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Biomedical subjects

A Olivier

Publications and source records attributed to A Olivier.

At least 19 recordsLinked to original sources

Obligatory role of the LIFG in synonym generation: evidence from PET and cortical stimulation.

We report results from a patient in whom we obtained converging evidence from positron emission tomography (PET) and intraoperative stimulation mapping to support a one-way dissociation between the functional areas involved in word repetition and synonym generation. Intraoperative stimulation mapping interfered with synonym generation but did not disturb word repetition at the same left inferior frontal site at which a cerebral blood flow (CBF) increase had been observed for a synonym generation task. The results for this single subject suggest that the functional areas involved in different aspects of linguistic processing are dissociable and that specific disruption under conditions of cortical stimulation can be correlated with the brain regions identified via PET as the most active during performance of a specific task.

Adult

The promoting effects of bFGF and astrocyte extracellular matrix on process outgrowth by adult human oligodendrocytes are mediated by protein kinase C.

Process extension by oligodendrocytes (OLs) is a critical early step in myelin formation. We have previously reported that the basal- or phorbol ester-enhanced process outgrowth by adult human OLs is mediated by oligodendroglial protein kinase C (PKC). Recently, we demonstrated that astrocytes facilitated process outgrowth by adult human OLs through the interaction between astrocyte-derived basic fibroblast growth factor (bFGF) and astrocyte extracellular matrix (ECM). If PKC is central to the signal transduction cascade that leads to process formation by OLs, then the effects of bFGF and astrocyte ECM should also involve PKC. In the current study, we have addressed the involvement of PKC in the bFGF- and astrocyte ECM- enhanced process formation by adult human OLs by using a selective inhibitor of PKC, calphostin C. The results show that calphostin C dose-dependently reduced process extension elicited by bFGF and astrocyte ECM, at IC50 concentrations of 24.5 and 26.6 nM, respectively. At the concentrations of calphostin C that inhibited process extension by adult human OLs, necrosis (measured by lactate dehydrogenase release) and apoptosis (determined by using a fluorescent terminal deoxynucleotidyl transferase assay) of OLs did not occur. Finally, we demonstrate that another specific inhibitor of PKC, CGP 41251, also reduced process formation that is elicited by bFGF and astrocyte ECM. Thus, all process-extending agents for adult human OLs identified to date signal through PKC, further implicating PKC of OLs as being central to the production of process extension, an early event in myelinogenesis.

Astrocytes

Periventricular nodular heterotopia and intractable temporal lobe epilepsy: poor outcome after temporal lobe resection.

We describe 5 women and 5 men with periventricular nodular heterotopia and electroclinical features suggestive of temporal lobe epilepsy, who were surgically treated for control of medically refractory seizures. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia in 7 of the 10 patients. Because of the lack of clear localization, 6 patients were studied with intracranial depth electrode recordings. Seizures were of hippocampal onset (3 patients), regional temporal lobe onset (2 patients), or occipital-temporal onset (1 patient). Anterior temporal lobectomy was performed in 6 patients; selective amygdalohippocampectomy, in 1; and anterior temporal lobectomy plus resection of the heterotopic tissue, in 3. None of the 9 patients followed for more than 12 months postoperatively were seizure free. Two patients were initially seizure free for approximately 18 months, but then seizures recurred. One patient had a major reduction in seizure frequency at a 39-month follow-up after most of the unilateral heterotopic tissue was included in the temporal resection. Temporal resection did not lead to a long-term favorable outcome in this group of patients with periventricular nodular heterotopia and epileptogenic discharges involving the temporal lobe. This suggests a more widespread disorder with epileptogenic activity possibly originating in or near the heterotopic tissue. The clinical and electrographic features of periventricular nodular heterotopia pointing to temporal lobe origin are misleading and temporal resection does not result in long-term cessation of seizures.

Adult

Mesial temporal versus lateral temporal interictal epileptiform activity: comparison of chronic and acute intracranial recordings.

Intracranial interictal epileptiform activity (EA) was recorded by chronic stereotactic depth electroencephalography (SDEEG) and acute electrocorticography (ECOG) in 22 patients with complex partial seizures of temporal lobe origin. Chronic SDEEG recordings defined two groups of patients with respect to the presence or absence of lateral temporal EA; 13 patients showed independent lateral temporal EA during chronic recordings and 9 patients did not. All patients had EA recorded from mesial temporal structures during SDEEG. The presence of lateral temporal EA was correlated with a higher pre-operative seizure frequency but not with ictal onset zones, structural pathology, age at onset of epilepsy, or duration of epilepsy. Results of acute ECOG recordings performed on the same patients 1-24 months after SDEEG accurately reproduced the mesial versus lateral distribution of EA within patients (P < 0.0003). Though ECOG was less sensitive than SDEEG in demonstrating EA confined to mesial structures, positive findings at ECOG were 100% specific with respect to SDEEG. These results suggest that, at least with respect to mesial temporal versus lateral temporal structures, there is a constancy within patients in the distribution of interictal EA recorded with chronic intracranial electrodes. In addition, acute ECOG provides an accurate representation of individual patients' interictal EA.

Adult

Learning and retention of words and designs following excision from medial or lateral temporal-lobe structures.

We sought to elucidate the contributions of the amygdala, hippocampus and temporal neocortex to learning and memory for verbal and visuospatial material. Two matched learning tasks, using abstract words versus abstract designs, were administered to patients with unilateral neocorticectomy (NCE; Dublin), selective amygdalohippocampectomy (AHE; Zurich) or anterior temporal-lobe resection invading the amygdala and hippocampus (ATL; Montreal). Data were analysed according to side and type of resection. Learning and recall for words was impaired in groups with resection from the left temporal lobe, irrespective of whether mediobasal structures were spared or temporal neocortex was spared. All right-resection groups were unimpaired. Learning for abstract designs was impaired across all trials in the right AHE and NCE groups, and on the last two trials in the right ATL group. Restricted deficits of lower magnitude were observed on some trials in left-resection groups. These results show a partial dissociation between side of excision and type of material, but the finding of similar deficits in all resection types was unexpected. We propose that excision from either the hippocampal region or temporal neocortex may result in a disconnection, giving a similar functional outcome, as both types of resection interrupt a circuit likely to be essential for normal storage and retrieval of information.

Amygdala

Induction of burst-suppression and activation of epileptiform activity after methohexital and selective amygdalo-hippocampectomy.

Electrocorticography (ECOG) compared the effects of methohexital (MTH) and selective amygdalo-hippocampectomy (selAH) upon lateral temporal neocortical epileptiform activity (EA) in 31 patients with mesial temporal epilepsy. Pre-excision ECOG showed independent neocortical EA before MTH in 12/31 and after MTH in 18/31. MTH (20-50 mg) activated neocortical EA in 12 cases and induced burst-suppression (BS) over temporal neocortex in 14/31. Post-excision ECOG showed neocortical EA in 21/31 and BS in 27/31: compared with pre-excision ECOG before MTH, selAH activated neocortical EA in 15 cases. Significant correlations were found between presence of pre-excisional neocortical EA and presence of post-excisional neocortical EA (P < 0.001) and between activation of pre-excisional neocortical EA by MTH and activation of (post-excisional) neocortical EA by selAH (P < 0.006). Presence or severity of BS in the post-excision ECOG was not correlated with presence, absence or activation of post-excisional EA. Presence of neocortical EA was significantly correlated with a higher pre-operative seizure frequency (P < 0.001) but not with duration of epilepsy nor surgical outcome. Both MTH and selAH can induce neocortical BS, likely through chemical and surgical disconnection of cortex, respectively. Unrelated to induction of BS, MTH and selAH appear to decrease threshold for expression of neocortical EA in a similar fashion.

Adolescent

Contribution of medial versus lateral temporal-lobe structures to human odour identification.

To investigate possible distinct contributions of different temporal-lobe structures to odour identification, the University of Pennsylvania Smell Identification Test was administered monorhinally to seizure-free patients who had undergone one of three types of temporal-lobe resection practised in three different institutions for surgical treatment of epilepsy. The resections were neocorticectomy (Dublin), selective amygdalohippocampectomy (Zurich), or anterior temporal-lobe resection with encroachment on amygdala and hippocampus (Montreal). Resections, analysed from MRI scans, showed unexpected encroachment on medial structures in most patients of the neocorticectomy groups, and largest amygdala and hippocampal resections in the amygdalohippocampectomy groups. Impaired odour identification was observed in all patient groups, irrespective of surgical approach, with greatest impairment in the nostril ipsilateral to the resection. The finding of deficits in all three surgical groups suggests that damage in the anterior temporal area, perhaps in piriform cortex, is sufficient to disrupt performance on this task; it may be that function is disrupted in the medial temporal-lobe region by disconnection when the periamygdaloid area is damaged, even when amygdala and hippocampus are left intact. An alternative explanation for our results is that damage in any one of these areas disrupts a complex network involving several distinct temporal-lobe structures.

Adolescent

The fibroblast population in oral submucous fibrosis.

The purpose of the investigation was to compare the morphology of fibroblasts cultured from healthy oral mucosa and mucosa of patients with oral submucous fibrosis (OSF) and to collate the occurrence of cell types of similar morphology. Cells cultured from biopsy specimens from the buccal mucosa of six subjects who did not chew the areca nut and six patients with OSF who chewed areca nut were grown according to standard techniques. Ninety cells per cell line were recorded daily for 8 days, classified into types F1, F2 and F3 according to their morphology, and the results statistically analyzed. We found that there was a relative increase of F3 cells in relation to F1 cells in OSF, resulting in the ratio of F3 to F1 cells being significantly larger in OSF than the ratio in the controls. As it has been reported that F3 cells in rat connective tissues produce significantly more collagen types I and III than F1 cells, we concluded that a change of fibroblast population has occurred in OSF and that this relative increase of F3 cells in humans, which could be committed to the production of large quantities of collagen, can be an explanation for the excessive collagen formation in OSF.

Adult

Surgical treatment of patients with single and dual pathology: relevance of lesion and of hippocampal atrophy to seizure outcome.

Modern neuroimaging can disclose epileptogenic lesions in many patients with partial epilepsy and, at times, display the coexistence of hippocampal atrophy in addition to an extrahippocampal lesion (dual pathology). We studied the postoperative seizure outcome of 64 patients with lesional epilepsy (median follow-up, 30 months) and considered separately the surgical results in the 51 patients with a single lesion and in the 13 who had dual pathology. In patients with a single lesion, 85% were seizure free or significantly improved (Engel's class I-II) when the lesion was totally removed compared with only 40% when there was incomplete resection (p < 0.007). All three patients with dual pathology who had both the lesion and the atrophic hippocampus removed became seizure free. In contrast, only 2 of the 10 patients with dual pathology undergoing surgery aimed at the lesion or at the hippocampus alone became seizure free (p < 0.05), although 4 of them showed significant improvement (Engel's class II). We conclude that the outcome in patients with single epileptogenic lesions is usually dependent upon the completeness of lesion resection. In patients with dual pathology, surgery should, if possible, include resection of both the lesion and the atrophic hippocampus.

Adolescent

Mesial atrophy and outcome after amygdalohippocampectomy or temporal lobe removal.

We studied 74 consecutive patients with temporal lobe epilepsy who were treated surgically and in whom the volumes of mesial temporal structures were determined preoperatively by magnetic resonance imaging. We divided the patients into three groups according to the volumetric findings: unilateral (63.5% of the patients), bilateral (23%), or no atrophy (13.5%) of the amygdala-hippocampal formation. Two distinct surgical approaches were used: selective amygdalohippocampectomy (n = 37) or anterior temporal lobe resection (n = 37). Outcome was assessed at least 1 year after surgery, according to Engel's modified classification. Patients with unilateral mesial temporal atrophy had significantly better results compared with the other two groups (p < 0.001): We found excellent results (class I or II outcome) in 93.6% of the patients with unilateral atrophy, in 61.7% of those with bilateral atrophy, and in 50% of the group with no significant atrophy of mesial temporal structures. The two different surgical techniques were equally effective, regardless of the pattern of atrophy. In conclusion, magnetic resonance volumetric studies in temporal lobe epilepsy proved to be an important preoperative prognostic tool for surgical treatment, but they did not provide guidance for selecting one surgical approach compared to the other.

Adult

Low-grade pure and mixed cerebral astrocytomas treated in the CT scan era.

From 1974 to 1992, 63 patients diagnosed with low-grade pure or mixed oligo-astrocytoma were seen and treated at our institution. All patients underwent CT scan pre-operatively. There were 20 female and 43 males ranging in age from 12 to 73 years (median age of 33 years). 15 patients had a stereotactic biopsy as the only surgical procedure. 34 had a partial tumor resection and 14 a gross total tumor resection. 43 patients were treated with post-operative radiotherapy whereas 20 patients underwent surgery only as part of the initial management. 50 to 60 Gy (median 59.4 Gy) were given with daily fractions of 1.8 to 2 GY. Tumor volume ranged from 3.4 to 441 cm3. Median tumor volume was larger for radiotherapy treated patients. Median follow-up was 54 months (range of 4 to 240 months). The overall 10 and 15 actuarial survival rates were 37% and 25% respectively. The 5 years survival rate for patients treated at initial diagnosis with surgery alone was 66% and it was 67.3% for patients treated with radiation therapy (P = NS). Prognostic factors having independent significant impact on survival were: extent of surgery, age gender and tumor volume. As well, survival for patients with low-grade astrocytoma in the CT scan era appears to be improved compared to historical controls in the literature.

Adolescent

Usefulness of focal rhythmic discharges on scalp EEG of patients with focal cortical dysplasia and intractable epilepsy.

We examined the significance and frequency of occurrence of rhythmic epileptiform discharges (REDs) on the scalp EEGs of 74 patients with intractable partial epilepsy. We also analyzed the relationship of this abnormality to the continuous epileptiform discharges (CEDs) recorded on ECoG. Both REDs and CEDs had been found to be highly specific and sensitive indicators of focal cortical dysplastic lesions. Thirty-four patients (group I) had focal cortical dysplastic lesions (FCDLs) and 40 (group II) had non-dysplastic structural lesions. REDs were observed in 15 (44%) of the 34 patients of group I and in none of group II. REDs did not occur in isolation, were associated with more intermittent interictal spikes involving other regions, but had a greater (P < 0.05) significance for the localization of the epileptogenic area. A strong relationship was observed between the presence of REDs on scalp EEG and the occurrence of CEDs on ECoG recordings. Twelve (80%) of 15 patients with REDs had CEDs. Focal cortical dysplastic lesions are likely to be present when rhythmic epileptiform discharges are found.

Adolescent

Relationship between structural properties and affinity for herpes simplex virus type 1 thymidine kinase of bromine substituted 5-heteroaromatic 2'-deoxyuridines.

The crystal structures of 5-(5-furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (IV) and 5-(3-bromothien-2-yl)-2'-deoxyuridine (V) have been studied in order to explain the different affinity of the compounds for the herpes simplex virus type 1 (HSV-1) thymidine kinase. These compounds present a variable affinity according to the position of the heteroatom substituting the five-membered ring. An unfavourable substitution in the five-membered ring for interaction with the HSV-1 thymidine kinase has been identified.

Antiviral Agents

Surgical treatment of epilepsy: the problem of lesion/focus incongruence.

BACKGROUND: This study suggests an alternative surgical strategy for treating patients with intractable epilepsy in whom a lesion, visualized by imaging, is found to be at a distance from the maximal electroencephalographic abnormality (focus). METHODS: Sixty patients (divided into three groups of 20), all of whom have had surgical resection for intractable epilepsy, are reviewed. Group A patients, representing the most common situation of a congruent electroencephalographic focus and structural lesion, underwent resection of the lesion/focus. Group B patients, in whom the focus and the lesion are incongruent, underwent resection of the focus only. Group C patients are those where the focus and lesion are incongruent; in this group, the lesion only was resected. RESULTS: Group A patients underwent resection of the lesion/focus (sites: 13 temporal, six frontal, and one parietal) with excellent results. Group B patients, in whom the focus only was resected (lesion sites: 14 temporal, four parietal, and two occipital) obtained poor results. Group C patients had excellent results following resection of the lesion only (lesion sites: 12 temporal, seven frontal, and one parietal). The superior surgical outcome in seizure control of group C is comparable to that seen in group A (Chi2 contingency test; Chi2 = 3.27 p > .05, 3 degrees of freedom) and is in contrast to the poor results seen in group B (Chi2 = 20.59 p < .001, 3 degrees of freedom). CONCLUSION: In those patients where a choice between a focus and a lesion is imperative, the lesion detected by imaging should be given priority in surgical resection.

Brain Diseases

Neuronal migration disorders and epilepsy: a morphological analysis of three surgically treated patients.

Despite the increasing number of patients affected by neuronal migration disorders (NMDs) recently diagnosed in vivo by means of magnetic resonance imaging (MRI), few detailed data on the correlation between the neuroradiological and the anatomical features in the single NMD case are available. The present paper reports a combined cytoarchitectural and immunocytochemical analysis, by means of antisera recognizing specific neuronal and glial markers, of three MRI diagnosed NMD patients surgically treated for the relief of intractable seizures. The first case was a giant subcortical nodular heterotopia of morphologically normal neurons lacking any type of cortical lamination. The second case was a layered polymicrogyria with an abnormal amount of ectopic neurons in the underlying white matter. The third case was a focal cortical dysplasia characterized by a dramatic disruption of the normal cortical layering associated with marked cytological abnormalities. The present data demonstrate that the macroscopical and microscopical brain abnormalities can be markedly different in different NMD subtypes, and suggest that different anatomical substrates can underlie the intrinsic hyperexcitability of these brain malformations. The relevance of further prospective clinico-morphological studies for a better understanding of the mechanisms determining the development of these brain malformations is underlined.

Brain

Post-traumatic frontal lobe epilepsy with structural changes: excellent results after cortical resection.

BACKGROUND: The observation that resection of structural lesions of the frontal lobe provides an effective treatment of intractable epilepsy has been made by surgeons specializing in this field for over sixty years! However, the excellent results achieved when such resections are coupled with the use of modern diagnostic and operative technologies are not fully appreciated by the modern clinician. METHODS: We review the results of resection of large post traumatic frontal lesions in six patients with intractable frontal seizures. No invasive EEG recording was required pre-operatively. RESULTS: The imaging characteristics of the underlying lesions, usually due to depressed skull fractures are illustrated. Surgical treatment rendered five patients seizure free and the sixth had over 85% improvement in seizure frequency. CONCLUSIONS: Modern imaging permits ready visualization of the post traumatic lesions with cause intractable seizures. It is important to recognize that resection of these post traumatic scars usually leads to excellent seizure control.

Adolescent

Accurate, noninvasive diagnosis of human brain tumors by using proton magnetic resonance spectroscopy.

Although conventional proton magnetic resonance imaging has increased our ability to detect brain tumors, it has not enhanced to nearly the same degree our ability to diagnose tumor type. Proton magnetic resonance spectroscopy is a safe, noninvasive means of performing biochemical analysis in vivo. Using this technique, we characterized and classified tissue from normal brains, as well as tissue from the five most common types of adult supratentorial brain tumors. These six tissue types differed in their pattern across the six metabolites measured. 'Leaving-one-out' linear discriminant analyses based on these resonance profiles correctly classified 104 of 105 spectra, and, whereas conventional preoperative clinical diagnosis misclassified 20 of 91 tumors, the linear discriminant analysis approach missed only 1. Thus, we have found that a pattern-recognition analysis of the biochemical information obtained from proton magnetic resonance spectroscopy can enable accurate, noninvasive diagnosis of the most prevalent types of supratentorial brain tumors.

Adult

The running down phenomenon in temporal lobe epilepsy.

We compared 100 patients with temporal lobe epilepsy, who exhibited the running down phenomenon following temporal resections, with two groups of patients: 100 patients who became seizure-free, and 100 patients who continued to have frequent seizures following temporal resection. We found a significant correlation between prognosis and the size of the epileptogenic area as defined; patients with smaller epileptogenic areas had the best prognosis (seizure-free group). Patients exhibiting the running down phenomenon had intermediate size epileptogenic areas, while those patients who continued to have seizures had the largest epileptogenic areas often involving the lateral temporal and posterior temporal cortex. Other factors predictive of good outcome were: a history of febrile seizures, predominantly unilateral interictal spiking, anterior temporal localization, extent of resection of the mesial temporal structures, surgery under the age of 30 years, and the absence of habitual seizures in the immediate postoperative period. Patients with history of head trauma, encephalitis, posterior temporal localization and bitemporal spiking had a worse outcome. The frequency and types of aurae, and laterality of resection did not correlate with outcome.

Adolescent