Surgical treatment for temporal lobe epilepsy with preservation of postoperative memory function]

Temporal lobe epilepsy is frequently drug-resistant in adult epilepsy. However, its surgical treatment is very effective and about 70% of operated patients become seizure-free. As preoperative evaluation, analysis of seizure characteristics, scalp EEG with sphenoidal lead, and neuroimaging are most important. When these noninvasive examinations are concordant in focus localization, surgical treatment without prolonged recording by intracranial electrodes become feasible. In spite of good seizure outcome after temporal lobectomy, postoperative impairment of verbal memory has remained to be a long-standing problem. To cope with this ominous complication, we developed a new surgical method of hippocampal transection, based on the principle of multiple subpial transection (MST). Placing a small corticotomy on the anterior part of superior temporal gyrus, the inferior ventricle is opened through suctioning the temporal stem. Intraoperative electrocorticography (ECoG) is recorded over the hippocampus. After the extent of the epileptic area is determined, the alveus is cut with microscissors and the pyramidal layer is transected in parallel with neuronal fibers by a specially designed ring transector. With this procedure, epileptic discharges from the hippocampus can be completely abolished. In all 7 cases undergoing left hippocampal transection, postoperative verbal memory was preserved with excellent seizure outcome.     

伴海马硬化的颞叶癫痫患者的临床特点及手术治疗

目的探讨颞叶癫痫海马硬化的临床特点及手术治疗的效果。方法伴海马硬化的颞叶癫痫患者18例,其中男10例,女8例;年龄12~37岁,病程3~10年。癫痫复杂部分性发作10例,部分性发作继发全身性发作2例,全身强直-痉挛性发作6例。结合患者的临床表现、MRI检查和视频脑电图(V-EEG)监测结果,对这18例患者行前颞叶切除术(包括大部分海马和杏仁核)。结果所有患者术中皮层和深部电极脑电图均发现颞叶皮层海马、杏仁核有异常放电,术后病理检查均证实海马硬化的诊断。术后18例患者均出现发热,但经过抗炎、腰椎穿刺及支持治疗后渐好转。术后1年以上的随访发现16例癫痫发作完全消失,2例术后较术前显著改善,仅偶有癫痫发作,但均长期服用抗癫痫药物。结论对于颞叶癫痫伴有海马硬化的患者,如果同时脑电图又发现有同侧颞叶痫样放电,则可以考虑行该侧前颞叶切除术(包括大部分海马和杏仁核),若手术切除彻底,其术后疗效也较满意。     

A correlative study between hippocampal atrophy quantified by tomo-pneumoencephalography and epileptogenic focus in temporal lobe epilepsy

It appeared certain that we can quantify the rate of hippocampal atrophy by utilizing the sagittal cuts in tomo-pneumoencephalography. This is a reliable method to infer the side of the epileptogenic focus in temporal lobe epilepsy since a close correlation was disclosed between the side with more atrophic features of the hippocampus and that of the epileptogenic focus explored by depth EEG, in particular, in the mesial temporal focus group. On the other hand, it seems to be plausible that the hippocampal atrophy could be secondarily induced by epileptic discharges in the lateral temporal group. Namely, controversies dealing with the casual relationship of hippocampal atrophy should be discussed based on the epileptogenic focus localization in temporal lobe epilepsy.     

Loss of recent memory after bilateral hippocampal lesions. 1957

Bilateral medial temporal lobe resection in man results in a persistent impairment of recent memory whenever the removal is carried far enough posteriorly to damage portions of the anterior hippocampus and hippocampal gyrus. This conclusion is based on formal psychological testing of nine cases (eight psychotic and one epileptic) carried out from one and one-half to four years after operation. The degree of memory loss appears to depend on the extent of hippocampal removal. In two cases in which bilateral resection was carried to a distance of 8 cm posterior to the temporal tips the loss was particularly severe. Removal of only the uncus and amygdala bilaterally does not appear to cause memory impairment. A case of unilateral inferior temporal lobectomy with radical posterior extension to include the major portion of the hippocampus and hippocampal gyrus showed no lasting memory loss. This is consistent with Milner and Penfield's negative findings in a long series of unilateral removals for temporal lobe epilepsy. The memory loss in these cases of medial temporal lobe excision involved both anterograde and some retrograde amnesia, but left early memories and technical skills intact. There was no deterioration in personality or general intelligence, and no complex perceptual disturbance such as is seen after a more complete bilateral temporal lobectomy. It is concluded that the anterior hippocampus and hippocampal gyrus, either separately or together, are critically concerned in the retention of current experience. It is not known whether the amygdala plays any part in this mechanismi, since the hippocampal complex has not been removed alone, but always together with uncus and amygdala.     

Ictal fear in temporal lobe epilepsy: surgical outcome and focal hippocampal changes revealed by proton magnetic resonance spectroscopy imaging

BACKGROUND: Ictal fear (IF) is most frequently associated with epileptic discharges from mesial temporal areas. OBJECTIVES: To determine whether patients with IF were more likely to become seizure free after anteromesial temporal lobe resection compared with those without IF and whether they show more anteriorly pronounced metabolic changes assessed by means of multivoxel magnetic resonance spectroscopy (MRS) along the hippocampal axis. METHODS: Surgical outcome was assessed in 33 consecutive patients with temporal lobe epilepsy after a mean follow-up of 25 months (range, 12-38 months). Proton multivoxel MRS of the hippocampal formation was applied to detect regional differences along the axis of the hippocampus in patients with and without IF. Magnetic resonance tomography showed typical features of hippocampal sclerosis in all patients. RESULTS: Twelve (36%) of the 33 patients reported fear at the beginning of their habitual seizures. Eleven of these patients were seizure free postoperatively. In contrast, only 11 of 21 patients without IF had a favorable outcome. Results of MRS revealed significantly higher pathologic N-acetylaspartate-choline ratios in the anterior portion of the hippocampal formation in patients with than in those without IF, indicating focal metabolic and/or morphologic changes in the head of the hippocampus. CONCLUSIONS: These results indicate the importance of diagnosing auras with IF to provide a more detailed prognosis of the surgical outcome. In addition, our data emphasize that multivoxel MRS is a valuable tool in the presurgical evaluation, as it may reveal different topographical patterns of hippocampal sclerosis.     

Volumetric evidence of a left laterality effect in epileptic psychosis

We investigated anatomic alterations and lateralization effect in the mesial temporal lobe structures (amygdala and hippocampus) in epileptic psychosis MRI volumetric measurements. Patients with epileptic psychosis and normal controls were studied. Left hippocampus values were significantly smaller for patients (P<0.001). Hippocampal ratio was significantly greater for patients (P<0.01). Group (patients x normal) was the only factor explaining the statistically significant variation of left hippocampus and hippocampal ratio (P<0.001 and P<0.05). Twenty patients had hippocampal atrophy (4 on the right side, 15 on the left side, and 1 bilateral) associated with mesial temporal sclerosis. These results confirm the existence of anatomic alterations and a left laterality effect in the mesial temporal lobe structures of patients with epileptic psychosis.     

Resective surgery is possible in patients with temporal lobe epilepsy due to bilateral isolated hippocampal malformation

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.     

Hippocampal volume and glucose metabolism in temporal lobe epileptic foci

PURPOSE: Reports conflict on the relation of glucose metabolism to hippocampal volume in temporal lobe foci. Previous studies usually have used side-side ratios rather than regional metabolic rates. METHODS: We measured hippocampal volume and glucose metabolism in 37 patients with temporal epileptogenic zones identified by ictal video-EEG telemetry. Metabolic rates were normalized to global brain mean. RESULTS: Both 18-fluoro-2-deoxyglucose-PET and volumetric MRI lateralized the epileptic focus determined by ictal video-EEG. There were significant correlations between left-right metabolic asymmetry and hippocampal formation volume left-right ratios. Comparisons between normalized metabolism and hippocampal formation volume, ignoring the side of the epileptic focus, showed significant relations between left hippocampal volume and left inferior lateral temporal metabolism, right hippocampus and right inferior mesial temporal, and left hippocampus and left inferior mesial temporal metabolism. In contrast, when normalized metabolism was compared with hippocampal volume in the epileptic focus, no relation was found. CONCLUSIONS: Our study suggests that the relation between hippocampal volume and glucose metabolism breaks down in epileptic foci and that hypometabolism is not dependent on neuronal loss. It is consistent with data suggesting that hypometabolism is an independent predictor of surgical outcome.     

Experimental Models of Temporal Lobe Epilepsy: New Insights from the Study of Kindling and Synaptic Reorganization

Summary: Temporal lobe epilepsy is a common localization-related epileptic syndrome characterized by complex partial seizures, ictal and interictal epileptic discharges arising from limbic structures of the temporal lobe, and association with hippocampal sclerosis. Temporal lobe epilepsy may follow perinatal injury and febrile convulsions, may be progressive, and frequently becomes refractory to standard antiepileptic therapy. The neurobiology that underlies these features of temporal lobe epilepsy is not known. Recent studies in experimental models have provided new insights that may help clarify the relationship of seizures, hippocampal sclerosis, and temporal lobe epilepsy. Observations from the study of the hippocampus with kainic acid-induced lesions, the kindling model, and other experimental models of epilepsy have demonstrated that seizures induce structural and electrophysiologic alterations in hippocampal pathways that may lead to increased excitability and could play a role in the development and progression of temporal lobe epilepsy. These alterations include mossy fiber synaptic reorganization, induction of NMDA-mediated synaptic transmission, and progressive hippocampal neuronal loss induced by brief kindled seizures. Some of the structural alterations induced by kindling have also been observed in the human epileptic temporal lobe, raising the possibility that mechanisms operative in kindling may play a role in the pathogenesis of hippocampal sclerosis and in the syndrome of human temporal lobe epilepsy.     

Long-term neuropsychological follow-up of a child with Klüver-Bucy syndrome

We describe the case of a 10-year-old girl who developed behavioral changes consistent with Klüver-Bucy Syndrome following Listeria meningoencephalitis at 2? years of age. MRI at age 4 revealed evidence of diffuse brain atrophy with predominant temporal lobe involvement. Electroencephalograpy at 9? years of age showed abnormal electrical discharges from the left temporal area. Follow-up MRI with volumetric analysis of the mesial temporal structures at 9 years of age demonstrated decreased hippocampal volume bilaterally. Consistent with the morphological abnormalities, serial neuropsychological evaluations demonstrated expressive and receptive language impairment and an amnestic syndrome that significantly decreased her ability to make new declarative memories and maintain adequate academic progress.     

Additional hippocampectomy in the surgical management of intractable temporal lobe epilepsy associated with glioneuronal tumor

In surgery for epileptogenic glioneuronal tumor in the temporal lobe, whether additional hippocampectomy is needed remains in dispute. We retrospectively analysed clinical profile and seizure outcome in a consecutive series of six patients, paying special attention to pathophysiologic conditions in the ipsilateral hippocampus. Long-term video electroencephalography (EEG) monitoring showed attenuation of background activity, followed by ictal discharges in the ipsilateral temporal region in five cases. (18)Fluorodeoxyglucose-positron emission tomography (FDG-PET) in five cases showed hypometabolism in the ipsilateral medial temporal lobe. Intraoperative electrocorticography (ECoG) after removal of the tumor revealed frequent paroxysmal activity or electrographic seizure activity on the hippocampus in five cases. A high incidence of hippocampal pathology, such as hippocampal sclerosis in four cases and dysgenesis in one case, was demonstrated. Five patients who underwent additional hippocampectomy along with resection of the tumor became completely seizure-free. Our findings indicated a proclivity for the epileptogenic zone to encompass the medial structures and for hippocampal pathology to be present even when no direct medial tumor involvement was identified. Thus, it is conceivable that removal of the hippocampus with the guidance of pre- and intraoperative multimodal examinations, in addition to resection of the tumor, may be recommended to achieve 'complete' freedom from seizures.     

A case with left mesial temporal lobe epilepsy characterized by abnormal massive salivation]

A 26-year-old woman was admitted because of a 12-year history of intractable epileptic seizures. Every seizure began with an upper abdominal discomfort, and often followed by massive salivation. Whenever the epileptic salivation happened, the patient lost consciousness, and sometimes she developed generalized convulsions. In terictal sphenoidal EEG recordings revealed abnormal discharges in the left mesial temporal region. MRI demonstrated left hippocampal atrophy. Since her seizures were medically intractable, left temporal lobectomy was performed. Neuropathologic examination revealed hippocampal sclerosis. After the operation, she became completely seizure-free with no episode of massive salivation. From the literature, epileptic salivation can originates from the rolandic area; fronto-orbital cortex & cingulate gyrus; insula & operculum; and mesial temporal structures. The abnormal massive salivation in our patient might be attributable to the activation of frontal limbic system triggered by hippocampal abnormal firing during the ictal period of TLE.     

Postoperative recovery of hippocampal contralateral diffusivity in medial temporal lobe epilepsy

PURPOSE: To search for a recovery after surgery of mean diffusivity (MD) values in the contralateral nonsclerotic hippocampus of patients with medial temporal lobe epilepsy (MTLE) and hippocampal sclerosis (HS). METHODS: Twenty-four MTLE patients (12 right-sided and 12 left-sided MTLE) and 36 healthy volunteers were investigated using diffusion tensor imaging. A region-of-interest approach was used to measure pre- and postoperative interictal hippocampal MD values in patients. RESULTS: Diffusion abnormalities in contralateral nonsclerotic hippocampus recovered after surgery (p<0.0001). A subgroup of 14 patients exhibited a clear increase in MD values whereas the remaining 10 patients were stable. No significant difference was found between the two subgroups for each of the electroclinical data studied including early postoperative outcome, all patients being either seizure free or with rare persistent auras. CONCLUSIONS: This finding suggests that diffusion abnormalities in contralateral hippocampus may represent a functional mechanism linked to the active epileptic process.     

Dual pathology in a patient with temporal lobe epilepsy associated with neocortical glial scar after brain abscess and end folium sclerosis/hippocampal sclerosis type 3

End folium sclerosis or hippocampal sclerosis (HS) type 3 is often associated with another coexisting epileptogenic lesion (dual pathology); however, the pathogenesis of HS type 3 remains elusive. A 46‐year‐old man presented with medically intractable focal aware seizures and focal impaired awareness seizures (FIAS) with occasional focal to bilateral tonic–clonic seizures (FBTCS) two years after surgical treatment with extensive cranial reconstruction for a brain abscess in the right temporal lobe associated with intracranial extension of ipsilateral cholesteatoma. Head magnetic resonance imaging (MRI) at age 49 revealed atrophy of the right cerebral hemisphere including the hippocampus and amygdala. The patient's first epilepsy surgery was a lateral temporal lobectomy, in which the mesial temporal structures were preserved because no epileptiform discharge was detected on the intraoperative electrocorticogram. However, FIAS with FBTCS started 15 months after the operation. The second surgery, amygdalohippocampectomy, at age 52, resulted in the patient being seizure‐free again for one year before seizures of the right lateral temporal origin recurred. He underwent a third surgery, resection of the Heschl's and supramarginal gyri, at age 53, but he continued to have drug‐resistant epilepsy over two years after that. Histopathological examination revealed dual pathology consisting of glial scar in the lateral temporal lobe and ipsilateral HS type 3 with an unusually severe lesion in the subiculum. No significant inflammatory change was observed. The clinicopathological features in the present case indicate that HS developed secondarily in the context of neocortical epilepsy due to glial scar, suggesting a role of repetitive abnormal electrical input from neocortical epileptogenic lesions into the hippocampus finally via the perforant pathway in the pathogenesis of HS type 3. Severe hippocampal atrophy on preoperative MRI together with its silent electrocorticogram recording at initial epilepsy surgery may represent clinically pre‐epileptogenic HS in a seizure‐free “silent or latent period” before completion of hippocampal epileptogenesis to the extent that clinical epileptic seizures occur.     

Acute hippocampal recording and pathology at temporal lobe resection and amygdalo-hippocampectomy for epilepsy.

An electrocorticographic (ECoG) study is reported of patients undergoing surgery for epilepsy of temporal lobe origin. During 22 en bloc resections and six out of a total of 18 amygdalo-hippocampectomies, the activity of the hippocampus was also recorded by a multipolar strip electrode placed along its axis on the ventricular surface. Patients with mesial temporal pathology, chiefly mesial temporal sclerosis, made up the majority of those selected for amygdalo-hippocampectomy. They showed a characteristic ECoG pattern, with spikes localised to the mid part of the second and third convolutions and inferior aspect of the temporal lobe. Typically, this was associated with hippocampal discharges showing an anterior maximum. Pathology involving lateral temporal neocortex and non-specific findings were associated with more widespread temporal spikes and a maximum discharge amplitude over the mid and posterior parts of the hippocampus. It is suggested that intraoperative recording of the ECoG and hippocampal activity may provide a guide to the choice between en bloc resection and amygdalo-hippocampectomy.     

The chicken with four legs: a case of semantic amnesia and cryptogenic epilepsy

Here we describe the unusual condition of selective semantic amnesia related to cryptogenic temporal lobe epilepsy. XY, an adult male patient, presented with partial seizures and disabling dysnomia. Neuropsychological tests revealed seriously impaired semantic memory. Electroencephalography documented ictal epileptic abnormalities in the left temporal lobe. Positron emission tomography showed reduced metabolism in the temporoparietal regions, but the results of magnetic resonance imaging and spectroscopy were normal. After 11 years, neuropsychological tests showed selective impairment of semantic memory and computed tomography provided normal results. This case shows that semantic memory may be selectively and lastingly altered, highlighting a distinction between semantic amnesia and global amnesia. Moreover, it is unique in that it occurred without evidence of gross temporal lobe pathology. The pathophysiological pattern of epileptic abnormalities in the left temporoparietal cortex supports the role played by dysfunctional neuronal networks (as provoked by focal epileptic discharges) in determining selective semantic amnesia.     

A Correlative Study between Hippocampal Atrophy Quantified by Tomo-Pneumoencephalography and Epileptogenic Focus in Temporal Lobe Epilepsy

It appeared certain that we can quantify the rate of hippocampal atrophy by utilizing the sagittal cuts in tomo-pneumoencephalog-raphy. This is a reliable method to infer the side of the epileptogenic focus in temporal lobe epilepsy since a close correlation was disclosed between the side with more atrophic features of the hippocampus and that of the epileptogenic focus explored by depth EEG, in particular, in the mesial temporal focus group. On the other hand, it seems to be plausible that the hippocampal atrophy could be secondarily induced by epileptic discharges in the lateral temporal group. Namely, controversies dealing with the casual relationship of hippocampal atrophy should be discussed based on the epileptogenic focus localization in temporal lobe epilepsy.     

Verbal memory impairment correlates with hippocampal pyramidal cell density

Thirty-five patients with medically refractory epilepsy localized to the temporal lobe (18 left, 17 right) completed the verbal Selective Reminding Test before surgery. Verbal memory impairments existed before surgery regardless of the lateralization of the seizure focus, but patients with left temporal seizure foci were significantly more impaired. After surgical removal of the mesial temporal lobe structures, 2 blinded observers established volumetric cell densities for hippocampal subfields CA1, CA2, CA3, the hilar area, and the granule cell layer of the area dentata. Statistically significant correlations existed between presurgical memory impairment and cell counts (in CA3 and the hilar area, only) for patients with left temporal seizure foci. These findings support the hippocampal model of memory and complement prior research documenting the memory impairments present after surgical removal of the mesial temporal structures.     

A controlled quantitative MRI volumetric investigation of hippocampal contributions to immediate and delayed memory performance

MRI volumetric TLE studies show inconsistent evidence of hippocampal involvement in memory. Prior studies have not dissociated hippocampal and temporal lobe contributions to memory. We measured hippocampal and temporal lobe volumes and immediate/delayed memory performances in 64 TLE patients. Regression was used to dissociate hippocampal from temporal lobe contributions to memory. Results revealed reliable evidence for dominant hippocampal involvement in delayed verbal recall across three separate measures and less consistent evidence for nondominant hippocampal involvement. The findings point to a consistent relationship of dominant hippocampal volumes to delayed verbal recall but no involvement of the temporal lobe or nondominant hippocampus in memory.     

Accelerated long-term forgetting in temporal lobe epilepsy: evidence of improvement after left temporal pole lobectomy

Accelerated long term forgetting (ALF) is a characteristic cognitive aspect in patients affected by temporal lobe epilepsy that is probably due to an impairment of memory consolidation and retrieval caused by epileptic activity in hippocampal and parahippocampal regions. We describe a case of a patient with TLE who showed improvement in ALF and in remote memory impairment after an anterior left temporal pole lobectomy including the uncus and amygdala. Our findings confirm that impairment of hippocampal functioning leads to pathological ALF, whereas restoration of hippocampal functioning brings ALF to a level comparable to that of controls.