[Old and new tobacco products]. / Les anciens et nouveaux produits du tabac.

Tobacco use is not just about manufactured cigarettes. Rolling tobacco, highly prized in the wake of price increases, is estimated to carry more toxic agents than its counterpart. This study shows that the use of cigar, pipe, cigarillos and narghile also leads to a cohort of pathologies similar to or more than what is known for smoking single cigarettes. Exotic, liquid or heated forms do just as much. The non-smoked tobacco, often fallen into disuse in France is very used in the United States and especially in Scandinavia. Denuded of inhaled products, it is often pointed as a form of reduction of smoking risks. Its use by athletes in all countries as a doping attitude, especially in ski disciplines, required a campaign of prevention within the federations concerned.

Practical guidelines on e-cigarettes for practitioners and others health professionals. A French 2016 expert's statement.

A group of 11 French medical experts has developed guidelines through a Delphi progressive consensus about smoking management at the e-cigarette era. The lack of scientific data about e-cigarettes led the experts to set out recommendations, mainly based on clinical practice while waiting for scientific validations. The validated smoking cessation treatments keep the first place in the prevention and the treatment of tobacco-induced damages. The e-cigarette, experimented by a large proportion of smokers, is a safer product than tobacco. The health professional must answer the patients about the e-cigarettes: (1) A smoker who questions about e-cigarettes should receive information. Even if there is a lack of data, e-cigarettes offer much lower risks than tobacco. (2) A dual user is at high risk of returning to exclusive tobacco use; he should also optimize other nicotine intakes by combining nicotine replacement therapy and/or optimizing the nicotine intake through the e-cigarette. (3) A smoker who wish to use the e-cigarette in order to quit with or without associated pharmacological treatment should be accompanied and not discouraged. (4) A vaper who is tired to continuing to vape should be accompanied to quit. Specific guidelines are also provided for adolescents, pregnant women, patients during perioperative periods and also for pulmonary, cardiac and schizophrenic patients.

[Depression in smoking pregnant women: impact on motivation to quit smoking]. / Dépression chez la femme enceinte fumeuse : impact sur la motivation à l'arrêt du tabac.

UNLABELLED: Despite the organization of smoking cessation program, the percentage of pregnant smokers remains too high in France. The knowledge of the factors limiting success of the attempt can help the smoking cessation. AIM: To evaluate the prevalence of depressive disorders in pregnant smokers compared to nonsmokers; assess their impact on motivation stopping smoking; verify their identification can be performed by midwives. MATERIALS AND METHODS: Prospective multicenter survey on 792 women (435 smokers and 357 non-smokers), the assessment of the current depression is made by the Hospital Anxiety Depression scale, and motivation to quit smoking by the Richmond test. RESULTS: Pregnant smokers compared to non-smokers, have more frequent depressive disorders (current: OR=2.4; history: OR=2). These problems do not decrease the motivation to quit, they are associated with a high nicotine dependence and low socioeconomic levels. Their testing can be done by midwives. CONCLUSION: Systematic screening for depression in pregnant women smoking could facilitate smoking cessation.

[Helping the highly dependent smokers]. / Le sevrage tabagique des fumeurs trés dépendants.

Many smokers have difficulty in stopping smoking, either motivated to stop or forced for health, economic or statutory reasons. They have in common a heavy tobacco dependence and a high level of cigarette consumption. Often they combined factors impairing success in the attempt to stop smoking : e. g. anxio-depressive disorders, use of psychoactive substances, socio-economic deprivation. Smoking cessation specialists must optimize their interventions in order to improve the care of these highly dependent smokers.

Intensive mobility training postcerebral hemispherectomy: early surgery shows best functional improvements.

BACKGROUND: Limited research exists on rehabilitative techniques focused on reducing disabilities after cerebral hemispherectomy despite persistent hemiparesis. OBJECTIVES: The efficacy of Intensive Mobility Training (IMT) for improving gait, balance and mobility was evaluated in patients after cerebral hemispherectomy and compared with clinical variables for signs of developmental neuroplasticity. METHODS: Participants (N.=19; 13.8±5.7 years) postcerebral hemispherectomy received IMT, three hours/day for 10 days. Outcomes measures were assessed pre- and post-intervention using the GAITRite electronic walkway® (velocity, toe in/out, step length of affected an unaffected leg), Dynamic Gait Index, Fugl-Meyer Scale, Berg Balance Scale, Timed Up and Go and Six-Minute Walk Test. Six of the nine measures that showed moderate effect sizes were incorporated into a Combined Functional Index (CFI) to assess global impact of therapy. RESULTS: After IMT, improvements were identified for toe in/out, step length of unaffected leg, Dynamic Gait Index, Berg Balance Scale and Six-Minute Walk (P<0.05; Effect Size 0.36-0.50). Using CFI for these six measures, patients improved from 77.3% to 82.7% (+5.3±3.7%) of normal following IMT. Improvements in CFI were greater in patients five years or younger at time of surgery (+7.7±3.6%) compared with older patients (+3.2±2.5%), and this accounted for 22% of variability in the change in score. CONCLUSION: The younger the participant at time of surgery correlated with the greatest improvements following IMT. These findings support the concept that the remaining hemisphere retains greater neuroplasticity if the contralateral surgery occurs earlier in cerebral development.

Removing interictal fast ripples on electrocorticography linked with seizure freedom in children.

BACKGROUND: Fast ripples (FR, 250-500 Hz) detected with chronic intracranial electrodes are proposed biomarkers of epileptogenesis. This study determined whether resection of FR-containing neocortex recorded during intraoperative electrocorticography (ECoG) was associated with postoperative seizure freedom in pediatric patients with mostly extratemporal lesions. METHODS: FRs were retrospectively reviewed in 30 consecutive pediatric cases. ECoGs were recorded at 2,000 Hz sampling rate and visually inspected for FR, with reviewer blinded to the resection and outcome. RESULTS: Average age at surgery was 9.1 ± 6.7 years, ECoG duration was 11.8 ± 8.1 minutes, and postoperative follow-up was 27 ± 4 months. FRs were undetected in 6 ECoGs with remote or extensive lesions. FR episodes (n = 273) were identified in ECoGs from 24 patients, and in 64% FRs were independent of spikes, sharp waves, voltage attenuation, and paroxysmal fast activity. Of these 24 children, FR-containing cortex was removed in 19 and all became seizure-free, including 1 child after a second surgery. The remaining 5 children had incomplete FR resection and all continued with seizures postoperatively. In 2 ECoGs, the location of electrographic seizures matched FR location. FR-containing cortex was found outside of MRI and FDG-PET abnormalities in 6 children. CONCLUSION: FRs were detected during intraoperative ECoG in 80% of pediatric epilepsy cases, and complete resection of FR cortex correlated with postoperative seizure freedom. These findings support the view that interictal FRs are excellent surrogate markers of epileptogenesis, can be recorded during brief ECoG, and could be used to guide future surgical resections in children.

Variable anisotropic brain electrical conductivities in epileptogenic foci.

Source localization models assume brain electrical conductivities are isotropic at about 0.33 S/m. These assumptions have not been confirmed ex vivo in humans. This study determined bidirectional electrical conductivities from pediatric epilepsy surgery patients. Electrical conductivities perpendicular and parallel to the pial surface of neocortex and subcortical white matter (n = 15) were measured using the 4-electrode technique and compared with clinical variables. Mean (+/-SD) electrical conductivities were 0.10 +/- 0.01 S/m, and varied by 243% from patient to patient. Perpendicular and parallel conductivities differed by 45%, and the larger values were perpendicular to the pial surface in 47% and parallel in 40% of patients. A perpendicular principal axis was associated with normal, while isotropy and parallel principal axes were linked with epileptogenic lesions by MRI. Electrical conductivities were decreased in patients with cortical dysplasia compared with non-dysplasia etiologies. The electrical conductivity values of freshly excised human brain tissues were approximately 30% of assumed values, varied by over 200% from patient to patient, and had erratic anisotropic and isotropic shapes if the MRI showed a lesion. Understanding brain electrical conductivity and ways to non-invasively measure them are probably necessary to enhance the ability to localize EEG sources from epilepsy surgery patients.

Improved outcomes in pediatric epilepsy surgery: the UCLA experience, 1986-2008.

OBJECTIVE: Epilepsy neurosurgery is a treatment option for children with refractory epilepsy. Our aim was to determine if outcomes improved over time. METHODS: Pediatric epilepsy surgery patients operated in the first 11 years (1986-1997; pre-1997) were compared with the second 11 years (1998-2008; post-1997) for differences in presurgical and postsurgical variables. RESULTS: Despite similarities in seizure frequency, age at seizure onset, and age at surgery, the post-1997 series had more lobar/focal and fewer multilobar resections, and more patients with tuberous sclerosis complex and fewer cases of nonspecific gliosis compared with the pre-1997 group. Fewer cases had intracranial EEG studies in the post-1997 (0.8%) compared with the pre-1997 group (9%). Compared with the pre-1997 group, the post-1997 series had more seizure-free patients at 0.5 (83%, +16%), 1 (81%, +18%), 2 (77%, +19%), and 5 (74%, +29%) years, and more seizure-free patients were on medications at 0.5 (97%, +6%), 1 (88%, +9%), and 2 (76%, +29%), but not 5 (64%, +8%) years after surgery. There were fewer complications and reoperations in the post-1997 series compared with the pre-1997 group. Logistic regression identified post-1997 series and less aggressive medication withdrawal as the main predictors of becoming seizure-free 2 years after surgery. CONCLUSIONS: Improved technology and surgical procedures along with changes in clinical practice were likely factors linked with enhanced and sustained seizure-free outcomes in the post-1997 series. These findings support the general concept that clearer identification of lesions and complete resection are linked with better outcomes in pediatric epilepsy surgery patients.

Noninvasive testing, early surgery, and seizure freedom in tuberous sclerosis complex.

BACKGROUND: The unambiguous identification of the epileptogenic tubers in individuals with tuberous sclerosis complex (TSC) can be challenging. We assessed whether magnetic source imaging (MSI) and coregistration of (18)fluorodeoxyglucose PET (FDG-PET) with MRI could improve the identification of the epileptogenic regions noninvasively in children with TSC. METHODS: In addition to standard presurgical evaluation, 28 children with intractable epilepsy from TSC referred from 2000 to 2007 had MSI and FDG-PET/MRI coregistration without extraoperative intracranial EEG. RESULTS: Based on the concordance of test results, 18 patients with TSC (64%) underwent surgical resection, with the final resection zone confirmed by intraoperative electrocorticography. Twelve patients are seizure free postoperatively (67%), with an average follow-up of 4.1 years. Younger age at surgery and shorter seizure duration were associated with postoperative seizure freedom. Conversely, older age and longer seizure duration were linked with continued seizures postoperatively or prevented surgery because of nonlateralizing or bilateral independent epileptogenic zones. Complete removal of presurgery MSI dipole clusters correlated with postoperative seizure freedom. CONCLUSIONS: Magnetic source imaging and (18)fluorodeoxyglucose PET/MRI coregistration noninvasively localized the epileptogenic zones in many children with intractable epilepsy from tuberous sclerosis complex (TSC), with 67% seizure free postoperatively. Seizure freedom after surgery correlated with younger age and shorter seizure duration. These findings support the concept that early epilepsy surgery is associated with seizure freedom in children with TSC and intractable epilepsy.

FDG-PET/MRI coregistration improves detection of cortical dysplasia in patients with epilepsy.

OBJECTIVE: Patients with cortical dysplasia (CD) are difficult to treat because the MRI abnormality may be undetectable. This study determined whether fluorodeoxyglucose (FDG)-PET/MRI coregistration enhanced the recognition of CD in epilepsy surgery patients. METHODS: Patients from 2004-2007 in whom FDG-PET/MRI coregistration was a component of the presurgical evaluation were compared with patients from 2000-2003 without this technique. For the 2004-2007 cohort, neuroimaging and clinical variables were compared between patients with mild Palmini type I and severe Palmini type II CD. RESULTS: Compared with the 2000-2003 cohort, from 2004-2007 more CD patients were detected, most had type I CD, and fewer cases required intracranial electrodes. From 2004-2007, 85% of type I CD cases had normal non-University of California, Los Angeles (UCLA) MRI scans. UCLA MRI identified CD in 78% of patients, and 37% of type I CD cases had normal UCLA scans. EEG and neuroimaging findings were concordant in 52% of type I CD patients, compared with 89% of type II CD patients. FDG-PET scans were positive in 71% of CD cases, and type I CD patients had less hypometabolism compared with type II CD patients. Postoperative seizure freedom occurred in 82% of patients, without differences between type I and type II CD cases. CONCLUSIONS: Incorporating fluorodeoxyglucose-PET/MRI coregistration into the multimodality presurgical evaluation enhanced the noninvasive identification and successful surgical treatment of patients with cortical dysplasia (CD), especially for the 33% of patients with nonconcordant findings and those with normal MRI scans from mild type I CD.

Infantile spasm-associated microencephaly in tuberous sclerosis complex and cortical dysplasia.

OBJECTIVE: In children with and without infantile spasms, this study determined brain volumes and cell densities in epilepsy surgery patients with tuberous sclerosis complex (TSC) and cortical dysplasia with balloon cells (CD). METHODS: We compared TSC (n = 18) and CD (n = 17) patients with normal/autopsy controls (n = 20) for MRI gray and white matter volumes and neuronal nuclei (NeuN) cell densities. RESULTS: In patients without a history of infantile spasms, TSC cases showed decreased gray and white matter volumes (-16%). In cases with a history of infantile spasms, both CD (-25%) and TSC (-35%) patients showed microencephaly. This was confirmed in monozygotic twins with TSC, where the twin with a history of spasms had cerebral volumes less (-16%) than the twin without a history of seizures. Regardless of seizure history, TSC patients showed decreased NeuN cell densities in lower gray matter (-36%), whereas CD patients had increased densities in upper cortical (+52%) and white matter regions (+65%). For TSC patients, decreased lower gray matter NeuN densities correlated with reduced MRI volumes. CONCLUSIONS: Patients with tuberous sclerosis without spasms showed microencephaly associated with decreased cortical neuronal densities. In contrast, cortical dysplasia patients without spasms were normocephalic with increased cell densities. This supports the concept that tuberous sclerosis and cortical dysplasia have different pathogenetic mechanisms despite similarities in refractory epilepsy and postnatal histopathology. Furthermore, a history of infantile spasms was associated with reduced cerebral volumes in both cortical dysplasia and tuberous sclerosis patients, suggesting that spasms or their treatment may contribute to microencephaly independent of etiology.

Electrical conductivities of the freshly excised cerebral cortex in epilepsy surgery patients; correlation with pathology, seizure duration, and diffusion tensor imaging.

The electrical conductivities (sigma) of freshly excised neocortex and subcortical white matter were studied in the frequency range of physiological relevance for EEG (5-1005 Hz) in 21 patients (ages 0.67 to 55 years) undergoing epilepsy neurosurgery. Surgical patients were classified as having cortical dysplasia (CD) or non-CD pathologies. Diffusion tensor imaging (DTI) for apparent diffusion coefficient (ADC) and fractional anisotropy (FA) was obtained in 9 patients. Results found that electrical conductivities in freshly excised neocortex vary significantly from patient to patient (sigma = 0.0660-0.156 S/m). Cerebral cortex from CD patients had increased conductivities compared with non-CD cases. In addition, longer seizure durations positively correlated with conductivities for CD tissue, while they negatively correlated for non-CD tissue. DTI ADC eigenvalues inversely correlated with electrical conductivity in CD and non-CD tissue. These results in a small initial cohort indicate that electrical conductivity of freshly excised neocortex from epilepsy surgery patients varies as a consequence of clinical variables, such as underlying pathology and seizure duration, and inversely correlates with DTI ADC values. Understanding how disease affects cortical electrical conductivity and ways to non-invasively measure it, perhaps through DTI, could enhance the ability to localize EEG dipoles and other relevant information in the treatment of epilepsy surgery patients.

Magnetic source imaging localizes epileptogenic zone in children with tuberous sclerosis complex.

The authors assessed whether magnetoencephalography/magnetic source imaging (MEG/MSI) identified epileptogenic zones in patients with tuberous sclerosis complex (TSC). In six TSC children with focal seizures, ictal video-EEG predicted the region of resection with 56% sensitivity, 80% specificity, and 77% accuracy (p = 0.02), whereas interictal MEG/MSI fared better (100%, 94%, and 95%, respectively; p < 0.0001). Interictal MEG/MSI seems to identify epileptogenic zones more accurately in children with TSC and focal intractable epilepsy.

[Chewing tobacco. An emerging habit among adolescents]. / L'utilisation du tabac à chiquer. Une pratique émergente chez les adolescents.

INTRODUCTION: In France, unlike in the United States and Scandinavia, the use of "smokeless tobacco" (also called "chewing tobacco") was rare, but this habit is starting to expand, especially in the world of sports. At ski championships, for example, it is used as a doping agent. Adolescents in mountain areas are now imitating their competitive-skiing peers. CASE: A 16-year-old girl living in a ski resort became addicted to the tobacco paste, "Snuss", and consumed 15-20 doses of Snuss daily, together with a dozen cigarettes. DISCUSSION: "Smokeless tobacco" is emerging as a habit in France, its use encouraged by its discretion, low cost, and rapid induction of addiction. Its growth in Alpine areas requires the urgent development of impact studies to facilitate the organization of information campaigns to treat and prevent its use.

Pediatric cortical dysplasia: correlations between neuroimaging, electrophysiology and location of cytomegalic neurons and balloon cells and glutamate/GABA synaptic circuits.

Seizures in cortical dysplasia (CD) could be from cytomegalic neurons and balloon cells acting as epileptic 'pacemakers', or abnormal neurotransmission. This study examined these hypotheses using in vitro electrophysiological techniques to determine intrinsic membrane properties and spontaneous glutamatergic and GABAergic synaptic activity for normal-pyramidal neurons, cytomegalic neurons and balloon cells from 67 neocortical sites originating from 43 CD patients (ages 0.2-14 years). Magnetic resonance imaging (MRI), (18)fluoro-2-deoxyglucose positron emission tomography (FDG-PET) and electrocorticography graded cortical sample sites from least to worst CD abnormality. Results found that cytomegalic neurons and balloon cells were observed more frequently in areas of severe CD compared with mild or normal CD regions as assessed by FDG-PET/MRI. Cytomegalic neurons (but not balloon cells) correlated with the worst electrocorticography scores. Electrophysiological recordings demonstrated that cytomegalic and normal-pyramidal neurons displayed similar firing properties without intrinsic bursting. By contrast, balloon cells were electrically silent. Normal-pyramidal and cytomegalic neurons displayed decreased spontaneous glutamatergic synaptic activity in areas of severe FDG-PET/MRI abnormalities compared with normal regions, while GABAergic activity was unaltered. In CD, these findings indicate that cytomegalic neurons (but not balloon cells) might contribute to epileptogenesis, but are not likely to be 'pacemaker' cells capable of spontaneous paroxysmal depolarizations. Furthermore, there was more GABA relative to glutamate synaptic neurotransmission in areas of severe CD. Thus, in CD tissue alternate mechanisms of epileptogenesis should be considered, and we suggest that GABAergic synaptic circuits interacting with cytomegalic and normal-pyramidal neurons with immature receptor properties might contribute to seizure generation.

Surgery for symptomatic infant-onset epileptic encephalopathy with and without infantile spasms.

Children undergoing surgery with infant-onset epilepsy were classified into those with medically refractory infantile spasms (IS), successfully treated IS, and no IS history, and the groups were compared for pre- and postsurgery clinical and Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ). Children without an IS history were older at surgery and had longer epilepsy durations than those with IS despite similar substrates, surgeries, and seizure frequencies. In all groups, better postsurgery VABS-DQ scores were associated with early surgical intervention indicating that infant-onset epilepsy patients with or without IS are at risk for seizure-induced encephalopathy.

Cerebral hemispherectomy: hospital course, seizure, developmental, language, and motor outcomes.

OBJECTIVE: To compare hemispherectomy patients with different pathologic substrates for hospital course, seizure, developmental, language, and motor outcomes. METHODS: The authors compared hemispherectomy patients (n = 115) with hemimegalencephaly (HME; n = 16), hemispheric cortical dysplasia (hemi CD; n = 39), Rasmussen encephalitis (RE; n = 21), infarct/ischemia (n = 27), and other/miscellaneous (n = 12) for differences in operative management, postsurgery seizure control, and antiepilepsy drug (AED) usage. In addition, Vineland Adaptive Behavior Scale (VABS) developmental quotients (DQ), language, and motor assessments were performed pre- or postsurgery, or both. RESULTS: Surgically, HME patients had the greatest perioperative blood loss, and the longest surgery time. Fewer HME patients were seizure free or not taking AEDs 1 to 5 years postsurgery, but the differences between pathologic groups were not significant. Postsurgery, 66% of HME patients had little or no language and worse motor scores in the paretic limbs. By contrast, 40 to 50% of hemi CD children showed near normal language and motor assessments, similar to RE and infarct/ischemia cases. VABS DQ scores showed +5 points or more improvement postsurgery in 57% of patients, and hemi CD (+12.7) and HME (+9.1) children showed the most progress compared with RE (+4.6) and infarct/ischemia (-0.6) cases. Postsurgery VABS DQ scores correlated with seizure duration, seizure control, and presurgery DQ scores. CONCLUSIONS: The pathologic substrate predicted pre- and postsurgery differences in outcomes, with hemimegalencephaly (but not hemispheric cortical dysplasia) patients doing worse in several domains. Furthermore, shorter seizure durations, seizure control, and greater presurgery developmental quotients predicted better postsurgery developmental quotients in all patients, irrespective of pathology.

Lobar and multilobar resections for medically intractable pediatric epilepsy.

Pediatric epilepsy surgery patients are different than adult epilepsy surgery patients by having a higher proportion of extratemporal than temporal lobe lesions, and by having cortical dysplasia as the most frequent pathology. We analyzed 111 pediatric epilepsy patients who received lobar or multilobar resections at the University of California, Los Angeles, between the years 1986 and 2000 to determine if there were differences in seizure outcome by lobe of resection and tissue pathology. Results showed that temporal lobe resection patients had lower pre- and postoperative seizure frequencies compared with extratemporal single lobe resection patients (p < 0.05). Furthermore, single lobe resection patients from any brain region had lower pre- and postoperative seizure frequencies compared with multilobar resection patients (p < 0.05), an effect which was due to the better seizure outcomes in temporal lobe resection cases. Patients with mass lesions had the best postoperative seizure control, followed by cortical dysplasia patients and other pathologies (p < 0.05). In all patient groups, there was a significant reduction in pre- to postoperative seizure frequencies (p < 0.0001). These results indicate that postsurgery seizure outcomes in pediatric epilepsy surgery patients vary by lesion location and pathology, with the best outcomes in temporal lobe patients with mass lesions. However, surgical resections of epileptogenic lesions, regardless of lobe, were associated with significant postoperative improvements in seizure frequency.

Spoken language outcomes after hemispherectomy: factoring in etiology.

We analyzed postsurgery linguistic outcomes of 43 hemispherectomy patients operated on at UCLA. We rated spoken language (Spoken Language Rank, SLR) on a scale from 0 (no language) to 6 (mature grammar) and examined the effects of side of resection/damage, age at surgery/seizure onset, seizure control postsurgery, and etiology on language development. Etiology was defined as developmental (cortical dysplasia and prenatal stroke) and acquired pathology (Rasmussen's encephalitis and postnatal stroke). We found that clinical variables were predictive of language outcomes only when they were considered within distinct etiology groups. Specifically, children with developmental etiologies had lower SLRs than those with acquired pathologies (p =.0006); age factors correlated positively with higher SLRs only for children with acquired etiologies (p =.0006); right-sided resections led to higher SLRs only for the acquired group (p =.0008); and postsurgery seizure control correlated positively with SLR only for those with developmental etiologies (p =.0047). We argue that the variables considered are not independent predictors of spoken language outcome posthemispherectomy but should be viewed instead as characteristics of etiology.

Effect of theophylline and trimethobenzamide when given during kainate-induced status epilepticus: an improved histopathologic rat model of human hippocampal sclerosis.

PURPOSE: The most common pathology in temporal lobe epilepsy (TLE) is hippocampal sclerosis. It is controversial whether status epilepticus (SE) or prolonged seizures plus secondary cerebral injuries are pathogenic mechanisms of hippocampal sclerosis. This study addressed this question in rat models of TLE. METHODS: Hippocampal neuron densities and supragranular mossy fiber sprouting were determined in adult rats subjected to systemic kainate-induced SE (KA-only) and KA-induced SE followed 75 minutes later by theophylline (KA/Theo) or trimethobenzamide (KA/Tri). These drugs probably decrease seizure-induced cerebral hyperemia or hypertension. RESULTS: Compared with controls and KA-only rats, KA/Tri and KA/Theo rats showed decreased CA3b and CA1 neuron densities (i.e., greater Sommer's sector injury). In addition, KA/Tri rats showed that increased trimethobenzamide dosages were associated with decreased hilar, CA3c, CA3b, CA1, and subiculum neuron densities. There were no significant differences in supragranular mossy fiber sprouting between KA-only, KA/Tri, and KA/Theo rats. CONCLUSIONS: Pharmacologic manipulations during KA-induced SE are associated with differences in hippocampal pathology, especially in Sommer's sector, and the final pattern of damage and axon sprouting shows histopathologic similarities to that in patients with hippocampal sclerosis. Our findings support the hypothesis that secondary physiologic insults during SE that are likely to decrease seizure-induced cerebral hyperemia and hypertension may generate greater hippocampal neuronal injury compared with SE alone, and this may be a pathogenic mechanism of human hippocampal sclerosis in patients with TLE.