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Resective surgery is possible in patients with temporal lobe epilepsy due to bilateral isolated hippocampal malformation
Clinical Neurology and Neurosurgery 111 (2009) 554–557
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Resective surgery is possible in patients with temporal lobe epilepsy due to bilateral isolated hippocampal malformation Nese Dericioglu a,∗ , Kader Karli Oguz b , Figen Soylemezoglu c , Nejat Akalan d , Serap Saygi e a
Hacettepe University, Institute of Neurological Sciences and Psychiatry, Department of Neurology, Sihhiye 06100, Ankara, Turkey Hacettepe University School of Medicine, Department of Radiology, Turkey c Hacettepe University School of Medicine, Department of Pathology, Turkey d Hacettepe University School of Medicine, Department of Neurosurgery, Turkey e Hacettepe University School of Medicine, Department of Neurology, Turkey b
a r t i c l e
i n f o
Article history: Received 20 October 2008 Received in revised form 2 March 2009 Accepted 3 March 2009 Keywords: Temporal lobe epilepsy Bilateral hippocampal malformation Surgery Pathology Prognosis
a b s t r a c t Various hippocampal malformations have been described in the context of widespread cortical malformations in patients with epilepsy. Isolated hippocampal malformations however are very rarely identified on MR imaging studies. Little is known about the epileptogenicity of these malformations and their pathologic appearance. We present a case with severe bilateral hippocampal malformations who underwent right temporal lobectomy due to intractable temporal lobe epilepsy. Postoperative examination of the resected hippocampus revealed abnormal shape of the dentate gyrus and an atypical convolution of the CA1 pyramidal cell-subicular layers. After surgery, the patient has been seizure free. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults and is usually accompanied by hippocampal sclerosis (HS). Temporal lobectomy renders most of these patients seizure free, indicating that mesial temporal structures are somehow involved in the pathophysiology of epilepsy. Recently developmental malformations of the hippocampus have been recognized increasingly on magnetic resonance (MR) imaging [1–7] in patients with epilepsy and are not infrequently accompanied by cortical malformations. However isolated hippocampal malformations are extremely rare. Unlike HS, it is not well known to what extent the malformed hippocampus contributes to the generation of seizures. Given that some of the hippocampal structures commonly involved in seizures in HS (e.g. dentate gyrus, CA1, and subiculum) are altered in malformed hippocampi, it is possible that the malformed hippocampus may be involved in seizure generation and/or propagation. So far, very few studies have reported the postoperative outcome in patients with hippocampal malformation [1,3], and outcome is similar to patients with HS [3]. Although MR imaging criteria for the abnormal shape and positioning of the hippocampal formation (HF) have been well described [2,6], the
∗ Corresponding author. Tel.: +90 312 305 1182; fax: +90 312 309 3451. E-mail address: [email protected] (N. Dericioglu). 0303-8467/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2009.03.002
microscopic correlates are less clear [3,7]. Here we present the clinical and laboratory findings of a patient with TLE and severe bilateral isolated malformation of the hippocampi who has been seizure free on medications for 2 years after right temporal lobectomy with amygdalo-hippocampectomy. 2. Case report A 22-year-old female patient was admitted for long term videoEEG monitoring due to intractable seizures that had started at the age of 13. She was the product of an unrelated couple. The prenatal history was normal, however delivery was difficult. Her developmental milestones were normal and at the time of admission she was a university student. One of her cousins also had epilepsy, which could not be further identified. Otherwise her personal and family histories were unremarkable. She had partial seizures with oral automatisms, during which consciousness was preserved. She reported de ja vu prior to some of her seizures that were not controlled with various combinations of carbamazepine (CBZ), phenobarbital, valproate, lamotrigine, levetiracetam (LEV) and topiramate. On admission, she was on CBZ (1000 mg/day) and LEV (1000 mg/day). Three partial seizures were captured within 4 days. Her seizures occurred during wakefulness and the ictal semiologic characteristics were similar in all of them. She had oral automatisms during most of the seizures. At the onset of the second and third
N. Dericioglu et al. / Clinical Neurology and Neurosurgery 111 (2009) 554–557
555
Fig. 1. On coronal T2-weighted imaging (TR/TE: 4800/100 ms) (A and B) and coronal three-dimensional GRE (TR/TE/TI: 2000/4.4/1100 ms, flip angle:10◦ ) (C and D) bilateral severe hippocampal malformation is seen. Please note the presence of disoriented sulci along the inferiomedial temporal lobe.
seizures she hyperventilated and screamed, elevated her left leg and extended both arms. During the seizures she was able to answer all the questions or obeyed the commands. The interictal EEG revealed rare sharp wave paroxysms in the right anterior temporal region. Ictal EEG onset was characterized by irregular 2.5–3 Hz slow waves in the right fronto-temporal region during the first seizure; about 4–5 Hz rhythmic slow waves in the right anterior temporal region during the second seizure and high amplitude rhythmic 2 Hz delta waves in the right fronto-temporal area during the last seizure. After the initial changes, a build-up characterized by 5–7 Hz rhythmic sharp waves in the right temporal region appeared in all of the seizures. MR imaging performed at a 3T imager (Allegra, Siemens, Erlangen, Germany) revealed bilateral malrotation of the hippocampi with accompanying abnormal sulcation along the floor of the medial temporal lobe (Fig. 1A–D). Absence of horizontally located ovoid hippocampi with empty choroid fissures, medial location of the hippocampi, vertically oriented collateral sulci, short parahippocampal gyri and thin collateral white matter were the findings suggesting malrotation of the hippocampi as described by Baulac
et al. in 1998 [1]. Other functional neuro-imaging tests (e.g. PET and SPECT) were not performed. Regarding the neuropsychological findings, several preoperative tests were performed including AVLT, WMS-R, line orientation, Rey-Osterrieth complex figure and digit span. The test results indicated moderate impairment of the right temporal lobe functions, whereas left temporal functions were within normal limits. Based on clinical observation of the seizures and electrophysiologic data the patient underwent right anterior temporal lobectomy with amygdalo-hippocampectomy. The en bloc hippocampal resection was fixed in 10% formalin before routine processing in paraffin. Serial coronal sections 5-m-thick passing through the hippocampal formation were obtained and processed routinely. Care was taken to ensure that all hippocampal sections were cut in a plane perpendicular to the longitudinal axis of the hippocampus and the ones described in the study were from the body of the hippocampus. Sections were stained with hematoxylin and eosin (H&E) and with antisera against NeuN, which revealed an atypical convolution of CA1/subicular neurons (Fig. 2). The dentate gyrus had a very unusual shape, with some finger-like projections of granule cells into the surrounding
556
N. Dericioglu et al. / Clinical Neurology and Neurosurgery 111 (2009) 554–557
Fig. 2. NeuN staining revealed an atypical convolution of CA1 pyramidal neurons/subicular layers without obvious cell loss in the CA subfields. Note the angulated configuration of the dentate gyrus that is misplaced by the atypical indentation of CA1/subiculum layers (asterisk) (sub: subiculum, DG: dentate gyrus).
areas. There was minimal or no cell loss in the dentate hilus, and CA1–CA3 areas, unlike samples of HS. 3. Discussion We present a case with bilateral isolated hippocampal developmental abnormalities who underwent right temporal lobectomy with amygdalo-hippocampectomy due to TLE and has been seizurefree on medications for 2 years. High resolution cranial MR imaging has made it possible to detect subtle brain malformations and hippocampal shape abnormalities have been recognized increasingly during the last years. In different patient series the frequency of MR imaging defined malformations of hippocampal development (MHD) varies between 2.2% and 64% [2,3,6]. The rates seem to be much higher in patients with various malformations of cortical development [4,6]. In a recent study, bilaterality of hippocampal malrotation was reported in 12.5% of 32 cases who had been investigated for presumed epilepsy [2]. There is limited data regarding the neuropathological correlates of MHD in TLE [1,3,7]. In an adult patient with TLE who had bilateral hippocampal abnormalities on MR imaging, Thom et al. reported the autopsy findings of the HFs [7]. Histologic examination revealed that the hilus of the dentate gyrus was more vertical than horizontal on some levels. Complex foldings of CA1 appeared excessively long and serpiginous. There was no evidence of cell loss, dysplasia or gliosis. The dentate granule cell layer was well defined with minimal cell dispersion. In the series by Baulac et al. surgical resection and pathologic description were available for one patient, confirming hippocampal sclerosis in combination with an abnormally folded subiculum [1]. Finally, Sloviter et al. reported the pathological findings of the hippocampus/dentate gyrus in 16 patients with malformations of the HF [3]. The authors reported the presence of an atypical convolution of the CA1 pyramidal cell/subicular layers, similar to ours, and it appeared to invaginate or sometimes bisect the adjacent dentate gyrus. The granule cell layer exhibited unusual morphological features. Immunostaining revealed abnormal dentate gyrus lamination in segments containing the pyramidal cell layer anomaly. Interestingly, none of the hippocampi had abnormal configurations or locations on conventional MR imaging scan.
The MR imaging appearance of the HF in our patient had similarities to those reported by Kier et al. in human fetal brain, roughly corresponding to 18 weeks of gestation [8]. Among cortices, neurons destined for the hippocampal region are perhaps the earliest to be born, however in terms of neuroblast migration and cytoarchitectural maturation, the hippocampal region is late compared with much of the neocortex [9]. By 15–19 weeks, the hippocampus begins to flex over the parahippocampal gyrus, thus forming the hippocampal fissure. Subicular, ammonic, and dentate subfields are readily identifiable. By the end of gestation, the predominantly adultlike cytoarchitectural features of the various hippocampal subfields are present, with only several minor differences. The hippocampus remains qualitatively similar after the ninth postnatal month. The mechanisms resulting in MHD are not well known, but it has been hypothesized that disturbances in mechanical forces with increased brain size and/or specific factors influencing gyrogenesis may be involved. The bilateral MHD in our patient may have resulted from an unidentified insult occurring early in development. It is interesting though that the hippocampal malformations were isolated and not accompanied by other cortical developmental pathologies. That similar pathological findings of the HF without macroscopic malformations of the brain were described earlier by Amano et al. in a novel rat mutant with spontaneous limbic-like seizures [10] also suggests that some kind of genetic mutation may be responsible. It is not known to what extent the malformation represents the epileptogenic tissue, because not all brain malformations are potentially epileptogenic and some may be an incidental finding in neuroimaging studies or they may not be accompanied by seizures in patients with various known congenital brain malformations [4]. Although they have been detected in a considerable number of epilepsy patients, the side of MHD is not always related to the side of the EEG focus [1,2,6], raising concerns about the epileptogenicity of these malformations. Interestingly, MHD has also been detected in about 10% of healthy controls [6]. On the other hand, two separate studies have investigated the presence of hippocampal malformations in family members of patients with familial febrile convulsions/mesial TLE [5,11]. The fact that MHD were also present in asymptomatic members lead to the overall conclusion that MHD may be indicative of pre-existing predisposition to seizures, which is modulated by other modifying factors. Disturbance of hippocampal neuronal migration in immature rats lowers the threshold to hyperthermia-induced behavioral seizures and neuronal damage within the hippocampus [12]. The findings in our patient also support the idea that MHD may be epileptogenic and that these patients may benefit from epilepsy surgery, although it is hard to speculate why only one of the hippocampi was epileptogenic and not both. To the best of our knowledge, there is no information in the literature regarding the long term follow up of patients with bilateral isolated MHD who underwent temporal lobectomy for seizure control. Few studies on the other hand, have reported the postoperative prognosis in patients with bilateral hippocampal atrophy and temporal resection, and 52–80% of the patients have been reported to be seizure free or in class I–II according to Engel’s classification [13,14]. To conclude, isolated MHD may be epileptogenic and if all the preoperative work-up suggests that seizures originate from the mesial temporal structures on one side, patients may benefit from resective surgery, i.e. temporal lobectomy with amygdalohippocampectomy, even if the abnormalities are bilateral. References [1] Baulac M, De Crissac N, Hasboun D, Oppenheim C, Adam C, Arzimanoglou A, et al. Hippocampal developmental changes in patients with partial epilepsy: magnetic resonance imaging and clinical aspects. Ann Neurol 1998;44: 223–33.
N. Dericioglu et al. / Clinical Neurology and Neurosurgery 111 (2009) 554–557 [2] Barsi P, Kenez J, Solymosi D, Kulin A, Halasz P, Rasonyi G, et al. Hippocampal malrotation with normal corpus callosum: a new entity? Neuroradiology 2000;42:339–45. [3] Sloviter RS, Kudrimoti HS, Laxer KD, Barbaro NM, Chan S, Hirsch LJ, et al. “Tectonic” hippocampal malformations in patients with temporal lobe epilepsy. Epilepsy Res 2004;59:123–53. [4] Sato N, Hatakeyama S, Shimizu N, Hikima A, Aoki J, Endo K. MR evaluation of the hippocampus in patients with congenital malformations of the brain. AJNR Am J Neuroradiol 2001;22:389–93. [5] Fernandez G, Effenberger O, Vinz B, Steinlein O, Elger CE, Döhring W, et al. Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis. Neurology 1998;50:909–17. [6] Bernasconi N, Kinay D, Andermann F, Antel S, Bernasconi A. Analysis of shape and positioning of the hippocampal formation: an MRI study in patients with partial epilepsy and healthy controls. Brain 2005;128:2442–52. [7] Thom M, Sisodiya SM, Lin WR, Mitchell T, Free SL, Stevens J, et al. Bilateral isolated hippocampal malformation in temporal lobe epilepsy. Neurology 2002;58:1683–6. [8] Kier EL, Kim JH, Fulbright RK, Bronen RA. Embryology of the human fetal hippocampus: MR imaging, anatomy, and histology. AJNR Am J Neuroradiol 1997;18:525–32.
557
[9] Nowakowski RS, Rakic P. The site of origin and route and rate of migration of neurons to the hippocampal region of the rhesus monkey. J Comp Neurol 1981;196:129–54. [10] Amano S, Ihara N, Uemura S, Yokoyama M, Ikeda M, Serikawa T, et al. Development of a novel rat mutant with spontaneous limbic-like seizures. Am J Pathol 1996;149:329–36. [11] Kobayashi E, Li LM, Lopes-Cendes I, Cendes F. Magnetic resonance imaging evidence of hippocampal sclerosis in asymptomatic, first-degree relatives of patients with familial mesial temporal lobe epilepsy. Arch Neurol 2002;59:1891–4. [12] Germano IM, Zhang YF, Sperber EF, Moshe SL. Neuronal migration disorders increase susceptibility to hyperthermia-induced seizures in developing rats. Epilepsia 1996;37:902–10. [13] Li LM, Cendes F, Antel SB, Andermann F, Serles W, Dubeau F, et al. Prognostic value of proton magnetic resonance spectroscopic imaging for surgical outcome in patients with intractable temporal lobe epilepsy and bilateral hippocampal atrophy. Ann Neurol 2000;47(2):195–200. [14] King D, Spencer SS, McCarthy G, Luby M, Spencer DD. Bilateral hippocampal atrophy in medial temporal lobe epilepsy. Epilepsia 1995;36(9):905–10.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Resective surgery is possible in patients with temporal lobe epilepsy due to bilateral isolated hippocampal malformation Nese Dericioglu a,∗ , Kader Karli Oguz b , Figen Soylemezoglu c , Nejat Akalan d , Serap Saygi e a
Hacettepe University, Institute of Neurological Sciences and Psychiatry, Department of Neurology, Sihhiye 06100, Ankara, Turkey Hacettepe University School of Medicine, Department of Radiology, Turkey c Hacettepe University School of Medicine, Department of Pathology, Turkey d Hacettepe University School of Medicine, Department of Neurosurgery, Turkey e Hacettepe University School of Medicine, Department of Neurology, Turkey b
a r t i c l e
i n f o
Article history: Received 20 October 2008 Received in revised form 2 March 2009 Accepted 3 March 2009 Keywords: Temporal lobe epilepsy Bilateral hippocampal malformation Surgery Pathology Prognosis
a b s t r a c t Various hippocampal malformations have been described in the context of widespread cortical malformations in patients with epilepsy. Isolated hippocampal malformations however are very rarely identified on MR imaging studies. Little is known about the epileptogenicity of these malformations and their pathologic appearance. We present a case with severe bilateral hippocampal malformations who underwent right temporal lobectomy due to intractable temporal lobe epilepsy. Postoperative examination of the resected hippocampus revealed abnormal shape of the dentate gyrus and an atypical convolution of the CA1 pyramidal cell-subicular layers. After surgery, the patient has been seizure free. © 2009 Elsevier B.V. All rights reserved.
1. Introduction Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults and is usually accompanied by hippocampal sclerosis (HS). Temporal lobectomy renders most of these patients seizure free, indicating that mesial temporal structures are somehow involved in the pathophysiology of epilepsy. Recently developmental malformations of the hippocampus have been recognized increasingly on magnetic resonance (MR) imaging [1–7] in patients with epilepsy and are not infrequently accompanied by cortical malformations. However isolated hippocampal malformations are extremely rare. Unlike HS, it is not well known to what extent the malformed hippocampus contributes to the generation of seizures. Given that some of the hippocampal structures commonly involved in seizures in HS (e.g. dentate gyrus, CA1, and subiculum) are altered in malformed hippocampi, it is possible that the malformed hippocampus may be involved in seizure generation and/or propagation. So far, very few studies have reported the postoperative outcome in patients with hippocampal malformation [1,3], and outcome is similar to patients with HS [3]. Although MR imaging criteria for the abnormal shape and positioning of the hippocampal formation (HF) have been well described [2,6], the
∗ Corresponding author. Tel.: +90 312 305 1182; fax: +90 312 309 3451. E-mail address: [email protected] (N. Dericioglu). 0303-8467/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2009.03.002
microscopic correlates are less clear [3,7]. Here we present the clinical and laboratory findings of a patient with TLE and severe bilateral isolated malformation of the hippocampi who has been seizure free on medications for 2 years after right temporal lobectomy with amygdalo-hippocampectomy. 2. Case report A 22-year-old female patient was admitted for long term videoEEG monitoring due to intractable seizures that had started at the age of 13. She was the product of an unrelated couple. The prenatal history was normal, however delivery was difficult. Her developmental milestones were normal and at the time of admission she was a university student. One of her cousins also had epilepsy, which could not be further identified. Otherwise her personal and family histories were unremarkable. She had partial seizures with oral automatisms, during which consciousness was preserved. She reported de ja vu prior to some of her seizures that were not controlled with various combinations of carbamazepine (CBZ), phenobarbital, valproate, lamotrigine, levetiracetam (LEV) and topiramate. On admission, she was on CBZ (1000 mg/day) and LEV (1000 mg/day). Three partial seizures were captured within 4 days. Her seizures occurred during wakefulness and the ictal semiologic characteristics were similar in all of them. She had oral automatisms during most of the seizures. At the onset of the second and third
N. Dericioglu et al. / Clinical Neurology and Neurosurgery 111 (2009) 554–557
555
Fig. 1. On coronal T2-weighted imaging (TR/TE: 4800/100 ms) (A and B) and coronal three-dimensional GRE (TR/TE/TI: 2000/4.4/1100 ms, flip angle:10◦ ) (C and D) bilateral severe hippocampal malformation is seen. Please note the presence of disoriented sulci along the inferiomedial temporal lobe.
seizures she hyperventilated and screamed, elevated her left leg and extended both arms. During the seizures she was able to answer all the questions or obeyed the commands. The interictal EEG revealed rare sharp wave paroxysms in the right anterior temporal region. Ictal EEG onset was characterized by irregular 2.5–3 Hz slow waves in the right fronto-temporal region during the first seizure; about 4–5 Hz rhythmic slow waves in the right anterior temporal region during the second seizure and high amplitude rhythmic 2 Hz delta waves in the right fronto-temporal area during the last seizure. After the initial changes, a build-up characterized by 5–7 Hz rhythmic sharp waves in the right temporal region appeared in all of the seizures. MR imaging performed at a 3T imager (Allegra, Siemens, Erlangen, Germany) revealed bilateral malrotation of the hippocampi with accompanying abnormal sulcation along the floor of the medial temporal lobe (Fig. 1A–D). Absence of horizontally located ovoid hippocampi with empty choroid fissures, medial location of the hippocampi, vertically oriented collateral sulci, short parahippocampal gyri and thin collateral white matter were the findings suggesting malrotation of the hippocampi as described by Baulac
et al. in 1998 [1]. Other functional neuro-imaging tests (e.g. PET and SPECT) were not performed. Regarding the neuropsychological findings, several preoperative tests were performed including AVLT, WMS-R, line orientation, Rey-Osterrieth complex figure and digit span. The test results indicated moderate impairment of the right temporal lobe functions, whereas left temporal functions were within normal limits. Based on clinical observation of the seizures and electrophysiologic data the patient underwent right anterior temporal lobectomy with amygdalo-hippocampectomy. The en bloc hippocampal resection was fixed in 10% formalin before routine processing in paraffin. Serial coronal sections 5-m-thick passing through the hippocampal formation were obtained and processed routinely. Care was taken to ensure that all hippocampal sections were cut in a plane perpendicular to the longitudinal axis of the hippocampus and the ones described in the study were from the body of the hippocampus. Sections were stained with hematoxylin and eosin (H&E) and with antisera against NeuN, which revealed an atypical convolution of CA1/subicular neurons (Fig. 2). The dentate gyrus had a very unusual shape, with some finger-like projections of granule cells into the surrounding
556
N. Dericioglu et al. / Clinical Neurology and Neurosurgery 111 (2009) 554–557
Fig. 2. NeuN staining revealed an atypical convolution of CA1 pyramidal neurons/subicular layers without obvious cell loss in the CA subfields. Note the angulated configuration of the dentate gyrus that is misplaced by the atypical indentation of CA1/subiculum layers (asterisk) (sub: subiculum, DG: dentate gyrus).
areas. There was minimal or no cell loss in the dentate hilus, and CA1–CA3 areas, unlike samples of HS. 3. Discussion We present a case with bilateral isolated hippocampal developmental abnormalities who underwent right temporal lobectomy with amygdalo-hippocampectomy due to TLE and has been seizurefree on medications for 2 years. High resolution cranial MR imaging has made it possible to detect subtle brain malformations and hippocampal shape abnormalities have been recognized increasingly during the last years. In different patient series the frequency of MR imaging defined malformations of hippocampal development (MHD) varies between 2.2% and 64% [2,3,6]. The rates seem to be much higher in patients with various malformations of cortical development [4,6]. In a recent study, bilaterality of hippocampal malrotation was reported in 12.5% of 32 cases who had been investigated for presumed epilepsy [2]. There is limited data regarding the neuropathological correlates of MHD in TLE [1,3,7]. In an adult patient with TLE who had bilateral hippocampal abnormalities on MR imaging, Thom et al. reported the autopsy findings of the HFs [7]. Histologic examination revealed that the hilus of the dentate gyrus was more vertical than horizontal on some levels. Complex foldings of CA1 appeared excessively long and serpiginous. There was no evidence of cell loss, dysplasia or gliosis. The dentate granule cell layer was well defined with minimal cell dispersion. In the series by Baulac et al. surgical resection and pathologic description were available for one patient, confirming hippocampal sclerosis in combination with an abnormally folded subiculum [1]. Finally, Sloviter et al. reported the pathological findings of the hippocampus/dentate gyrus in 16 patients with malformations of the HF [3]. The authors reported the presence of an atypical convolution of the CA1 pyramidal cell/subicular layers, similar to ours, and it appeared to invaginate or sometimes bisect the adjacent dentate gyrus. The granule cell layer exhibited unusual morphological features. Immunostaining revealed abnormal dentate gyrus lamination in segments containing the pyramidal cell layer anomaly. Interestingly, none of the hippocampi had abnormal configurations or locations on conventional MR imaging scan.
The MR imaging appearance of the HF in our patient had similarities to those reported by Kier et al. in human fetal brain, roughly corresponding to 18 weeks of gestation [8]. Among cortices, neurons destined for the hippocampal region are perhaps the earliest to be born, however in terms of neuroblast migration and cytoarchitectural maturation, the hippocampal region is late compared with much of the neocortex [9]. By 15–19 weeks, the hippocampus begins to flex over the parahippocampal gyrus, thus forming the hippocampal fissure. Subicular, ammonic, and dentate subfields are readily identifiable. By the end of gestation, the predominantly adultlike cytoarchitectural features of the various hippocampal subfields are present, with only several minor differences. The hippocampus remains qualitatively similar after the ninth postnatal month. The mechanisms resulting in MHD are not well known, but it has been hypothesized that disturbances in mechanical forces with increased brain size and/or specific factors influencing gyrogenesis may be involved. The bilateral MHD in our patient may have resulted from an unidentified insult occurring early in development. It is interesting though that the hippocampal malformations were isolated and not accompanied by other cortical developmental pathologies. That similar pathological findings of the HF without macroscopic malformations of the brain were described earlier by Amano et al. in a novel rat mutant with spontaneous limbic-like seizures [10] also suggests that some kind of genetic mutation may be responsible. It is not known to what extent the malformation represents the epileptogenic tissue, because not all brain malformations are potentially epileptogenic and some may be an incidental finding in neuroimaging studies or they may not be accompanied by seizures in patients with various known congenital brain malformations [4]. Although they have been detected in a considerable number of epilepsy patients, the side of MHD is not always related to the side of the EEG focus [1,2,6], raising concerns about the epileptogenicity of these malformations. Interestingly, MHD has also been detected in about 10% of healthy controls [6]. On the other hand, two separate studies have investigated the presence of hippocampal malformations in family members of patients with familial febrile convulsions/mesial TLE [5,11]. The fact that MHD were also present in asymptomatic members lead to the overall conclusion that MHD may be indicative of pre-existing predisposition to seizures, which is modulated by other modifying factors. Disturbance of hippocampal neuronal migration in immature rats lowers the threshold to hyperthermia-induced behavioral seizures and neuronal damage within the hippocampus [12]. The findings in our patient also support the idea that MHD may be epileptogenic and that these patients may benefit from epilepsy surgery, although it is hard to speculate why only one of the hippocampi was epileptogenic and not both. To the best of our knowledge, there is no information in the literature regarding the long term follow up of patients with bilateral isolated MHD who underwent temporal lobectomy for seizure control. Few studies on the other hand, have reported the postoperative prognosis in patients with bilateral hippocampal atrophy and temporal resection, and 52–80% of the patients have been reported to be seizure free or in class I–II according to Engel’s classification [13,14]. To conclude, isolated MHD may be epileptogenic and if all the preoperative work-up suggests that seizures originate from the mesial temporal structures on one side, patients may benefit from resective surgery, i.e. temporal lobectomy with amygdalohippocampectomy, even if the abnormalities are bilateral. References [1] Baulac M, De Crissac N, Hasboun D, Oppenheim C, Adam C, Arzimanoglou A, et al. Hippocampal developmental changes in patients with partial epilepsy: magnetic resonance imaging and clinical aspects. Ann Neurol 1998;44: 223–33.
N. Dericioglu et al. / Clinical Neurology and Neurosurgery 111 (2009) 554–557 [2] Barsi P, Kenez J, Solymosi D, Kulin A, Halasz P, Rasonyi G, et al. Hippocampal malrotation with normal corpus callosum: a new entity? Neuroradiology 2000;42:339–45. [3] Sloviter RS, Kudrimoti HS, Laxer KD, Barbaro NM, Chan S, Hirsch LJ, et al. “Tectonic” hippocampal malformations in patients with temporal lobe epilepsy. Epilepsy Res 2004;59:123–53. [4] Sato N, Hatakeyama S, Shimizu N, Hikima A, Aoki J, Endo K. MR evaluation of the hippocampus in patients with congenital malformations of the brain. AJNR Am J Neuroradiol 2001;22:389–93. [5] Fernandez G, Effenberger O, Vinz B, Steinlein O, Elger CE, Döhring W, et al. Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis. Neurology 1998;50:909–17. [6] Bernasconi N, Kinay D, Andermann F, Antel S, Bernasconi A. Analysis of shape and positioning of the hippocampal formation: an MRI study in patients with partial epilepsy and healthy controls. Brain 2005;128:2442–52. [7] Thom M, Sisodiya SM, Lin WR, Mitchell T, Free SL, Stevens J, et al. Bilateral isolated hippocampal malformation in temporal lobe epilepsy. Neurology 2002;58:1683–6. [8] Kier EL, Kim JH, Fulbright RK, Bronen RA. Embryology of the human fetal hippocampus: MR imaging, anatomy, and histology. AJNR Am J Neuroradiol 1997;18:525–32.
557
[9] Nowakowski RS, Rakic P. The site of origin and route and rate of migration of neurons to the hippocampal region of the rhesus monkey. J Comp Neurol 1981;196:129–54. [10] Amano S, Ihara N, Uemura S, Yokoyama M, Ikeda M, Serikawa T, et al. Development of a novel rat mutant with spontaneous limbic-like seizures. Am J Pathol 1996;149:329–36. [11] Kobayashi E, Li LM, Lopes-Cendes I, Cendes F. Magnetic resonance imaging evidence of hippocampal sclerosis in asymptomatic, first-degree relatives of patients with familial mesial temporal lobe epilepsy. Arch Neurol 2002;59:1891–4. [12] Germano IM, Zhang YF, Sperber EF, Moshe SL. Neuronal migration disorders increase susceptibility to hyperthermia-induced seizures in developing rats. Epilepsia 1996;37:902–10. [13] Li LM, Cendes F, Antel SB, Andermann F, Serles W, Dubeau F, et al. Prognostic value of proton magnetic resonance spectroscopic imaging for surgical outcome in patients with intractable temporal lobe epilepsy and bilateral hippocampal atrophy. Ann Neurol 2000;47(2):195–200. [14] King D, Spencer SS, McCarthy G, Luby M, Spencer DD. Bilateral hippocampal atrophy in medial temporal lobe epilepsy. Epilepsia 1995;36(9):905–10.