- Email: [email protected]
An observational study on outcome of hemispherotomy in children with refractory epilepsy
International Journal of Surgery xxx (2015) 1e6
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Original research
An observational study on outcome of hemispherotomy in children with refractory epilepsy Manas Panigrahi a, *, Shyam Sundar Krishnan a, Sudhindra Vooturi b, Rammohan Vadapalli c, Shanmukhi Somayajula b, Sita Jayalakshmi b a b c
Department of Neurosurgery, Krishna Institute of Medical Sciences, Minister Road, Secunderabad, 03 Telangana, India Department of Neurology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad, 03 Telangana, India Department of Radiology, Vijaya Diagnostic Centre, Hyderabad, India
h i g h l i g h t s Retrospective analysis of data in 21 children who underwent hemispherotomy. Gliosis was most common etiology, observed in 13 (62.0%) of the children. Improved QOLIE scores was observed in nearly 85% children at last follow-up. Hemispherotomy offers good outcome in psychosocial behaviors at follow up.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 1 April 2015 Received in revised form 15 May 2015 Accepted 29 May 2015 Available online xxx
Introduction: The current study aimed to evaluate the clinical characteristics and outcome of hemispherotomy in children with refractory hemispherical epilepsy. Methods: Retrospective analysis of data in twenty one children aged 12 years who underwent hemispherotomy and had at least two years post surgery follow-up was performed. Sixteen children underwent Delalande's vertical para-sagittal hemispherotomy (VPH), while lateral peri-insular functional hemispherotomy was performed in the rest. Results & discussion: The average age of onset for epilepsy in the study population was 2.9 ± 2.4 years; the average duration of epilepsy was 4.0 ± 2.9 years. The mean age at surgery of the study population was 6.8 ± 2.8 years. Six (28.5%) children were girls. Gliosis due to presumed childhood infarct was most common etiology, observed in 13 (62.0%) of the children, followed by Rasmussen's encephalitis in six (28.5%). There was no significant difference between the surgery groups for the reported acute post operative seizures (APOS) (20.0% vs. 25.0%; p ¼ 1.000). At last follow up 90.5% patients were seizure free; there was no difference between the groups for seizure freedom (60.0% vs. 87.5%; p ¼ 0.228). When analyzed for outcome between the etiologies, seizure freedom was similar for gliosis due to infarct (76.9%), Rassmussens encephalitis (83.3%) and malformations of cortical development (MCD) (100.0%). Moreover, improved quality of life in epilepsy (QOLIE) scores was observed in 80.0% of the lateral periinsular functional hemispherotomy group and 87.5% children in VPH group at the last follow-up. Conclusion: Gliosis due to presumed childhood infarct was the leading cause of medically refractory epilepsy caused by hemispheric lesions in the current study. Encouragingly, hemispherotomy offers seizure freedom (in 90.5% patients) and improvement in QOLIE scores at two years follow up. © 2015 Published by Elsevier Ltd on behalf of IJS Publishing Group Limited.
Keywords: Hemispherotomy Outcome in children Gliosis Refractory SE
1. Introduction
* Corresponding author. Krishna Institute of Medical Sciences, 1-8-31/1, Ministers Road, Secunderabad, Telangana 500003, India. E-mail address: [email protected] (M. Panigrahi).
Hemispherectomy is a proven treatment for medically refractory epilepsies due to congenital or acquired hemispheric or multilobar epileptogenic lesions with a current success rate of 50e80% [1e6]. Walter Dandy [7] in 1928 reported the use of
http://dx.doi.org/10.1016/j.ijsu.2015.05.049 1743-9191/© 2015 Published by Elsevier Ltd on behalf of IJS Publishing Group Limited.
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
2
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
cerebral hemispherectomy in patients with intractable unihemisphereic lesions. However, limited resections and disconnections were largely preferred by 1980s after complications of classic anatomical hemispherectomy like obstructive hydrocephalus, haemosiderosis and intracranial haematoma were reported in nearly 30% of the patients [8,9]. After the introduction of functional hemispherectomy by Rasmussen et al. [9], in 1974 the morbidity and mortality declined however at similar seizure outcome when compared to classic anatomic hemispherectomy [2,10e12]. Delalande et al. [12] later described less invasive technique of hemispherotomy for which variations were subsequently proposed [13]. This evolution progressed to more recent techniques like, vertical para-sagittal hemispherotomy and Peri -insular hemispherotomy in efforts to reduce morbidity while preserving efficacy [1e4]. When comparing various surgical techniques, existing literature indicates that hemispherotomy is associated with fewer complications than functional hemispherectomy [14]. When compared for the seizure outcome between the groups, while few studies have reported non-significant difference between functional hemispherectomy and hemispherotomy [15], multi center trials with large series have reported significantly more number of patients undergoing hemispherotomy as seizure-free as the functional hemispherectomy groups. Encouragingly, an increasing number of studies show that hemispherotomy is associated with improvements in post-operative development, quality of life (QOL) and adaptive behaviors in children by reducing the seizure frequency [16e18]. Disparities in aetiology have been reported in developing countries and even within a given developing country [19]. Major differences between developing and developed world exist in access to and availability of epilepsy management programs, which are very limited in developing world [20]. Implementing surgical strategies in developing countries in a large scale is very essential given the fact that epilepsy surgeries like anterior temporal lobectomy has been proved to be more feasible and cost-effective than medical management of refractory status epilepticus in developing countries [21]. However, very limited literature exists on the role of hemispherotomy in developing countries where the probability of medically refractory hemispherical epilepsy patient being young, fully contributing members of society is higher. Therefore, fewer the complication the more desirable is the surgical intervention.
seizures, history of neonatal seizures, febrile convulsions, status epilepticus and clinical findings of neurological examination. In children aged above 2 years, developmental quotient (DQ), social quotient (SQ), and intelligence quotient (IQ) were assessed using standardized tests like developmental screening test, vineland social maturity scale, Binet-Kamath Intelligence Scale, Furthermore, quality of life (QOL) was assessed using quality of life in epilepsy (QOLIE 48) where a score of more than fifty of a maximum of hundred points was considered as good outcome. A parental interview was done to evaluate further about child's behavior, cognitive abilities, physical and neurological disability. Montreal handedness test, behavioral problem assessment, and psychiatric evaluation according to international classification of diseases (ICD10) were performed. Imaging of brain was done with 1.5 T MRI in six and 3 T MRI in the remaining children. Functional MRI for language mapping was done in two and for motor mapping in six children. All the children underwent pre and post surgery diffusion tensor imaging (DTI) with tractography. All the children underwent prolonged videoEEG (VEEG) monitoring. Ictal single photon emission computed tomography (SPECT) was performed in ten children, eight children underwent interictal fluoro deoxy-D-glucose positron emission tomography (FDG PET). Interictal spikes were grouped as unilateral (>75% on the ipsilateral side of the imaging abnormality) and multifocal.
1.1. Aim
2.4. Statistical analysis
The current study aimed to evaluate the clinical characteristics and outcome of functional hemispherotomy in Indian children with medically refractory hemispherical epilepsy syndromes.
All continuous variables are expressed as mean ± SD. All the categorical variables are expressed as frequencies and percentages. The distribution of the study variables and outcome of the entire study population is depicted using frequency distribution charts. All the study variables were compared between the two types of surgeries; where paired student t-test was used to compare for continuous variables before and after the surgery and unpaired student t-test was used to compare continuous variables between the surgery groups. Chi-square test was used to compare between the surgeries for categorical variables. A p value of 0.05 was considered significant. Statistical analysis was done using Statistical Software for Social Sciences (SPSS, version 17.0 IBM Computers, NewYork, USA).
2. Materials & methods Retrospective analysis of data of twenty two children aged 12 years and below, who underwent hemispherotomy at Krishna Institute of Medical Sciences, a tertiary referral care centre in South India was done. All the children had at least two years post surgery follow-up. The presurgical, surgical and post-surgical variables were included in the data analysis. One child died at day 10 of the hospital stay and was subsequently excluded from analysis of long term outcome. The study was approved after review by the institutional ethics committee. 2.1. Pre surgical evaluation The clinical evaluation included variables such as age at surgery, gender, aetiology, age of onset of epilepsy, type and frequency of
2.2. Surgery Sixteen children underwent Delalande's vertical para-sagittal Hemispherotomy (VPH) while lateral peri insular functional hemispherectomy was performed in five children. 2.3. Post surgical evaluation and outcome The post-operative hospital course, complications, and functional outcome data were collected and analyzed. Acute postoperative seizures (APOS) were defined as seizures occurring within 7 days after surgery. All the patients were assessed for IQ, development, and behavioral problems and quality of life at three months and one year post surgery. The outcome at the last follow up was assessed using to the Engel's outcome classification where Engel's class I was considered seizure free [22].
3. Results In the current study on 21 children who underwent hemispherotomy at our center and followed up for a mean 25.4 ± 1.5 months post surgery, the average age of onset of epilepsy was 2.9 ± 2.4 years; the average duration of epilepsy was 4.0 ± 2.9 years.
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
3
Table 1 Comparison between surgical approaches for clinical and demographic variables. S.No
Variable
Lateral peri insular functional hemispherotomy (n ¼ 5)
Vertical para-sagittal hemispherotomy (n ¼ 16)
p value
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Female (%) Age (years) Age of onset (years) Neonatal onset of seizures (%) Duration of epilepsy Febrile convulsions (%) Childhood insult (%) Multiple types of seizures (%) Low IQ of <75 (%) Good quality of life (%) Psychiatric co-morbidities (%) Developmental delay (%) History of status epilepticus (%) Family history of epilepsy (%) Daily Seizures (%) Hemiparesis (%)
0 (0.0%) 8.0 ± 2.9 3.2 ± 2.3 1 (20.0%) 4.6 ± 2.0 1 (20.0%) 1 (20.0%) 3 (21.4%) 5 (100.0%) 0 (0.0%) 0 (0.0%) 4 (80.0%) 3 (60.0%) 0 (0.0%) 5 (100.0%) 4 (80.0%)
6(37.5%) 6.5 ± 2.7 2.9 ± 2.5 2 (12.5%) 3.8 ± 3.2 2 (12.5%) 6 (37.5%) 11 (78.6%) 13 (81.3%) 1 (6.3%) 12 (80.0%) 9 (56.3%) 5 (31.3%) 4 (25.0%) 14 (87.5%) 15 (93.8%)
0.262 0.303 0.829 1.000 0.636 1.000 0.624 1.000 0.549 1.000 0.004 0.606 0.325 0.532 1.000 0.429
Table 2 Comparison between surgical approaches for etiology (n ¼ 21). Lateral peri insular functional hemispherotomy (n ¼ 5) Vertical para-sagittal hemispherotomy (n ¼ 16) p value
S.No Variable 1 2 3 4 5 6 7
Gliosis due to presumed childhood infarct (%) 3 (60.0%) Rasmussen's encephalitis (%) 1 (20.0%) Hemispherical malformation (%) 1 (20.0%) Acute post operative seizures(%) 1 (20.0%) Interi-ictal EEG concordant (%) 2 (40.0%) Multiple types of seizures (%) 5 (100.0%) Ictal EEG concordant(%) 2 (40.0%)
10 5 1 4 9 6 11
(62.5%) (31.3%) (6.3%) (25.0%) (56.3%) (37.5%) (68.8%)
1.000 1.000 0.428 1.000 0.635 0.035 0.325
Table 3 Comparison between surgical approaches types for outcome (n ¼ 21). S.No
Variable
Lateral peri insular functional hemispherotomy (n ¼ 5)
Vertical para-sagittal hemispherotomy (n ¼ 16)
p value
1 2 3 4 5
Seizure free at last follow up (%) Improved cognition (%) Back to school (%) Good long term QOLIE (%) Improved psychological score (%)
4 4 2 4 5
15 12 8 14 15
0.429 1.000 1.000 1.000 1.000
(80.0%) (80.0%) (40.0%) (80.0%) (100.0%)
The mean age at surgery of the study population was 6.8 ± 2.8 years with six (28.5%) female patients. While five (23.8%) children underwent lateral peri insular functional hemispherotomy, the remaining 16 (76.2%) patients underwent VPH. At last follow up 19 children were seizure free. While 11 (52.3%) children were off antiepileptic drugs (AEDs), rest of the children needed fewer than half the original number of AEDs. Encouragingly, 16 (76.2%) children reported improved cognitive function and 20 (95.2%) children scored better in psychological tests. 3.1. Demographic and clinical variables There were no significant differences between the groups for number of women (0.0% vs. 37.5%; p ¼ 0.262), age of onset of epilepsy (3.2 ± 2.3 vs. 2.9 ± 2.5; p ¼ 0.829) and age at surgery (8.0 ± 2.9 vs. 6.5 ± 2.7; p ¼ 0.303). Family history of epilepsy (0.0% vs. 25%; p ¼ 0.532) and history of childhood insult (20.0% vs. 37.5%; p ¼ 0.624) was similar among both the groups. Moreover, both the groups did not differ for children with multiple types of seizures (60.0% vs. 78.6%; p ¼ 1.000) and children who reported daily seizures (100.0% vs. 87.5%; p ¼ 1.000), Table 1. Distribution of etiologies of Rasmussen's encephalitis (20.0% vs. 31.3%; p ¼ 1.000), gliosis due to presumed childhood infarct (60.0% vs. 62.5%; p ¼ 1.000) and malformations of cortical development (MCD) (20.0% vs. 6.3%; p ¼ 0.428) was similar between both the groups.
(93.8%) (75.0%) (50.0%) (87.5%) (93.8)
However, all the patients who underwent lateral peri insular functional hemispherotomy had multiple types of seizures (100.0% vs. 37.5%; p ¼ 0.035). A comparison between both the surgery groups for etiology is summarized in Table 2. 3.2. Development and psychological variables None of the children who underwent lateral peri insular functional hemispherotomy scored good in IQ test, similarly majority of the children (81.3%) who underwent VPH scored poorly on IQ test. The score for QOLIE used to assess QOL were good only in one child in the entire group. Comparison between groups for various psychosocial variables is summarized in Table 1. In the entire cohort, there was significant improvement in the average mental age post surgery (3.82 ± 1.60 years vs 4.46 ± 1.79 years; p < 0.001), social age (3.52 ± 1.69 years vs 4.46 ± 1.83 years; p < 0.001), social quotient (52.45 ± 23.29 vs 59.00 ± 22.32 years; p ¼ 0.006) and developmental quotient (55.65 ± 20.59 vs 59.05 ± 20.95 years; p ¼ 0.001). Furthermore, scores on cognitive scale declined post-operatively in one patient and remained the same in four. 3.3. Post operative outcome The average blood loss during the surgery was higher in lateral peri insular functional hemispherotomy than VPH (548 ml vs.
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
4
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
Fig. 1. Comparison of seizure control between etiologies (N ¼ 21).
208 ml; p < 0.001) and a longer mean duration of surgery (318 vs. and 188 min; p < 0.001). Moreover, the average post operative length of stay in hospital was almost twice in patients who underwent lateral peri insular functional hemispherotomy when compared to patients in VPH group (19.16 vs. 10.25 days; p < 0.001). However, there was no difference between the groups for post operative complications (20.0% vs. 20.0%; p ¼ 1.000). All the children had hemiperesis prior to surgery. While, one patient who underwent lateral peri insular functional hemispherotomy reported increase in hemianopia, three patients in VPH group had further deterioration of motor weakness of the hemiparetic side, immediately at post surgery. One patient in the VPH group needed VP shunting a week after surgery due to worsening of sub-dural hygroma. One child developed cortical sinus venous thrombosis following hemispherotomy and needed decompressive craniectomy. There was no significant difference between the groups for the reported APOS (20.0% vs. 25.0%; p ¼ 1.000). The duration of followup ranged from 2 to 11 years. There was no difference between the groups for seizure freedom (60.0% vs. 87.5%; p ¼ 0.228), Table 3. When analyzed for outcome between the etiologies in the entire group, seizure control at discharge from hospital was similar for
gliosis due to presumed childhood infarct (76.9%), Rasmussen's encephalitis (83.3%) and MCD (100.0%), Fig. 1. Fig. 2 illustrates the steps of VPH and Fig. 3 depicts MR imaging at one year post VPH in a child with hemispherical epilepsy due to gliosis. One child with Hemispherical malformation who was not seizure free post surgery, underwent re-surgery 4 years post surgery; total callosotomy was performed based on DTI data showing incomplete callosotomy. At two years Scores in psychological tests improved in all the patients who underwent lateral peri insular functional hemispherotomy and in 93.8% patients who underwent VPH at two year follow up. Moreover, improved QOLIE score was observed in 80.0% of the functional group and 87.5% children in VPH group at long term follow up (summarized in Table 1.). Fig. 4 demonstrates results of the long term follow up of patients who underwent VPH.
4. Discussion In the current cohort of 21 children who underwent hemispherotomy at our center in South India, the results were similar to previously reported data from larger series. Hemispherotomy offers good outcome in seizure control and psychosocial behaviors at follow up. Findings in the current study of seizure freedom in more than 90.5% of the patients following hemispherotomy are similar to earlier reports of 52%e90% [2,23,24] in western population and 94% reported in Indian study [25]. Similarly, the findings of the current study that VPH has no serious intra operative complications and lesser blood loss are in concordance to findings reported in larger series [26]. Furthermore, our observation that hemispherotomy techniques differ for peri-operative risks and hospital stay but not post surgery seizure freedom agrees with findings in western population reported by Cook S.W. et al. [15] and in India by Chandra P.S. et al. [25]. We report that nearly 87% of our VPH patients are
Fig. 2. Intra-operative images of the stages of hemispherotomy a) Total callosotomy b)Sectioning of orbito-frontal connection c)Floor of trigone hippocampal section d)Vertical transaction from lateral ventricle to temporal horn.
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
5
Fig. 3. MRI image at one year post vertical para-sagittal hemispherotomy in a patient with right hemispherical atrophy with gliosis (presumed due to childhood infarct) causing refractory hemispherical epilepsy. a) Axial T2 weighted MRI brain. b) Coronal T2 weighted MRI brain.
seizure free at the time of discharge which is higher than that reported by Delalande et al. [1]. However, the same study reports that results vary according to the etiology which is also observed in the current study. Nearly two-thirds of the current study population had gliosis due to presumed childhood stroke as etiology; this probably is due to vasculitis subsequent to infections that are common among children in India [27]. Outcome pattern in the current study is similar to that previously reported in children with vascular etiology from western population [5]. In our study, we could not evaluate the association of etiology to outcome because of a smaller study population. For the same reason of a small study population, elaborate evaluation of clinical variables with outcome could not be established. Acute post operative seizures were observed in five (23.8%) of the children, similar to the 26% incidence reported by Mani et al. [10] who included both hemispherotomies and extratemporal resections. The same study reported that APOS is associated with poor outcome up to 24 months follow up. However, in the current study, only one child out of the five with APOS had unfavorable outcome.
The quality of life of approximately eighty five percent of the patients improved from their pre-operative status. Nearly, all the patients showed improved performance on psychological testing and nearly half of them returned back to school. In general, long duration of epilepsy is associated with poor functional outcome [4], but in the current study we could not find it possibly because most of the children in the current cohort had severe epilepsy thus necessitating surgery at a very young age. 4.1. Strengths and limitations Our study reflects clinical picture of hemispherotomy in children from a developing country and reflects true clinical practice. The pre-operative assessment of quality of life and psychological status could not be rigorous due difficulties in testing like young age, varying socio-economic factors and frequent seizures. Our analysis may have been under powered due to a small sample size hence caution must be exercised while evaluating consistency and applicability of findings of our study. Furthermore, we included multiple comparisons with a potential for inherent errors, however the findings seem to be clinically plausible. Despite these
Fig. 4. Long term follow up of the study population (n ¼ 21).
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
6
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
limitations, our study adds relevant information on functional outcome of children undergoing hemispherotomy in a developing country. 5. Conclusion In the current study, gliosis due to presumed childhood infarct was the leading cause of medically refractory epilepsy caused by hemispheric lesions. Encouragingly, hemispherotomy offers seizure freedom (in 90.5% patients) and improvement in QOLIE scores at two years follow up. Author contribution Sita Jayalakshmi e Study design and critical review of manuscript, SudhindraVooturi e Data analysis, Rammohan Vadapalli e Data collection and review, Shanmukhi Somayajula e Data collection, manuscript writing and review, Shyam Sundar Krishnan e Data collection and manuscript writing, Manas Panigrahi e Study design and critical review of manuscript.
[2]
[3]
[4]
[5]
[6]
[7] [8] [9] [10]
Sources of support [11]
None. [12]
Sources of funding [13]
None. Guarantor
[14]
[15]
Dr. Manas Panigrahi e Corresponding author. Conflict of interest None. Ethical approval
[16]
[17] [18] [19]
Institutional Ethics Committee e KIMS Foundation and Research Center. Reference No: KFRC/EC/MAY/2/2013.
[20] [21]
Research Registration Unique Identifying Number (UIN)
[22]
researchregistry98. [23]
ISRCTN [24]
Not applicable. [25]
Acknowledgment
[26]
None. [27]
References
G. Dorfmuller, I. Jambaque, Vertical parasagittal hemispherotomy: surgical procedures and clinical long-term outcomes in a population of 83 children, Neurosurgery 60 (2007). ONS19e32;discussion ONS32. A.M. Devlin, J.H. Cross, W. Harkness, W.K. Chong, B. Harding, F. Vargha-Khadem, B.G. Neville, Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence, Brain 126 (2003) 556e566. T. Hallbook, P. Ruggieri, C. Adina, D.K. Lachhwani, A. Gupta, P. Kotagal, W. E. Bingaman and E. Wyllie Contralateral MRI abnormalities in candidates for hemispherectomy for refractory epilepsy. Epilepsia 51:556e563. R. Jonas, S. Nguyen, B. Hu, R.F. Asarnow, C. LoPresti, S. Curtiss, S. de Bode, S. Yudovin, W.D. Shields, H.V. Vinters, G.W. Mathern, Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes, Neurology 62 (2004) 1712e1721. E.H. Kossoff, E.P. Vining, D.J. Pillas, P.L. Pyzik, A.M. Avellino, B.S. Carson, J.M. Freeman, Hemispherectomy for intractable unihemispheric epilepsy etiology vs outcome, Neurology 61 (2003) 887e890. D. Lettori, D. Battaglia, A. Sacco, C. Veredice, D. Chieffo, L. Massimi, T. Tartaglione, F. Chiricozzi, S. Staccioli, A. Mittica, C. Di Rocco, F. Guzzetta, Early hemispherectomy in catastrophic epilepsy: a neuro-cognitive and epileptic long-term follow-up, Seizure 17 (2008) 49e63. W.E. Dandy, Removal of right cerebral hemisphere for certain tumours with hemiplegia: preliminary report, J. Am. Med. Assoc. 90 (1928) 823e825. M. Danielpour, C.S. von Koch, S.G. Ojemann, W.J. Peacock, Disconnective hemispherectomy, Pediatr. Neurosurg. 35 (2001) 169e172. T. Rasmussen, Hemispherectomy for seizures revisited, Can. J. Neurol. Sci. 10 (1983) 71e78. J. Mani, A. Gupta, E. Mascha, D. Lachhwani, K. Prakash, W. Bingaman, E. Wyllie, Postoperative seizures after extratemporal resections and hemispherectomy in pediatric epilepsy, Neurology 66 (2006) 1038e1043. W.J. Peacock, M.C. Wehby-Grant, W.D. Shields, D.A. Shewmon, H.T. Chugani, R. Sankar, H.V. Vinters, Hemispherectomy for intractable seizures in children: a report of 58 cases, Childs Nerv. Syst. 12 (1996) 376e384. O.P. Delalande, J.M. Basdevant, C. Hemispherotomy: a new procedure for central disconnection, Epilepsia 33 (1992) 99e100. J.R. Smith, K.N. Fountas, M.R. Lee, Hemispherotomy: description of surgical technique, Childs Nerv. Syst. 21 (2005) 466e472. C. Di Rocco, A. Iannelli, Hemimegalencephaly and intractable epilepsy: complications of hemispherectomy and their correlations with the surgical technique. A report on 15 cases, Pediatr. Neurosurg. 33 (2000) 198e207. S.W. Cook, S.T. Nguyen, B. Hu, S. Yudovin, W.D. Shields, H.V. Vinters, B.M. Van de Wiele, R.E. Harrison, G.W. Mathern, Cerebral hemispherectomy in pediatric patients with epilepsy: comparison of three techniques by pathological substrate in 115 patients, J. Neurosurg. 100 (2004) 125e141. T. Maehara, H. Shimizu, K. Kawai, R. Shigetomo, K. Tamagawa, T. Yamada, M. Inoue, Postoperative development of children after hemispherotomy, Brain Dev. 24 (2002) 155e160. E. Wyllie, Surgical treatment of epilepsy in pediatric patients, Can. J. Neurol. Sci. 27 (2000) 106e110. E. Wyllie, Y.G. Comair, P. Kotagal, S. Raja, P. Ruggieri, Epilepsy surgery in infants, Epilepsia 37 (1996) 625e637. P. Gadgil and V. Udani Pediatric epilepsy: the Indian experience. J. Pediatr. Neurosci. 6:S126eS129. V. Udani, Pediatric epilepsy e an Indian perspective, Indian J. Pediatr. 72 (2005) 309e313. M.B. Rao, K. Radhakrishnan, Is epilepsy surgery possible in countries with limited resources? Epilepsia 41 (Suppl. 4) (2000) S31eS34. J. Engel, G.D. Cascino, P.C.V. Ness, T.B. Rasmussen, L.M. Ojemann, Outcome with respect to epileptic seizures, in: J. Engel (Ed.), Surgical Treatment of the Epilepsies, Raven Press, NY, 1993. S.N. Basheer, M.B. Connolly, A. Lautzenhiser, E.M. Sherman, G. Hendson, P. Steinbok, Hemispheric surgery in children with refractory epilepsy: seizure outcome, complications, and adaptive function, Epilepsia 48 (2007) 133e140. H. Shimizu, Our experience with pediatric epilepsy surgery focusing on corpus callosotomy and hemispherotomy, Epilepsia 46 (Suppl. 1) (2005) 30e31. P.S. Chandra, V.M. Padma, G. Shailesh, B. Chandreshekar, C. Sarkar, M. Tripathi, Hemispherotomy for intractable epilepsy, Neurol. India 56 (2008) 127e132. C. Dorfer, T. Czech, A. Dressler, G. Groppel, A. Muhlebner-Fahrngruber, K. Novak, A. Reinprecht, E. Reiter-Fink, T. Traub-Weidinger, M. Feucht, Vertical perithalamic hemispherotomy: a single-center experience in 40 pediatric patients with epilepsy, Epilepsia 54 (1905-1912). R.N. Sahu, R. Kumar, A.K. Mahapatra, Central nervous system infection in the pediatric population, J. Pediatr. Neurosci. 4 (2009) 20e24.
[1] O. Delalande, C. Bulteau, G. Dellatolas, M. Fohlen, C. Jalin, V. Buret, D. Viguier,
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
Contents lists available at ScienceDirect
International Journal of Surgery journal homepage: www.journal-surgery.net
Original research
An observational study on outcome of hemispherotomy in children with refractory epilepsy Manas Panigrahi a, *, Shyam Sundar Krishnan a, Sudhindra Vooturi b, Rammohan Vadapalli c, Shanmukhi Somayajula b, Sita Jayalakshmi b a b c
Department of Neurosurgery, Krishna Institute of Medical Sciences, Minister Road, Secunderabad, 03 Telangana, India Department of Neurology, Krishna Institute of Medical Sciences, Minister Road, Secunderabad, 03 Telangana, India Department of Radiology, Vijaya Diagnostic Centre, Hyderabad, India
h i g h l i g h t s Retrospective analysis of data in 21 children who underwent hemispherotomy. Gliosis was most common etiology, observed in 13 (62.0%) of the children. Improved QOLIE scores was observed in nearly 85% children at last follow-up. Hemispherotomy offers good outcome in psychosocial behaviors at follow up.
a r t i c l e i n f o
a b s t r a c t
Article history: Received 1 April 2015 Received in revised form 15 May 2015 Accepted 29 May 2015 Available online xxx
Introduction: The current study aimed to evaluate the clinical characteristics and outcome of hemispherotomy in children with refractory hemispherical epilepsy. Methods: Retrospective analysis of data in twenty one children aged 12 years who underwent hemispherotomy and had at least two years post surgery follow-up was performed. Sixteen children underwent Delalande's vertical para-sagittal hemispherotomy (VPH), while lateral peri-insular functional hemispherotomy was performed in the rest. Results & discussion: The average age of onset for epilepsy in the study population was 2.9 ± 2.4 years; the average duration of epilepsy was 4.0 ± 2.9 years. The mean age at surgery of the study population was 6.8 ± 2.8 years. Six (28.5%) children were girls. Gliosis due to presumed childhood infarct was most common etiology, observed in 13 (62.0%) of the children, followed by Rasmussen's encephalitis in six (28.5%). There was no significant difference between the surgery groups for the reported acute post operative seizures (APOS) (20.0% vs. 25.0%; p ¼ 1.000). At last follow up 90.5% patients were seizure free; there was no difference between the groups for seizure freedom (60.0% vs. 87.5%; p ¼ 0.228). When analyzed for outcome between the etiologies, seizure freedom was similar for gliosis due to infarct (76.9%), Rassmussens encephalitis (83.3%) and malformations of cortical development (MCD) (100.0%). Moreover, improved quality of life in epilepsy (QOLIE) scores was observed in 80.0% of the lateral periinsular functional hemispherotomy group and 87.5% children in VPH group at the last follow-up. Conclusion: Gliosis due to presumed childhood infarct was the leading cause of medically refractory epilepsy caused by hemispheric lesions in the current study. Encouragingly, hemispherotomy offers seizure freedom (in 90.5% patients) and improvement in QOLIE scores at two years follow up. © 2015 Published by Elsevier Ltd on behalf of IJS Publishing Group Limited.
Keywords: Hemispherotomy Outcome in children Gliosis Refractory SE
1. Introduction
* Corresponding author. Krishna Institute of Medical Sciences, 1-8-31/1, Ministers Road, Secunderabad, Telangana 500003, India. E-mail address: [email protected] (M. Panigrahi).
Hemispherectomy is a proven treatment for medically refractory epilepsies due to congenital or acquired hemispheric or multilobar epileptogenic lesions with a current success rate of 50e80% [1e6]. Walter Dandy [7] in 1928 reported the use of
http://dx.doi.org/10.1016/j.ijsu.2015.05.049 1743-9191/© 2015 Published by Elsevier Ltd on behalf of IJS Publishing Group Limited.
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
2
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
cerebral hemispherectomy in patients with intractable unihemisphereic lesions. However, limited resections and disconnections were largely preferred by 1980s after complications of classic anatomical hemispherectomy like obstructive hydrocephalus, haemosiderosis and intracranial haematoma were reported in nearly 30% of the patients [8,9]. After the introduction of functional hemispherectomy by Rasmussen et al. [9], in 1974 the morbidity and mortality declined however at similar seizure outcome when compared to classic anatomic hemispherectomy [2,10e12]. Delalande et al. [12] later described less invasive technique of hemispherotomy for which variations were subsequently proposed [13]. This evolution progressed to more recent techniques like, vertical para-sagittal hemispherotomy and Peri -insular hemispherotomy in efforts to reduce morbidity while preserving efficacy [1e4]. When comparing various surgical techniques, existing literature indicates that hemispherotomy is associated with fewer complications than functional hemispherectomy [14]. When compared for the seizure outcome between the groups, while few studies have reported non-significant difference between functional hemispherectomy and hemispherotomy [15], multi center trials with large series have reported significantly more number of patients undergoing hemispherotomy as seizure-free as the functional hemispherectomy groups. Encouragingly, an increasing number of studies show that hemispherotomy is associated with improvements in post-operative development, quality of life (QOL) and adaptive behaviors in children by reducing the seizure frequency [16e18]. Disparities in aetiology have been reported in developing countries and even within a given developing country [19]. Major differences between developing and developed world exist in access to and availability of epilepsy management programs, which are very limited in developing world [20]. Implementing surgical strategies in developing countries in a large scale is very essential given the fact that epilepsy surgeries like anterior temporal lobectomy has been proved to be more feasible and cost-effective than medical management of refractory status epilepticus in developing countries [21]. However, very limited literature exists on the role of hemispherotomy in developing countries where the probability of medically refractory hemispherical epilepsy patient being young, fully contributing members of society is higher. Therefore, fewer the complication the more desirable is the surgical intervention.
seizures, history of neonatal seizures, febrile convulsions, status epilepticus and clinical findings of neurological examination. In children aged above 2 years, developmental quotient (DQ), social quotient (SQ), and intelligence quotient (IQ) were assessed using standardized tests like developmental screening test, vineland social maturity scale, Binet-Kamath Intelligence Scale, Furthermore, quality of life (QOL) was assessed using quality of life in epilepsy (QOLIE 48) where a score of more than fifty of a maximum of hundred points was considered as good outcome. A parental interview was done to evaluate further about child's behavior, cognitive abilities, physical and neurological disability. Montreal handedness test, behavioral problem assessment, and psychiatric evaluation according to international classification of diseases (ICD10) were performed. Imaging of brain was done with 1.5 T MRI in six and 3 T MRI in the remaining children. Functional MRI for language mapping was done in two and for motor mapping in six children. All the children underwent pre and post surgery diffusion tensor imaging (DTI) with tractography. All the children underwent prolonged videoEEG (VEEG) monitoring. Ictal single photon emission computed tomography (SPECT) was performed in ten children, eight children underwent interictal fluoro deoxy-D-glucose positron emission tomography (FDG PET). Interictal spikes were grouped as unilateral (>75% on the ipsilateral side of the imaging abnormality) and multifocal.
1.1. Aim
2.4. Statistical analysis
The current study aimed to evaluate the clinical characteristics and outcome of functional hemispherotomy in Indian children with medically refractory hemispherical epilepsy syndromes.
All continuous variables are expressed as mean ± SD. All the categorical variables are expressed as frequencies and percentages. The distribution of the study variables and outcome of the entire study population is depicted using frequency distribution charts. All the study variables were compared between the two types of surgeries; where paired student t-test was used to compare for continuous variables before and after the surgery and unpaired student t-test was used to compare continuous variables between the surgery groups. Chi-square test was used to compare between the surgeries for categorical variables. A p value of 0.05 was considered significant. Statistical analysis was done using Statistical Software for Social Sciences (SPSS, version 17.0 IBM Computers, NewYork, USA).
2. Materials & methods Retrospective analysis of data of twenty two children aged 12 years and below, who underwent hemispherotomy at Krishna Institute of Medical Sciences, a tertiary referral care centre in South India was done. All the children had at least two years post surgery follow-up. The presurgical, surgical and post-surgical variables were included in the data analysis. One child died at day 10 of the hospital stay and was subsequently excluded from analysis of long term outcome. The study was approved after review by the institutional ethics committee. 2.1. Pre surgical evaluation The clinical evaluation included variables such as age at surgery, gender, aetiology, age of onset of epilepsy, type and frequency of
2.2. Surgery Sixteen children underwent Delalande's vertical para-sagittal Hemispherotomy (VPH) while lateral peri insular functional hemispherectomy was performed in five children. 2.3. Post surgical evaluation and outcome The post-operative hospital course, complications, and functional outcome data were collected and analyzed. Acute postoperative seizures (APOS) were defined as seizures occurring within 7 days after surgery. All the patients were assessed for IQ, development, and behavioral problems and quality of life at three months and one year post surgery. The outcome at the last follow up was assessed using to the Engel's outcome classification where Engel's class I was considered seizure free [22].
3. Results In the current study on 21 children who underwent hemispherotomy at our center and followed up for a mean 25.4 ± 1.5 months post surgery, the average age of onset of epilepsy was 2.9 ± 2.4 years; the average duration of epilepsy was 4.0 ± 2.9 years.
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
3
Table 1 Comparison between surgical approaches for clinical and demographic variables. S.No
Variable
Lateral peri insular functional hemispherotomy (n ¼ 5)
Vertical para-sagittal hemispherotomy (n ¼ 16)
p value
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
Female (%) Age (years) Age of onset (years) Neonatal onset of seizures (%) Duration of epilepsy Febrile convulsions (%) Childhood insult (%) Multiple types of seizures (%) Low IQ of <75 (%) Good quality of life (%) Psychiatric co-morbidities (%) Developmental delay (%) History of status epilepticus (%) Family history of epilepsy (%) Daily Seizures (%) Hemiparesis (%)
0 (0.0%) 8.0 ± 2.9 3.2 ± 2.3 1 (20.0%) 4.6 ± 2.0 1 (20.0%) 1 (20.0%) 3 (21.4%) 5 (100.0%) 0 (0.0%) 0 (0.0%) 4 (80.0%) 3 (60.0%) 0 (0.0%) 5 (100.0%) 4 (80.0%)
6(37.5%) 6.5 ± 2.7 2.9 ± 2.5 2 (12.5%) 3.8 ± 3.2 2 (12.5%) 6 (37.5%) 11 (78.6%) 13 (81.3%) 1 (6.3%) 12 (80.0%) 9 (56.3%) 5 (31.3%) 4 (25.0%) 14 (87.5%) 15 (93.8%)
0.262 0.303 0.829 1.000 0.636 1.000 0.624 1.000 0.549 1.000 0.004 0.606 0.325 0.532 1.000 0.429
Table 2 Comparison between surgical approaches for etiology (n ¼ 21). Lateral peri insular functional hemispherotomy (n ¼ 5) Vertical para-sagittal hemispherotomy (n ¼ 16) p value
S.No Variable 1 2 3 4 5 6 7
Gliosis due to presumed childhood infarct (%) 3 (60.0%) Rasmussen's encephalitis (%) 1 (20.0%) Hemispherical malformation (%) 1 (20.0%) Acute post operative seizures(%) 1 (20.0%) Interi-ictal EEG concordant (%) 2 (40.0%) Multiple types of seizures (%) 5 (100.0%) Ictal EEG concordant(%) 2 (40.0%)
10 5 1 4 9 6 11
(62.5%) (31.3%) (6.3%) (25.0%) (56.3%) (37.5%) (68.8%)
1.000 1.000 0.428 1.000 0.635 0.035 0.325
Table 3 Comparison between surgical approaches types for outcome (n ¼ 21). S.No
Variable
Lateral peri insular functional hemispherotomy (n ¼ 5)
Vertical para-sagittal hemispherotomy (n ¼ 16)
p value
1 2 3 4 5
Seizure free at last follow up (%) Improved cognition (%) Back to school (%) Good long term QOLIE (%) Improved psychological score (%)
4 4 2 4 5
15 12 8 14 15
0.429 1.000 1.000 1.000 1.000
(80.0%) (80.0%) (40.0%) (80.0%) (100.0%)
The mean age at surgery of the study population was 6.8 ± 2.8 years with six (28.5%) female patients. While five (23.8%) children underwent lateral peri insular functional hemispherotomy, the remaining 16 (76.2%) patients underwent VPH. At last follow up 19 children were seizure free. While 11 (52.3%) children were off antiepileptic drugs (AEDs), rest of the children needed fewer than half the original number of AEDs. Encouragingly, 16 (76.2%) children reported improved cognitive function and 20 (95.2%) children scored better in psychological tests. 3.1. Demographic and clinical variables There were no significant differences between the groups for number of women (0.0% vs. 37.5%; p ¼ 0.262), age of onset of epilepsy (3.2 ± 2.3 vs. 2.9 ± 2.5; p ¼ 0.829) and age at surgery (8.0 ± 2.9 vs. 6.5 ± 2.7; p ¼ 0.303). Family history of epilepsy (0.0% vs. 25%; p ¼ 0.532) and history of childhood insult (20.0% vs. 37.5%; p ¼ 0.624) was similar among both the groups. Moreover, both the groups did not differ for children with multiple types of seizures (60.0% vs. 78.6%; p ¼ 1.000) and children who reported daily seizures (100.0% vs. 87.5%; p ¼ 1.000), Table 1. Distribution of etiologies of Rasmussen's encephalitis (20.0% vs. 31.3%; p ¼ 1.000), gliosis due to presumed childhood infarct (60.0% vs. 62.5%; p ¼ 1.000) and malformations of cortical development (MCD) (20.0% vs. 6.3%; p ¼ 0.428) was similar between both the groups.
(93.8%) (75.0%) (50.0%) (87.5%) (93.8)
However, all the patients who underwent lateral peri insular functional hemispherotomy had multiple types of seizures (100.0% vs. 37.5%; p ¼ 0.035). A comparison between both the surgery groups for etiology is summarized in Table 2. 3.2. Development and psychological variables None of the children who underwent lateral peri insular functional hemispherotomy scored good in IQ test, similarly majority of the children (81.3%) who underwent VPH scored poorly on IQ test. The score for QOLIE used to assess QOL were good only in one child in the entire group. Comparison between groups for various psychosocial variables is summarized in Table 1. In the entire cohort, there was significant improvement in the average mental age post surgery (3.82 ± 1.60 years vs 4.46 ± 1.79 years; p < 0.001), social age (3.52 ± 1.69 years vs 4.46 ± 1.83 years; p < 0.001), social quotient (52.45 ± 23.29 vs 59.00 ± 22.32 years; p ¼ 0.006) and developmental quotient (55.65 ± 20.59 vs 59.05 ± 20.95 years; p ¼ 0.001). Furthermore, scores on cognitive scale declined post-operatively in one patient and remained the same in four. 3.3. Post operative outcome The average blood loss during the surgery was higher in lateral peri insular functional hemispherotomy than VPH (548 ml vs.
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
4
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
Fig. 1. Comparison of seizure control between etiologies (N ¼ 21).
208 ml; p < 0.001) and a longer mean duration of surgery (318 vs. and 188 min; p < 0.001). Moreover, the average post operative length of stay in hospital was almost twice in patients who underwent lateral peri insular functional hemispherotomy when compared to patients in VPH group (19.16 vs. 10.25 days; p < 0.001). However, there was no difference between the groups for post operative complications (20.0% vs. 20.0%; p ¼ 1.000). All the children had hemiperesis prior to surgery. While, one patient who underwent lateral peri insular functional hemispherotomy reported increase in hemianopia, three patients in VPH group had further deterioration of motor weakness of the hemiparetic side, immediately at post surgery. One patient in the VPH group needed VP shunting a week after surgery due to worsening of sub-dural hygroma. One child developed cortical sinus venous thrombosis following hemispherotomy and needed decompressive craniectomy. There was no significant difference between the groups for the reported APOS (20.0% vs. 25.0%; p ¼ 1.000). The duration of followup ranged from 2 to 11 years. There was no difference between the groups for seizure freedom (60.0% vs. 87.5%; p ¼ 0.228), Table 3. When analyzed for outcome between the etiologies in the entire group, seizure control at discharge from hospital was similar for
gliosis due to presumed childhood infarct (76.9%), Rasmussen's encephalitis (83.3%) and MCD (100.0%), Fig. 1. Fig. 2 illustrates the steps of VPH and Fig. 3 depicts MR imaging at one year post VPH in a child with hemispherical epilepsy due to gliosis. One child with Hemispherical malformation who was not seizure free post surgery, underwent re-surgery 4 years post surgery; total callosotomy was performed based on DTI data showing incomplete callosotomy. At two years Scores in psychological tests improved in all the patients who underwent lateral peri insular functional hemispherotomy and in 93.8% patients who underwent VPH at two year follow up. Moreover, improved QOLIE score was observed in 80.0% of the functional group and 87.5% children in VPH group at long term follow up (summarized in Table 1.). Fig. 4 demonstrates results of the long term follow up of patients who underwent VPH.
4. Discussion In the current cohort of 21 children who underwent hemispherotomy at our center in South India, the results were similar to previously reported data from larger series. Hemispherotomy offers good outcome in seizure control and psychosocial behaviors at follow up. Findings in the current study of seizure freedom in more than 90.5% of the patients following hemispherotomy are similar to earlier reports of 52%e90% [2,23,24] in western population and 94% reported in Indian study [25]. Similarly, the findings of the current study that VPH has no serious intra operative complications and lesser blood loss are in concordance to findings reported in larger series [26]. Furthermore, our observation that hemispherotomy techniques differ for peri-operative risks and hospital stay but not post surgery seizure freedom agrees with findings in western population reported by Cook S.W. et al. [15] and in India by Chandra P.S. et al. [25]. We report that nearly 87% of our VPH patients are
Fig. 2. Intra-operative images of the stages of hemispherotomy a) Total callosotomy b)Sectioning of orbito-frontal connection c)Floor of trigone hippocampal section d)Vertical transaction from lateral ventricle to temporal horn.
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
5
Fig. 3. MRI image at one year post vertical para-sagittal hemispherotomy in a patient with right hemispherical atrophy with gliosis (presumed due to childhood infarct) causing refractory hemispherical epilepsy. a) Axial T2 weighted MRI brain. b) Coronal T2 weighted MRI brain.
seizure free at the time of discharge which is higher than that reported by Delalande et al. [1]. However, the same study reports that results vary according to the etiology which is also observed in the current study. Nearly two-thirds of the current study population had gliosis due to presumed childhood stroke as etiology; this probably is due to vasculitis subsequent to infections that are common among children in India [27]. Outcome pattern in the current study is similar to that previously reported in children with vascular etiology from western population [5]. In our study, we could not evaluate the association of etiology to outcome because of a smaller study population. For the same reason of a small study population, elaborate evaluation of clinical variables with outcome could not be established. Acute post operative seizures were observed in five (23.8%) of the children, similar to the 26% incidence reported by Mani et al. [10] who included both hemispherotomies and extratemporal resections. The same study reported that APOS is associated with poor outcome up to 24 months follow up. However, in the current study, only one child out of the five with APOS had unfavorable outcome.
The quality of life of approximately eighty five percent of the patients improved from their pre-operative status. Nearly, all the patients showed improved performance on psychological testing and nearly half of them returned back to school. In general, long duration of epilepsy is associated with poor functional outcome [4], but in the current study we could not find it possibly because most of the children in the current cohort had severe epilepsy thus necessitating surgery at a very young age. 4.1. Strengths and limitations Our study reflects clinical picture of hemispherotomy in children from a developing country and reflects true clinical practice. The pre-operative assessment of quality of life and psychological status could not be rigorous due difficulties in testing like young age, varying socio-economic factors and frequent seizures. Our analysis may have been under powered due to a small sample size hence caution must be exercised while evaluating consistency and applicability of findings of our study. Furthermore, we included multiple comparisons with a potential for inherent errors, however the findings seem to be clinically plausible. Despite these
Fig. 4. Long term follow up of the study population (n ¼ 21).
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049
6
M. Panigrahi et al. / International Journal of Surgery xxx (2015) 1e6
limitations, our study adds relevant information on functional outcome of children undergoing hemispherotomy in a developing country. 5. Conclusion In the current study, gliosis due to presumed childhood infarct was the leading cause of medically refractory epilepsy caused by hemispheric lesions. Encouragingly, hemispherotomy offers seizure freedom (in 90.5% patients) and improvement in QOLIE scores at two years follow up. Author contribution Sita Jayalakshmi e Study design and critical review of manuscript, SudhindraVooturi e Data analysis, Rammohan Vadapalli e Data collection and review, Shanmukhi Somayajula e Data collection, manuscript writing and review, Shyam Sundar Krishnan e Data collection and manuscript writing, Manas Panigrahi e Study design and critical review of manuscript.
[2]
[3]
[4]
[5]
[6]
[7] [8] [9] [10]
Sources of support [11]
None. [12]
Sources of funding [13]
None. Guarantor
[14]
[15]
Dr. Manas Panigrahi e Corresponding author. Conflict of interest None. Ethical approval
[16]
[17] [18] [19]
Institutional Ethics Committee e KIMS Foundation and Research Center. Reference No: KFRC/EC/MAY/2/2013.
[20] [21]
Research Registration Unique Identifying Number (UIN)
[22]
researchregistry98. [23]
ISRCTN [24]
Not applicable. [25]
Acknowledgment
[26]
None. [27]
References
G. Dorfmuller, I. Jambaque, Vertical parasagittal hemispherotomy: surgical procedures and clinical long-term outcomes in a population of 83 children, Neurosurgery 60 (2007). ONS19e32;discussion ONS32. A.M. Devlin, J.H. Cross, W. Harkness, W.K. Chong, B. Harding, F. Vargha-Khadem, B.G. Neville, Clinical outcomes of hemispherectomy for epilepsy in childhood and adolescence, Brain 126 (2003) 556e566. T. Hallbook, P. Ruggieri, C. Adina, D.K. Lachhwani, A. Gupta, P. Kotagal, W. E. Bingaman and E. Wyllie Contralateral MRI abnormalities in candidates for hemispherectomy for refractory epilepsy. Epilepsia 51:556e563. R. Jonas, S. Nguyen, B. Hu, R.F. Asarnow, C. LoPresti, S. Curtiss, S. de Bode, S. Yudovin, W.D. Shields, H.V. Vinters, G.W. Mathern, Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes, Neurology 62 (2004) 1712e1721. E.H. Kossoff, E.P. Vining, D.J. Pillas, P.L. Pyzik, A.M. Avellino, B.S. Carson, J.M. Freeman, Hemispherectomy for intractable unihemispheric epilepsy etiology vs outcome, Neurology 61 (2003) 887e890. D. Lettori, D. Battaglia, A. Sacco, C. Veredice, D. Chieffo, L. Massimi, T. Tartaglione, F. Chiricozzi, S. Staccioli, A. Mittica, C. Di Rocco, F. Guzzetta, Early hemispherectomy in catastrophic epilepsy: a neuro-cognitive and epileptic long-term follow-up, Seizure 17 (2008) 49e63. W.E. Dandy, Removal of right cerebral hemisphere for certain tumours with hemiplegia: preliminary report, J. Am. Med. Assoc. 90 (1928) 823e825. M. Danielpour, C.S. von Koch, S.G. Ojemann, W.J. Peacock, Disconnective hemispherectomy, Pediatr. Neurosurg. 35 (2001) 169e172. T. Rasmussen, Hemispherectomy for seizures revisited, Can. J. Neurol. Sci. 10 (1983) 71e78. J. Mani, A. Gupta, E. Mascha, D. Lachhwani, K. Prakash, W. Bingaman, E. Wyllie, Postoperative seizures after extratemporal resections and hemispherectomy in pediatric epilepsy, Neurology 66 (2006) 1038e1043. W.J. Peacock, M.C. Wehby-Grant, W.D. Shields, D.A. Shewmon, H.T. Chugani, R. Sankar, H.V. Vinters, Hemispherectomy for intractable seizures in children: a report of 58 cases, Childs Nerv. Syst. 12 (1996) 376e384. O.P. Delalande, J.M. Basdevant, C. Hemispherotomy: a new procedure for central disconnection, Epilepsia 33 (1992) 99e100. J.R. Smith, K.N. Fountas, M.R. Lee, Hemispherotomy: description of surgical technique, Childs Nerv. Syst. 21 (2005) 466e472. C. Di Rocco, A. Iannelli, Hemimegalencephaly and intractable epilepsy: complications of hemispherectomy and their correlations with the surgical technique. A report on 15 cases, Pediatr. Neurosurg. 33 (2000) 198e207. S.W. Cook, S.T. Nguyen, B. Hu, S. Yudovin, W.D. Shields, H.V. Vinters, B.M. Van de Wiele, R.E. Harrison, G.W. Mathern, Cerebral hemispherectomy in pediatric patients with epilepsy: comparison of three techniques by pathological substrate in 115 patients, J. Neurosurg. 100 (2004) 125e141. T. Maehara, H. Shimizu, K. Kawai, R. Shigetomo, K. Tamagawa, T. Yamada, M. Inoue, Postoperative development of children after hemispherotomy, Brain Dev. 24 (2002) 155e160. E. Wyllie, Surgical treatment of epilepsy in pediatric patients, Can. J. Neurol. Sci. 27 (2000) 106e110. E. Wyllie, Y.G. Comair, P. Kotagal, S. Raja, P. Ruggieri, Epilepsy surgery in infants, Epilepsia 37 (1996) 625e637. P. Gadgil and V. Udani Pediatric epilepsy: the Indian experience. J. Pediatr. Neurosci. 6:S126eS129. V. Udani, Pediatric epilepsy e an Indian perspective, Indian J. Pediatr. 72 (2005) 309e313. M.B. Rao, K. Radhakrishnan, Is epilepsy surgery possible in countries with limited resources? Epilepsia 41 (Suppl. 4) (2000) S31eS34. J. Engel, G.D. Cascino, P.C.V. Ness, T.B. Rasmussen, L.M. Ojemann, Outcome with respect to epileptic seizures, in: J. Engel (Ed.), Surgical Treatment of the Epilepsies, Raven Press, NY, 1993. S.N. Basheer, M.B. Connolly, A. Lautzenhiser, E.M. Sherman, G. Hendson, P. Steinbok, Hemispheric surgery in children with refractory epilepsy: seizure outcome, complications, and adaptive function, Epilepsia 48 (2007) 133e140. H. Shimizu, Our experience with pediatric epilepsy surgery focusing on corpus callosotomy and hemispherotomy, Epilepsia 46 (Suppl. 1) (2005) 30e31. P.S. Chandra, V.M. Padma, G. Shailesh, B. Chandreshekar, C. Sarkar, M. Tripathi, Hemispherotomy for intractable epilepsy, Neurol. India 56 (2008) 127e132. C. Dorfer, T. Czech, A. Dressler, G. Groppel, A. Muhlebner-Fahrngruber, K. Novak, A. Reinprecht, E. Reiter-Fink, T. Traub-Weidinger, M. Feucht, Vertical perithalamic hemispherotomy: a single-center experience in 40 pediatric patients with epilepsy, Epilepsia 54 (1905-1912). R.N. Sahu, R. Kumar, A.K. Mahapatra, Central nervous system infection in the pediatric population, J. Pediatr. Neurosci. 4 (2009) 20e24.
[1] O. Delalande, C. Bulteau, G. Dellatolas, M. Fohlen, C. Jalin, V. Buret, D. Viguier,
Please cite this article in press as: M. Panigrahi, et al., An observational study on outcome of hemispherotomy in children with refractory epilepsy, International Journal of Surgery (2015), http://dx.doi.org/10.1016/j.ijsu.2015.05.049