Cavernous Malformations and Seizures: Lesionectomy or Epilepsy Surgery?

15
Cavernous Malformations and Seizures: Lesionectomy or Epilepsy Surgery?


Giovanni Broggi, Paolo Ferroli, and Angelo Franzini


Cavernous malformations (CMs) are an increasingly recognized cause of partial epilepsy. These benign, mulberry-like vascular lesions may occur at any site within the CNS, as well as in other organs such as the liver, bone, or skin. Histologically, they consist of ectatic, endothelium-lined channels without mural muscular or elastic fibers within a matrix of collagenous tissue lacking any neuronal elements. Typically, although not invariably, gliosis and hemosiderin deposition can be found in the surrounding neural parenchyma.1 Supratentorial CMs present with epileptic seizures, less often with hemorrhage or with signs and symptoms of space-occupying lesions.26 The diagnostic incidence of CMs has dramatically increased in the magnetic resonance imaging (MRI) era. It is not uncommon to see patients with incidentally diagnosed, asymptomatic CMs.79


Epileptic seizures caused by CMs are often medically refractory10,11 as is often the case for partial seizures secondary to other space-occupying lesions.12,13 Even in patients who present with seizures as the first clinical manifestation, MRI often shows the presence of microhemorrhages. The presence of microhemorrhages in patients with CMs who present with seizures at the first clinical manifestation has been confirmed by postoperative histologic analysis.8,9,14 Epileptic seizures are thought to be the consequence of hemosiderin deposits or the presence of gliotic scars secondary to the microhemorrhages.14,15 Surgical treatment of CMs presenting with seizures is usually recommended, not only to prevent future bleeds but also to prevent future seizures.16 However, surgical indications and optimum management of CMs causing epilepsy still remain controversial.11,1624 In cases of intractable epilepsy with concordant clinical, electrophysiologic, and neuroimaging findings, the indication for surgery is clear. There are no accepted guidelines for the management of patients with CMs and recent onset of seizures or with medically controlled seizures. The best surgical strategy in patients with CMs presenting with seizures (i.e., simple lesionectomy versus “epilepsy surgery”), is also debated.


image Surgical Treatment at Instituto Nazionale Neurologico Carlo Besta


Of 191 patients (111 men, 80 women) with intraparenchymal hemispheric CMs who underwent surgical treatment at our institute between 1988 and 2003, 163 (85.3%) presented with seizures. The mean age at the time of surgery was 33.4 ± 14.2 years (range, 17 to 63 years). The mean duration of illness was 4.5 ± 7.6 years (range, 15 days to 43 years). Ninety-nine (60.7%) patients had a history of chronic epilepsy and a longer mean duration of illness (10.2 ± 9.1 years). Sixty-four (39.3%) patients had only single or sporadic seizures, and an immediate diagnosis of CM and surgical treatment, so that the mean duration of illness was much shorter (1.2 ± 1.7 years).


Preoperative Assessment


In patients with chronic epilepsy, the aim of the preoperative investigation was to identify a possible correlation between electroclinical and anatomic data. Data from detailed clinical histories, neurologic examinations, MR images, and scalp electroencephalograms (EEGs) were collected and examined. Seizures were divided into simple partial, complex partial, and secondary generalized seizures according to the International League against Epilepsy classification. Scalp EEGs with hyperventilation and photic stimulation are obtained by use of 16- or 18-channel bipolar recordings according to the International 10–20 system. In some cases, sleeping and waking EEGs were recorded. Only a few patients required video-EEG recording. EEGs were classified as normal; nonspecific, when nonfocal waves were present; or focal, when slow waves, sharp waves, spikes, rapid activity, or any combination of these abnormalities were restricted to one or two adjacent channels.


All patients underwent preoperative MRI (0.5 or 1.5 T). Magnetic resonance images consisted of multiplanar spin echo sequences using T1- and T2-weighted images and, also, in most patients, gradient echo T2-weighted images. Functional MRI data were collected in patients with CMs in eloquent areas treated more recently. When a correlation between cavernoma location and electroclinical data was found, patients underwent lesionectomy without any other investigation. Only patients with incongruent data (multifocal seizures, multiple cavernomas, suspected dual pathology, etc.) were considered candidates for further invasive studies.


Surgical Technique


When lesionectomy alone was performed, this was accomplished by a minimally invasive transsulcal approach under high magnification. Before neuronavigation became available, the entrance sulcus was chosen with the help of a stereotactic frame. A guidance catheter was inserted to guide the surgeon only when approaching deep lesions. Frameless image-guidance with different neuronavigation systems has been employed since 1995. Functional MRI data fused with conventional neuronavigation MR images and direct cortical mapping data collected during awake surgery were used for surgical planning in case of eloquent location. Short linear skin incisions (6 to 8 cm) were generally used. The diameter of the craniotomy (2 to 4 cm) was chosen according to the amplitude of the arachnoidal incision planned to reach the lesion. The larger and deeper the lesion is, the longer the arachnoidal incision. This strategy was adopted to avoid any traction at the edges of the arachnoidal incision and to minimize compression on the cortical surface exposed within the sulcus. Retractors were generally avoided; when used, care was taken to keep them loose. The cortical surface within the sulcus is protected with unsticky cottonoids. Sharp incision of the superficial arachnoidal layer and underlying arachnoidal bands under high magnification is used (the tip of a 22-gauge needle used as a knife and microscissors). Any damage to the pial surface of the surgical corridor to the lesion is carefully avoided, until the pial surface covering the lesion is reached and incised using bipolar low-current coagulation. Particular care is taken to avoid damage to the vessels at the bottom of the sulcus. The surgical strategy is lesionectomy, limiting the removal to the CM and covering cortex, as clear evidence is lacking that better outcomes result from removing the hemosiderin-stained gliotic perilesional tissue.


Postoperative Follow-up


Postoperative follow-up included similar clinical, neuroradiologic, and electroencephalographic examinations used in the preoperative assessment. Antiepileptic drugs in patients with seizures were withdrawn after at least a 1-year seizure-free follow-up period. Three patients required reoperation because of recurrent seizures due to residual CM (Fig. 15-1). The mean duration of follow-up was 48 months (range, 0.5 to 14 years).


image

Figure 15-1 Surgical plan and intraoperative view of a case of residual cavernoma (arrow and dotted line) that required surgery for seizure persistency. After repeated surgery, the patient was seizure-free.


Clinical History, Preoperative Neurologic Examination, and Cavernous Malformation Location


None of the patients had any risk factor for epilepsy. Preoperative neurologic examination was within normal limits in 139 patients. The other 24 had focal neurologic signs. In one patient who had suffered seizures since the age of 13, mild hemiparesis had become apparent in the early months of life: this was believed to be secondary to the presence of a giant motor strip CM. Two patients suffered intracerebral bleeding after having presented with seizures.


Mesiotemporal, temporolateral, or insular cavernomas were more commonly observed in patients with chronic epilepsy (mesiotemporal, 19.2%; neocortical temporal, 34.3%) than in those with occasional seizures (mesiotemporal, 7.8%; neocortical temporal, 17.2%); the most frequent location in this latter group being the frontal region (57.6%, versus 19% of the patients with chronic epilepsy). The CM was subcortical in 52.1%, cortical in 19.6%, and corticosubcortical in 12.3% of cases. There were no significant differences in cortical or subcortical location in patients with chronic epilepsy when compared with those with occasional seizures.


The size of the lesions ranged from 0.5 to 4 cm, although in one patient, the CM was unusually large (6 cm) and mimicked a hemorrhagic tumor. The MRI findings reproduced the typical picture of CMs previously reported.9,19 The core of the malformation was commonly found to have a high signal in both T1- and T2-weighted images, thus indicating the presence of extracellular methemoglobin. In some patients, mixed areas of decreased and increased intensity were observed, the result either of different stages of hemorrhage or of interspersed areas of calcification. In all of the patients, T2-weighted images revealed peripheral marginal or ring-like hypointensity caused by hemosiderin drift. Eleven patients had evident radiologic signs of previous bleeding with intraparenchymal hematoma, for which three of them had undergone surgery in the years preceding the excision of the CM. An associated developmental venous anomaly was commonly observed. Mass effects and surrounding edema were found in 14 patients. Twenty-two patients had multiple CMs (13.5%). In the 99 patients with chronic epilepsy, seizures were completely controlled by antiepileptic drugs in only 36 patients.


Thirty-seven of the 163 patients had exclusively generalized tonic-clonic seizures. Twenty-two patients had usually generalized tonic-clonic seizures with focal onset. Simple partial seizures were reported in 64 patients and partial complex seizures in 35 patients, with simple onset in 11. In two patients with multiple CMs, two different types of seizures were reported. The results were normal or nonspecific in 40.9% of those who had waking EEGs; 61.1% of the patients also had sleep EEGs, which were normal in 45.4% and revealed focal abnormalities in 54.6%. Overall focal electroencephalographic abnormalities were found in 68.2% of the total patient population.


Epilepsy Outcome after Lesionectomy


Among the 99 patients with chronic epilepsy, 68 (68.7%) are completely seizure-free (20 of 68 [29.4%] still under AEDs [antiepileptic drugs]), 10 (10.1%) have only sporadic seizures, and 17 (17.1%) still have seizures despite surgery and therapy. Four patients were lost to follow-up. In patients with preoperative drug-resistant epilepsy, only 60% were seizure free at follow-up. As previously mentioned, three patients required reoperation because of seizures due to residual CM (Fig. 15-1). Sixty-three of the 64 (98.4%) patients without chronic epilepsy (single or sporadic seizures) were completely seizure free (28% still waiting for definitive withdrawal of AEDs, which usually occurs 2 years after surgery). One patient was lost to follow-up. A longer clinical history of chronic epilepsy was found to be related to a poorer prognosis. No clear correlation between CM location and outcome could be found even though there was a trend for mesiotemporal CMs to have poorer prognosis in terms of seizure control.


Mortality and Morbidity


Postoperative focal neurologic signs (sensorimotor defects and homonymous hemi- or quadrantopia) appeared in 12% of patients. Most of these signs were transient and had completely disappeared or were greatly reduced at subsequent clinical examinations. Only in three (1.8%) patients was a partial residual deficit found at long-term follow-up. These consist of slight hand paresis in a patient with a CM under the motor hand area; right inferior limb paresis with a slight gait impairment in a patient with a CM of the mesial prerolandic cortex; and hemianopsia in a patient harboring a CM in the depth of the calcarine scissure who required emergency surgery for evacuation of a postoperative hematoma. There was no mortality. Postoperative MRI was available in 122 cases and showed a complete CM resection in all patients (in three after repeated surgery). Hospital stay and duration of surgery progressively shortened as image-guided minimally invasive techniques became available. Mean surgery duration in the last 50 cases was around 2 hours and the mean hospital stay 4 days.


image Epileptogenesis in Patients with Cavernous Malformations


The underlying mechanisms causing seizures in patients with CMs are complex and still not completely understood. Given the lack of intralesional brain tissue, CMs per se are clearly not epileptogenic.25 Furthermore, the mass effect does not explain the high epileptogenicity of this vascular malformation. Other lesions of larger size such as diffuse growing malignant tumors are less commonly associated with medically refractory epilepsy,26,27 and epileptogenic mechanisms seem to be different.28 Awad and Robinson compared the seizure incidence in patients harboring a CM with that of patients with arteriovenous malformations (AVMs) or gliomas and found an incidence of 50 to 70% in cavernomas, 20 to 40% in AVMs, and 10 to 30% in gliomas.29 In our series, 99 of 163 (60.7%) patients operated on for a CM were affected by chronic epilepsy. Seventy-seven of 99 (77.7%) were drug resistant. Del Curling et al. estimated the risk of developing seizures at 1.51% per person/year and 2.48% per lesion/year for those with multiple lesions.30 According to Cohen et al., 41 to 59% of symptomatic CMs will present with seizures,31 and around 4% of refractory partial epilepsies are thought to be symptomatic of CMs.32


Williamson et al. recently reported the results of intracellular recording from neurons adjacent to intracerebral neoplasms and CMs.28 Neurons adjacent to CMs were found to have a greater propensity to show large, complex, spontaneous synaptic events than neurons adjacent to tumors. Both spontaneous excitatory and inhibitory events were recorded. Neurons neighboring CMs displayed more excitable responses to synaptic stimulation, with multiple action potentials riding on prolonged excitatory postsynaptic potentials being evoked (71% vs. 32% of neurons from the tumor group). In studies using hippocampal tissue, these authors noted a similar pattern of spontaneous activity in tissue adjacent to CAs, suggesting that a common synaptic mechanism should be hypothesized for both neocortical and hippocampal CMs. The prevalence of epileptiform responses appeared to correlate only with the proximity of the lesion.


The underlying cause for CM epileptogenicity is thought to be the presence of chronic, clinically silent microhemorrhages25,33 secondary to fragility of the capillary sinusoidal wall and lack of tight junctions. This results in deposition of iron-containing blood breakdown products such as hemosiderin, a probable degradation product of ferritin, as well as hemin, a globin breakdown product, in the adjacent brain tissue. Iron salts are proven potent epileptogenic agents when applied on the rat cortex.32,34,35 Iron may generate epilepsy by different mechanisms. As an electron donor, iron is implicated in the production of free radicals and lipid peroxides, which interact with receptor activity, calcium channels, cellular transport proteins, intracellular second messengers, and neurotransmitter (glutamate and aspartate)-mediated excitotoxicity.33,36,37 Von Essen et al. found a marked increase in the levels of serine (fivefold), glycine (10-fold) and ethanolamine (20-fold) in the peripheral zone of cerebral CMs.38 In addition, iron deposition seems to inhibit glutamate uptake. Such biochemical abnormalities in the marginal zone of CMs may cause excessive activation of excitatory transmission. Studies using a ferrous chloride model of epilepsy demonstrated that gliosis and neuronal loss can occur39 presumably because of the generation of free radicals and subsequent lipid peroxidation.40,41 Iron-triggered cellular alterations are more likely and more significant the longer the duration of epilepsy. As a consequence, the tissue adjacent to CMs becomes increasingly epileptogenic.42 This can explain why the longer the history of epilepsy, the poorer are the results of pure lesionectomy.


Iron-laden epileptogenic tissue may cause independent secondary epileptogenic foci in experimental animals by kindling. However, it is controversial whether or not such secondary foci are found in humans. One indicator of secondary epileptogenesis in humans is the finding of dual pathology, that is, hippocampal neuronal cell loss in some patients harboring extrahippocampal lesions such as brain tumors, cortical dysgenesis, or vascular malformation.27,4345 In patients with CMs, dual pathology has rarely been found.28,43,46 In these patients, lesionectomy did not result in seizure control, and subsequent resection of the mesial temporal lobe structures became necessary to achieve satisfactory seizure outcome.43,46,47 In summary, as far as epileptogenesis of CMs is concerned, it can be speculated that the hemosiderin deposition near CMs results in impaired glutamate uptake as well as injury-induced synaptic reorganization, which may subsequently allow neuronal hypersynchronization in focal regions. This can then propagate activity to more distant regions.


image Indications for Surgical Treatment


Surgical indication should arise from the comparison between the risks of surgery and the risks related to the natural history of these lesions. As far as CMs are concerned, there has been in the recent past a growing tendency to recommend resection of supratentorial CMs for the following reasons:



  • Risk of bleeding: Supratentorial CMs, although rarely, may cause large intracerebral hematomas and irreversible neurologic deficits.48 The estimated risk of bleeding for supratentorial CMs is ~0.7% per patient per year.49
  • Risk of CM growth: CMs have been recently recognized to be dynamic lesions that may arise after birth and grow.50
  • Risk of developing seizures: This risk has been estimated to be as high as 1.5% per person per year.30
  • Low surgical risk and effectiveness of CM removal in preventing bleedings and seizures: Minimally invasive, image-guided supratentorial CM resection has been shown to be safe and effective even in eloquent areas (in our series: 1.8% permanent morbidity, no mortality, 98.4% of cases seizure-free when patients undergoing surgery after one or sporadic seizures are considered, 98% incidence of complete removal after surgery).

It is our policy to recommend surgery for all symptomatic supratentorial CMs.


image Lesionectomy or Epilepsy Surgery?


Many retrospective studies reported a good outcome after CM resection in patients with seizures (Table 15-1). Seizure outcome of lesionectomy alone is excellent with improvement of seizure control in 92% of cases, amounting to abolishment of seizures in 84%.51 No data are available to clearly demonstrate a different outcome if lesionectomy includes the perilesional hemosiderin-stained tissue. In our opinion, there is no significant difference in seizure outcome whether lesionectomy alone or a “seizure operation” is performed. Literature data suggest that seizure history and length of clinical history are the main prognostic factor. This confirms what Olivecrona and Riives stated as early as 1948: “… the prognosis of epilepsy is best in the case of the younger person with a short history of epilepsy, while in cases of inveterate disease with a long history of epilepsy the outcome is poor.” In our series, all patients who underwent lesionectomy after the first seizure or who presented only with sporadic seizures remained seizure-free at long-term follow-up, whereas 40% of patients with a clinical history of chronic epilepsy (often drug-resistant) still had seizures after lesionectomy. Early lesionectomy seems therefore to be the best way to avoid the development of chronic epilepsy. The fact that the duration of epilepsy at time of surgery has a negative influence on seizure outcome underscores the importance of early CM resection. It is our policy to recommend surgery after the first seizure. What to do when a chronic, often drug-resistant epilepsy develops still remains under debate. Lesionectomy obviously holds the greater theoretical benefit of removing the smallest amount of nonpathologic cerebral parenchyma by means of a straightforward, low-risk, minimally invasive surgery, requiring a few days of hospitalization. Such a minimal resection, however, may not provide the desired complete relief from seizures. Conversely, localization and removal of the epileptogenic zone may provide a higher rate of cure than lesionectomy alone. The price of real epilepsy surgery may include invasive electroclinical investigations such as stereoelectroencephalography, corticography, and strips recording of brain parenchyma outside the lesion. The surgical resection may be tailored according to electroclinical data and may result in a considerably wider resection than pure lesionectomy. In our series, lesionectomy alone allowed for the control of seizures in 60% of epileptic patients, avoiding potential complication of invasive studies, subsequent resection of brain parenchyma, along with added time and equipment costs. These considerations led in our institute to the institution of a two-step surgery for CM-related chronic epilepsy. Patients and families are fully informed, and during the first operation only the lesion is removed. Twelve to 24 months later, if drug-resistant seizures are still present (despite MRI demonstration of radical resection), second surgery is performed with the goal of removing some of the surrounding hemo-siderin-stained brain often with the guidance of invasive electrophysiologic data.













































Table 15-1 Seizure Outcome after Lesionectomy in Recent Patients’ Series with More Than 10 Reported Cases
Author (Year) Number of Cases Outcome
Lonjon et al. (1993)3 16 14/16 seizure-free 2/16 improved
Giulioni et al. (1995)16 11 Improved seizure control in 100% Seizure-free without therapy: 18%
Zevgaridis et al. (1996)23 168 88.3% seizure-free 6.5% marked reduction in seizure frequency
Braun et al. (1996)17 14 10/14 complete relief 2/14 improved
Cappabianca et al. (1997)18 35 Less than five preoperative seizures:100% seizure-free More than five preoperative seizures: 62.5% seizure-free
Moran et al. (1999)51 33 Improvement in seizures in 92%
Mahla et al. (1999)4 31 Alleviation of epilepsy: 21/31 Seizure-free without medication: 4/31
Current series (2004) 163 Preoperative chronic epilepsy: 68/99 (68.7%) seizure-free Preoperative only sporadic seizures: 63/64 (98.4%) seizure-free

 


References


1. Russel DS, Rubinstein LJ. Tumours and hamartomas of the blood vessels. In: The Pathology of Tumours of the Nervous System. Fifth ed. London: Arnold; 1989:727–790


2. Giombini S, Morello G. Cavernous angiomas of the brain: account of fourteen personal cases and review of the literature. Acta Neurochir (Wien) 1978;40:61–82


3. Lonjon M, Roche JL, George B, et al. Intracranial cavernoma. 30 cases. Presse Med 1993;22(21):990–994


4. Mahla K, Rizk T, Fischer C, Belliard H, Vallee B, Fischer G. Intracranial cavernoma. Surgical results of 47 cases. Neurochirurgie 1999;45(4): 286–292


5. Vaquero J, Salazar J, Martinez R, Martinez P, Bravo G. Cavernomas of the central nervous system: clinical syndromes, CT scan diagnosis, and prognosis after surgical treatment in 25 cases. Acta Neurochir (Wien) 1987;85:29–33


6. Voigt K, Yasargil MG. Cerebral cavernous hemangiomas or cavernomas: incidence, pathology, localization, diagnosis, clinical features and treatment. Review of the literature and report of an unusual case. Neurochirurgia (Stuttg) 1976;19:59–68


7. Gomori JM, Grossman RI, Goldberg HI, Hackney DB, Zimmerman RA, Bilaniuk LT. Occult cerebral vascular malformations: high-field MR imaging. Radiology 1986;158:707–713


8. Requena I, Arias M, Lopez-Ibor L, et al. Cavernomas of the central nervous system: clinical and neuroimaging manifestations in 47 patients. J Neurol Neurosurg Psychiatry 1991;54:590–594


9. Vielvoye GJ, Pijl MEJ. Magnetic resonance imaging of the so-called cerebral cryptic angiomas. Clin Neurol Neurosurg 1992;94(Suppl): S171-S175


10. Robinson JR, Awad IA, Little JR. Natural history of the cavernous angioma. J Neurosurg 1991;75:709–714


11. Rougier A, Castel JP, Cohadon F. Les différentes modalités de traitement des cavernomes hémisphériques. Neurochirurgie 1989;35:115–119


12. Awad IA, Rosenfeld R, Ahl J, Hahn JF, Lueders HO. Intractable epilepsy and structural lesions of the brain. Epilepsia 1991;32:179–186


13. Cascino GD, Boon PAYM, Fish DR. Surgically remediable lesional syndromes. In: Lueders HO, ed. Epilepsy Surgery. New York, NY: Raven Press; 1992:77–86


14. Lobato RD, Perez C, Rivas JJ, Cordobes F. Clinical, radiological, and pathological spectrum of angiographically occult intracranial vascular malformations. J Neurosurg 1988;68:518–531


15. Kraemer DL, Awad IA. Vascular malformations and epilepsy: clinical considerations and basic mechanisms. Epilepsia 1994;35(Suppl 6): S30-S43


16. Giulioni M, Acciarri N, Padovani R, Galassi E. Results of surgery in children with cerebral cavernous angiomas causing epilepsy. Br J Neurosurg 1995;9(2):135–141


17. Braun V, Antoniadis G, Rath S, Richter HP. Cavernoma. Indications for surgical removal and outcome. Nervenarzt 1996;67(4):301–305


18. Cappabianca P, Alfieri A, Maiuri F, Mariniello G, Cirillo S, de Divitiis E. Supratentorial cavernous malformations and epilepsy: seizure outcome after lesionectomy on a series of 35 patients. Clin Neurol Neurosurg 1997;99(3):179–183


19. Churchyard A, Khangure M, Grainger K. Cerebral cavernous angioma. A potentially benign condition? Successful treatment in 16 cases. J Neurol Neurosurg Psychiatry 1992;55:1040–1045


20. Kahane P, Munari C, Hoffmann D, et al. Approche chirurgicale multi-modale des angiomes caverneux èpilèptogenes. Epilepsies. 1994;6: 113–130


21. Simard JM, Garcia-Bengochea F, Ballinger WE, Mickle JP, Quisling RG. Cavernous angioma: a review of 126 collected and 12 new clinical cases. Neurosurgery 1986;18:162–172


22. Steiger HJ, Markwalder RV, Reulen HJ. Y a-t-il une relation entre manifestation clinique et l’image pathologique des cavernomes cérébraux? Neurochirurgie 1989;35:84–88


23. Zevgaridis D, van Velthoven V, Ebeling U, Reulen HJ. Seizure control following surgery in supratentorial cavernous malformations: a retrospective study in 77 patients. Acta Neurochir (Wien) 1996;138(6):672–677


24. Stefan H, Hammen T. Cavernous haemangiomas, epilepsy and treatment strategies. Acta Neurol Scand 2004;110:393–397


25. Tasker JG, Hoffman NW, Kim YI, Fisher RS, Peacock WJ, Dudek FE. Electrical properties of neocortical neurons in slices from children with intractable epilepsy. J Neurophysiol 1996;75:931–939


26. Otten P, Pizzolato GP, Rilliet B, et al. 131 cases of cavernous angioma of the CNS, discovered by retrospective analysis of 24.535 autopsies. Neurochirurgie 1989;35(2):128–131


27. Schramm J, Kral T, Grunwald T, et al. Surgical treatment for neocortical temporal lobe epilepsy: clinical and surgical aspects and seizure outcome. J Neurosurg 2001;94:33–42


28. Williamson A, Patrylo RP. Sunghoon Lee, Spencer DD. Physiology of human neurons adjacent to cavernous malformations and tumors. Epilepsia 2003;44:1413–1419


29. Awad IA, Robinson JR. In: Awad IA, Barrow DL, eds. Cavernous Malformations. Park Ridge, IL: AANS; 1993:49–63


30. Del Curling O Jr, Kelly DL Jr, Elster AD, Craven TE. An analysis of the natural history of cavernous angiomas. J Neurosurg 1991;75:702–708


31. Cohen DS, Zubay GP, Goodman RR. Seizure outcome after lesionectomy for cavernous malformations. J Neurosurg 1995;83:237–242


32. Ryvlin P, Mauguiere F, Sindou M, Froment JC, Cinotti L. Interictal cerebral metabolism and epilepsy in cavernous angiomas. Brain 1995;118: 677–687


33. Robinson JR Jr, Awad IA, Masaryk TJ, Estes ML. Pathological heterogeneity of angiographically occult vascular malformations of the brain. Neurosurgery 1993;33:547–555


34. Steiger HJ, Markwalder TM, Reulen HJ. Clinicopathological relations of cerebral cavernous angiomas: observations in eleven cases. Neurosurgery 1987;21:879–884


35. Willmore LJ, Sypert GW, Munson JV, Hurd RW. Chronic focal epileptiform discharge induced by injection of iron into rat and cat cortex. Science 1978;200:1501–1503


36. Singh R, Pathak DN. Lipid peroxidation and glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, and glucose-6-phosphate dehydrogenase activities in FeCl3-induced epileptogenic foci in the rat brain. Epilepsia 1990;31:15–26


37. Vives KP, Awad IA. Overview. Vascular causes of epilepsy. In: Kotagal P, Luders H, eds. The Epilepsies: Etiologies and Prevention. New York, NY: Academic Press; 1999:371–383


38. Von Essen C, Rydenhag B, Nyström B, Mozzi R, van Gelder N, Hamberger A. High levels of glycine and serine as a cause of the seizure symptoms of cavernous angiomas? J Neurochem 1996;67:260–264


39. Willmore LJ, Triggs WJ. Iron-induced lipid peroxidation and brain injury responses. Int J Dev Neurosci 1991;9:175–180


40. Kabuto H, Yokoi I, Ogawa N. Melatonin inhibits iron-induced epileptic discharges in rats by suppressing peroxidation. Epilepsia 1998;39: 237–243


41. Willmore LJ. Post-traumatic epilepsy: cellular mechanisms and implication for treatment. Epilepsia 1990;31(Suppl 3):S67-S73


42. Kohling R, Qu M, Zilles K, Speckman EJ. Current-source-density profiles associated with sharp waves in human epileptic neocortical tissue. Neuroscience 1999;94:1039–1050


43. Beaumont A, Whittle IR. The pathogenesis of tumour associated epilepsy. Acta Neurochir (Wien) 2000;142:1–15


44. Spencer DD, Spencer SS. Hippocampal resection and the use of human tissue in defining temporal lobe epilepsy syndromes. Hippocampus 1994;4:243–249


45. Wolf HK, Wiestler OD. Surgical pathology of chronic epileptic seizures disorders. Brain Pathol 1993;3:371–380


46. Bartolomei JC, Christopher S, Vives K, Spencer DD, Pierpmeier JM. Low-grade gliomas of chronic epilepsy: a distinct clinical and pathological entity. J Neurooncol 1997;34:79–84


47. Gunel M, Laurans MS, Shin D, et al. KRIT1, a gene mutated in cerebral cavernous malformation, encodes a microtubule-associated protein. Proc Natl Acad Sci U S A 2002;99:10677–10682


48. Turjman F, Arteaga C, Tavernier T, et al. Haemorrhagic complications of intracerebral cavernomas: Value of MRI. J Neuroradiol 1992;19:107–117


49. Moriarity JL, Wetzel M, Clatterbuck RE, et al. The natural history of cavernous malformations: a prospective study of 68 patients. Neurosurgery 1999;44:1166–1173


50. Pozzati E, Giuliani G, Nuzzo G, Poppi M. The growth of cerebral cavernous angiomas. Neurosurgery 1989;25:92–97


51. Moran NF, Fish DR, Kitchen N, Shorvon S, Kendall BE, Stevens JM. Supratentorial cavernous haemangiomas and epilepsy: a review of the literature and case series. J Neurol Neurosurg Psychiatry 1999;66:561–568


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Jul 16, 2016 | Posted by in NEUROLOGY | Comments Off on Cavernous Malformations and Seizures: Lesionectomy or Epilepsy Surgery?

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