the corpus callosum (2). The authors found that fibers from motor cortices traveled around and posterior to the isthmus of the corpus callosum all the way to the borders of the splenium. It is likely that this study will lead to more surgical series adopting the same technique. Future studies should assess preoperative and postoperative seizure frequency more accurately, perhaps by continuous/ambulatory video EEG monitoring or by other modern devices, such as a validated seizure detection watch. Additionally, future studies should implement more detailed neuropsychological assessments aiming to highlight the importance of preserving the prefrontal interhemisheric connections.