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Summary: Purpose: To describe seizure control, complications, adaptive function and language skills following hemispheric surgery for epilepsy.
Methods: Retrospective chart review of patients who underwent hemispheric surgery from July 1993 to June 2004 with a minimum follow-up of 12 months.
Results: The study population comprised 24 children, median age at seizure onset six months and median age at surgery 41 months. Etiology included malformations of cortical development (7), infarction (7), Sturge-Weber Syndrome (6), and Rasmussen's encephalitis (4). The most frequent complication was intraoperative bleeding (17 transfused). Age <2 yr, weight <11 kg, and hemidecortication were risk factors for transfusion. Postoperative complications included aseptic meningitis (6), and hydrocephalus (3). At median follow-up of 7 yr, 79% of patients are seizure free. Children with malformations of cortical development and Rasmussen's encephalitis were more likely to have ongoing seizures. Overall adaptive function scores were low, but relative strengths in verbal abilities were observed. Shorter duration of epilepsy prior to surgery was related significantly to better adaptive functioning.
Conclusions: Hemispheric surgery is an effective therapy for refractory epilepsy in children. The most common complication was bleeding. Duration of epilepsy prior to surgery is an important factor in determining adaptive outcome.
Hemispheric surgery is an established treatment for medically refractory epilepsy due to diffuse hemispheric disease. Krynauw (1950) reported the first series of 12 patients with infantile hemiplegia who underwent anatomic hemispherectomy for hemispheric disease and epilepsy. In 1961, White, in a review of the literature on hemispherectomy for infantile hemiplegia, reported 6.6% postoperative mortality in a total of 267 patients. In the 1960s, concerns about late complications of anatomic hemispherectomy were raised. Oppenheimer and Griffith (1966) described three of 17 patients with recurrent episodes of encephalopathy, obstructive hydrocephalus and superficial cerebral hemosiderosis 3–11 yr following hemispherectomy leading to death. Rasmussen (1983) also described intracranial hypertension due to hydrocephalus in 11 of 31 patients, 4.5–24 yr following surgery. He attributed this to the extent of resection of the hemisphere and its coverings. To reduce complications, changes in surgical technique have evolved to include subtotal resection, functional hemispherectomy, and hemidecortication (Carson et al., 1996).
Villemure and Mascott in 1995 described ‘peri-insular hemispherotomy’ which, in their hands, resulted in shorter operative times and fewer early postoperative complications and bleeding. Seizure control was comparable to anatomic hemispherectomy but morbidity and mortality rates were lower (Villemure and Mascott, 1995; Kestle et al., 2000). There have been numerous reports on the outcomes following hemispheric surgery in children with medically refractory epilepsy (Carson et al., 1996; Vining et al., 1997; Battaglia et al., 1999; Boatman et al., 1999; Carreno et al., 2001; Kossoff et al., 2002; Devlin et al., 2003; Daniel and Villemure, 2003; Kossoff et al., 2003; van Empelen et al., 2004; Jonas et al., 2004; Piastra et al., 2004; Pulsifer et al., 2004; Gonzalez-Martinez et al., 2005; Shimizu, 2005). These studies have examined either aspects of cognitive, behavioral and motor outcomes, seizure control or postoperative complications in terms of etiology and outcome predictors. However, there is limited published data reporting both medical and surgical morbidity in a continuous series, which highlights all risk factors and details outcomes.
The objective of this study is to report on seizure control, morbidity, language skills and adaptive functions in a consecutive series of children who underwent hemispheric surgery at our center over an 11 year period and to identify specific risk factors affecting surgical, medical and functional outcomes.
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Although this is a relatively small series of patients, no children were lost to follow-up. In previously reported series, there was either lack of or shorter follow-up periods of all patients (Devlin et al., 2003; Kossoff et al., 2003; van Empelen et al., 2004; Jonas et al., 2004). In this series, 83% of patients had onset of epilepsy in the first year of life, similar to other reports (Devlin et al., 2003; Jonas et al., 2004; Gonzalez-Martinez et al., 2005). Neonatal onset epilepsy and West syndrome were common, 42% of patients.
Complete seizure control in 79% compares favorably with published data. Krynauw (1950) reported complete seizure control in all but one patient, and 67% of patients were seizure free in White's (1961) review of anatomic hemispherectomy. Following functional hemispherectomy, seizure-free outcomes have ranged from 52 to 75% (Devlin et al., 2003; van Empelen et al., 2004; Jonas et al., 2004; Shimizu, 2005; Gonzalez-Martinez et al., 2005). Patients with epilepsy due to acquired vascular pathologies appear to have the best outcome, and malformations of cortical development, especially hemimegalencephaly, are associated with the worst outcome (Devlin et al., 2003; Kossoff et al., 2003; Jonas et al., 2004; Gonzalez-Martinez et al., 2005; Shimizu, 2005). Van Empelen et al. (2004), reported a less favorable seizure outcome in patients with Rasmussen's encephalitis. However, in the various series in the literature, there are differences in etiology, which may have influenced seizure outcome. Cerebral infarction and Sturge-Weber syndrome were more common in our series than in the series reported by Devlin et al. (2003) and Jonas et al. (2004) where malformations of cortical developmental were the most common. Rasmussen's encephalitis was more common in the reports of Kossoff et al. (2003) and Van Empelen et al. (2004).
In published series, blood loss and the requirement for blood transfusion are frequently encountered and expected complications of hemispheric surgery, and may be associated with hypovolemia and death (Devlin et al., 2003; Jonas et al., 2004; Piastra et al., 2004; Gonzalez-Martinez et al., 2005). In our series, there was a wide variation in blood loss. Hemidecortication, was associated with more severe bleeding requiring replacement. Young age and low weight were also important factors in predicting severe blood loss. Carson et al. (1996) and Vining et al. (1997) reported, in large series of patients who underwent hemidecortication, significant intraoperative bleeding and volume depletion in 12/58, most frequently seen in patients with malformations of cortical development (age less than 1 yr in all but one patient), followed by Rasmussen's encephalitis (older age group) and Sturge-Weber syndrome (where the only death related to bleeding occurred). Similarly, Piastra et al. (2004) noted that hemimegalencephaly was associated with greater risk of bleeding but this may be related to the younger age at surgery (less than 12 months). Kossoff et al. (2002) reported a series of 32 patients with Sturge-Weber syndrome undergoing hemispheric surgery, with four patients having significant intraoperative bleeding. Gonzalez-Martinez et al. (2005) reported no risk factors associated with degree of blood loss although the mean weight at surgery was 9.3 kg, all patients were less than 2 yr at time of surgery and all but one patient had abnormalities of cortical development. We report the first use of autologous blood in hemispheric surgery and in the patients where this technique was employed the use of allogenic blood was avoided. Other strategies employed to reduce transfusions and its complications included staging of the hemispheric surgery in very young patients and those of low body weight, and the use of rhEPO but this is not an approved indication for widespread use of rhEPO.
Hydrocephalus requiring the insertion of a shunt occurs less frequently with functional hemispherectomies than hemidecortication (Carson et al., 1996) and anatomic hemispherectomies (Rasmussen, 1983). However, it remains a risk of surgery, occurring in 9–11% of cases (Devlin et al., 2003; Gonzalez-Martinez et al., 2005; Shimizu, 2005). Hemimegalencephaly has been more frequently associated than other pathologies with the need for shunting posthemispheric surgery (Vining et al., 1997; Devlin et al., 2003; Shimizu, 2005).
In this series, two patients (8%) required reoperation because of incomplete disconnection for persistent seizures and are now seizure-free. Both had Rasmussen's encephalitis; one had a hemidecortication and the other peri-insular hemispherotomy. Gonzalez-Martinez et al. (2005) report reoperation for persistent seizures related to incomplete disconnection in three (16%). Symptomatic hyponatremia and SIADH (Jonas et al., 2004) has infrequently been reported as a postoperative complication despite the nature of the surgery and the young population. We encountered this problem in only one patient. The other complications observed in our patients were self-limiting, required no specific therapy, and had no long term consequences for the patients.
The expected postoperative motor impairment in our patients is comparable to that described in reports by Vining et al. (1997) and Devlin et al. (2003). However, we did not document improvement postoperatively in preexisting hemiplegia which has been previously reported (Krynauw, 1950; White, 1961; Devlin et al., 2003) although all patients continued to develop gross motor function or maintain ambulatory abilities. We observed worsening of preoperative hemiplegia in 17% of patients, which contrasts with White's (1961) report of only 6%. This may be explained in part by the younger age at surgery in our series at which time the full extent of the hemiplegia had not yet become apparent. Homonomous hemianopia is an expected complication following hemispheric surgery in all patients, as is loss of useful hand function.
Postoperative severe headache and chronic intracranial hypertension have been reported (Carson et al., 1996). Late intracranial hypertension occurred in one patient in our series, and was likely due to a disturbance of cerebrospinal fluid flow dynamics. This patient responded to acetazolamide and further surgery was not required. Migraine has not been previously reported following hemispheric surgery. The prevalence of migraine requiring prophylactic therapy observed in our study was 17%; most patients had malformations of cortical development and all had undergone periinsular hemispherotomy. A family history of migraine in a first degree relative was observed in all. Bigal et al. (2003) reviewed the relationship between epilepsy and migraine, and reported prevalence of 8–15% in the literature, with an increased incidence of migraine in both idiopathic and symptomatic epilepsy. Yankovsky et al. (2005) recently reported in a series of adults with intractable partial epilepsy undergoing presurgical evaluation a 59% incidence of recurrent headaches; migraine occurring in 27%. Yamane et al. (2004) reported a migraine rate of 20% in a study examining comorbidity of headaches and epilepsy in children. Gee et al. (2003) documented the prevalence of postcraniotomy headache in 19% of cases (11/58), eight of whom had craniotomy as part of surgical management of epilepsy (no hemispheric procedures were performed).
With respect to cognitive and adaptive functioning, the most striking finding was the relationship of duration of epilepsy to SIB-R scores, such that better outcome in terms of overall broad independence and functioning in all four SIB-R domains was associated with a shorter duration of epilepsy. This finding is similar to the results of Jonas et al. (2004), and suggests that prolonged seizure activity may be a risk factor for poor outcomes, possibly by adversely affecting the nonoperated hemisphere. Thus, as suggested by Jonas et al. (2004), early control of seizures, in this case via hemispheric surgery, should be a high priority. Devlin et al. (2003) also reported that duration of epilepsy prior to surgery negatively impacted on behavior in a subgroup of their patients, although details of the specific behavioral/adaptive measures were not described. A history of infantile spasms further negatively impacted functional outcome; impact on the contralateral ‘normal’ hemisphere may be a particular feature of this type of epileptic encephalopathy, or serve as a marker for global cognitive dysfunction.
Our data also suggest that younger age at surgery is a positive factor with respect to aspects of postsurgical adaptive functioning, with higher SIB-R Broad Independence and Social/Communication scores related to earlier age at surgery. This finding supports the claim made by Devlin et al. (2003) that younger age at surgery maximizes the beneficial effects of surgery on future development, suggesting greater developmental plasticity early in life. However, it is notable that this outcome was not uniform in our series; specifically, the three children with the earliest age at surgery in our sample had SIB-R Broad Independence scores in the very low range (<1st percentile). Thus, although it appears to be generally related to a better prognosis, younger age at surgery does not guarantee better adaptive functioning at follow-up. It is also important to note that children in this series, and in most series in the literature, are not randomly assigned to early vs. late surgical intervention. Thus, in many cases, age at surgery may be related to specific patient characteristics that lead to early surgical intervention such as seizure severity and etiology.
We observed a relative preservation of verbal abilities, both in terms of functional skills as assessed by the SIB-R, and in terms of standardized assessment via PPVT-III, after hemispheric surgery. Similar findings have been reported by Devlin et al. (2003) and Jonas et al. (2004). Language functioning, as indicated by the PPVT-III and SIB-R Social/Communication scores, was an area of strength overall in our sample at follow-up. A relative preservation of language abilities is well recognized in children following hemispherectomy, which is independent of laterality of disease (Krynauw, 1950; White, 1961). Mariotti et al. (1998) discussed the hypothesis of early hemisphere equipotentiality relating to linguistic abilities and that there may be a functional reorganization in a hierarchical fashion privileging linguistic skills. However, Vanlancker-Sidtis (2004) has reported a case where subtle deficiencies in higher linguistic function after hemispherectomy were demonstrated at follow-up, suggesting an incomplete equipotentiality of the hemispheres or a developmental or age limitation to full preservation of language skills. This is also supported by our findings. Although language was an area of relative strength, standard scores were nevertheless generally below age expectations in the majority of children.
Our study is limited by a relatively small sample size and lack of complete preoperative and serial postoperative adaptive functioning and cognitive data on all patients.