D C Silveira

Barrow Neurological Institute, Phoenix, Arizona, United States

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Publications (38)86.19 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Little is known about the effects of epilepsy surgery on memory in older adults. The purpose of this study was to determine if older adults exhibit greater memory decline than younger adults after anterior temporal lobectomy (ATL). Patients 55 years and older at time of surgery (23 left, 14 right ATL, range 55-66 years) were compared to patients age 25-35 years (44 left, 33 right ATL) to assess differences in preoperative to postoperative change in WMS-III index scores. Repeated-measures ANOVAs and ANCOVAs revealed that older patients did not demonstrate greater decline than younger patients across any of the memory indices. Rather, in the left ATL group, older patients showed less decline than younger patients on the Auditory Delayed Memory Index. Similarly, in the right ATL group, older patients showed less decline than younger patients on the Visual Delayed Memory Index. These patterns were also apparent in frequency of individual change. Results provide preliminary evidence that older adults who are good candidates for ATL are not at greater risk for memory decline when measured at 7 months postoperatively.
    The Clinical Neuropsychologist 10/2013; · 1.68 Impact Factor
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    ABSTRACT: Immunological alterations have been noted following seizures in the acute period, however little is known about the effect of type and severity of epilepsy on leukocyte count in the absence of seizures. We performed a retrospective chart review of adult epilepsy patients presenting for evaluation over a four-month period. Demographics, epilepsy type and characteristics, number and type of antiepileptic drugs, as well as medical co-morbidities were noted. A total of 241 patients fulfilled study criteria. Variables correlating with leukocyte count were identified using univariate analysis. Based on multivariate analysis, only the correlation with type of epilepsy and use of more than two antiepileptic drugs remained statistically significant. Patients with generalised epilepsy had a higher leukocyte count (7.21 k/μL) compared to those with focal epilepsy (6.53 k/μL); the main difference was due to the number of monocytes. These findings raise the possibility that there are different neuro-immune profiles between patients with generalised and focal epilepsy.
    Epileptic disorders: international epilepsy journal with videotape 03/2012; 14(1):57-63. · 0.90 Impact Factor
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    ABSTRACT: The incidence of epilepsy is high in older individuals. However, epilepsy in the elderly may be underdiagnosed and undertreated because of diagnostic difficulties. The main goal of this study was to determine whether seizure semiology differs between older and younger adults with epilepsy in the outpatient setting. Fifty patients with focal epilepsy aged 55 years and older and 50 patients aged between 18 and 45 years were included. Review of medical records contained detailed seizure description. There were no differences in seizure semiology between groups, except that subtle perceptions of transient confusion were seen in older patients but not in younger patients (P=0.0028). Older patients had less generalized motor seizures, but the differences between groups did not reach significance (P=0.01). Older patients may present with subtle symptoms of seizures characterized by brief periods of confusion, which may contribute to greater difficulty diagnosing seizures in the elderly.
    Epilepsy & Behavior 02/2011; 20(2):375-7. · 2.06 Impact Factor
  • Lara E Jehi, Diosely C Silveira, William Bingaman, Imad Najm
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    ABSTRACT: The authors provide a systematic analysis of electroclinical characteristics in patients with persistent seizures following temporal lobe epilepsy (TLE) surgery and identify ideal candidates for reoperation. The authors retrospectively reviewed the records of 68 adult patients (mean follow-up 8.7 years) who underwent a video electroencephalography evaluation and high-resolution imaging after failed TLE surgery performed between 1990 and 2004 at The Cleveland Clinic. Multivariate logistic regression analyses were performed to identify predictors of the yield of a repeat evaluation, location of the recurrence focus, and outcome following reoperation. Although a focus of recurrence was identified in 44 patients, only 15 underwent reoperation, and only 6 of these became seizure free. Localized foci of recurrence were successfully identified in patients with early (within 1 postoperative year) and frequent (≥4 per month) recurrent seizures (yield of 100% if both conditions were fulfilled). Predictors of contiguity of the focus of recurrence to the initial surgical bed were variable depending on the type of the initial surgery: patients with baseline contralateral temporal spiking were 6 times (OR 6.34, p<0.05) more likely to experience seizure recurrence from the contralateral temporal lobe after a "standard" temporal lobectomy, while the need to use subdural electrodes and the timing of recurrence were more significant following limited temporal resections. The focus of recurrence was distant to the original surgical bed when subdural electrodes were used prior to first surgery (OR 28.0, p=0.01) or when seizures recurred early (within <6 postoperative months; OR 12.5, p=0.04). With reoperation, only patients with mesial and basal extension of the temporal resections became seizure free. Interestingly, seizure freedom was achieved with medical therapy alone in 42% of patients with a nonidentifiable recurrence focus as opposed to 4% of those with an unoperated identifiable focus. The timing and frequency of recurrent seizures following unsuccessful TLE surgery provide useful guidelines for the yield of a surgical reevaluation, and potentially for the mechanisms of surgical failure.
    Journal of Neurosurgery 12/2010; 113(6):1186-94. · 3.15 Impact Factor
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    ABSTRACT: Recent studies suggest a potential relationship between Restless Legs Syndrome (RLS) and hypertension and heart disease. Acute clinical stroke has been linked to the immediate onset of RLS, and epidemiological studies suggest the possibility that RLS may also lead to stroke. MRI scans from 26 RLS cases and 241 controls from the population based MEMO-Study (Memory and Morbidity in Augsburg Elderly) were assessed for the presence of clinical stroke, silent infarction, subcortical lesions and cortical atrophy. T1, T2, proton density images were obtained and infarcts and their characteristics were determined by visual inspection. RLS status was assessed according to the minimal criteria of the International RLS Study Group. Scans from the 26 RLS patients and a subset of 26 age and sex matched controls were reexamined by a separate rater using the same methodology. Descriptive statistics, logistic and linear regression models were used to determine the risk of the three types of CNS changes associated with RLS case status. Among the 267 participants there was no difference in the prevalence of cardiovascular diseases or risk factors between RLS patients and the 241 controls. The prevalences of cerebrovascular events of all types, were greater in RLS patients, as were the amounts of cortical atrophy and the volume of subcortical lesions. However, these differences were not statistically significant. When age, sex and co-morbidities were taken into account in a logistic regression model, there was a statistically non-significant greater risk for stroke (Odds Ratio 2.46 with 95% CI 0.97-6.28, p = .06) associated with RLS case status. Future similar studies need to be performed on younger patients without other potential vascular risk factors, using Flair images and computerized programs for detection of cerebral ischemia. Improved methods for detection may allow for a reasonable sample size.
    The Open Neurology Journal 01/2010; 4:73-7.
  • Cerebrovascular Diseases 02/2007; 24(6):543-4. · 3.70 Impact Factor
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    ABSTRACT: It is known that evoked seizures can increase neurogenesis in the dentate gyrus in adult rats. Whether spontaneous seizures occurring after status epilepticus (SE) also results in alterations in neurogenesis is not known. Here, we measured neurogenesis in rats with and without spontaneous seizures following SE. Lithium-pilocarpine was used to induce seizures in postnatal (P) day 20 rats. Spontaneous seizure frequency was assessed 2 months using video monitoring. Rats then received bromodeoxyuridine to label dividing DNA and were sacrificed 24 h later. Animals with spontaneous seizures (n = 9) had a modest increase in neurogenesis compared to animals with SE (n = 6) and no spontaneous seizures and control rats (n = 10). These findings demonstrate that the hippocampus is capable of generating new neurons weeks following SE and further that recurrent seizures enhance the production of new neurons. These alterations in neurogenesis may contribute to ongoing pathological changes week and months following SE.
    Brain and Development 10/2004; 26(6):394-7. · 1.54 Impact Factor
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    ABSTRACT: Networks of GABAergic interneurons are of utmost importance in generating and promoting synchronous activity and are involved in producing coherent oscillations. These neurons are characterized by their fast-spiking rate and by the expression of the Ca(2+)-binding protein parvalbumin (PV). Alteration of their inhibitory activity has been proposed as a major mechanism leading to epileptic seizures and thus the role of PV in maintaining the stability of neuronal networks was assessed in knockout (PV-/-) mice. Pentylenetetrazole induced generalized tonic-clonic seizures in all genotypes, but the severity of seizures was significantly greater in PV-/- than in PV+/+ animals. Extracellular single-unit activity recorded from over 1000 neurons in vivo in the temporal cortex revealed an increase of units firing regularly and a decrease of cells firing in bursts. In the hippocampus, PV deficiency facilitated the GABA(A)ergic current reversal induced by high-frequency stimulation, a mechanism implied in the generation of epileptic activity. We postulate that PV plays a key role in the regulation of local inhibitory effects exerted by GABAergic interneurons on pyramidal neurons. Through an increase in inhibition, the absence of PV facilitates synchronous activity in the cortex and facilitates hypersynchrony through the depolarizing action of GABA in the hippocampus.
    Molecular and Cellular Neuroscience 05/2004; 25(4):650-63. · 3.73 Impact Factor
  • Diosely C Silveira, Byung Ho Cha, Gregory L Holmes
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    ABSTRACT: The cholinergic system modulates cerebral excitability. We recently reported that immunolesions of the basal forebrain (BF) cholinergic neurons in adult rats increase the susceptibility to generalized seizures. In this study we investigated the effects of lesions of the BF cholinergic neurons in neonatal rats on seizure susceptibility and cognitive function. Neonatal rats at postnatal day (P) 7 received intracerebroventricular (i.c.v.) injections of 192 IgG-saporin (SAP) or phosphate-buffered saline. Following 3 weeks after the injection the first group of rats was implanted with hippocampal electrodes for electroencephalogram (EEG) recordings while the second group of rats was tested for visual spatial memory using the hidden platform version of the water maze test. The first group of rats was then tested for seizure susceptibility using flurothyl 1 week after the electrode implantation. Rats that received immunolesions of the BF cholinergic neurons at P7 had significantly shorter latencies to onset of myoclonic jerks and tonic-clonic seizures than controls. However, no significant differences were found in the duration of seizures, or EEG ictal duration. No significant deficits in spatial learning were found between rats that received i.c.v. injections of SAP at P7 and controls. As in adult rats, lesions of the BF cholinergic system in rat pups result in subsequent increase in seizure susceptibility.
    Developmental Brain Research 01/2003; 139(2):277-83. · 1.78 Impact Factor
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    ABSTRACT: There is increasing evidence that enriching the environment can improve cognitive and motor deficits following a variety of brain injuries. Whether environmental enrichment can improve cognitive impairment following status epilepticus (SE) is not known. To determine whether the environment in which animals are raised influences cognitive function in normal rats and rats subjected to SE. Rats (n = 100) underwent lithium-pilocarpine-induced SE at postnatal (P) day 20 and were then placed in either an enriched environment consisting of a large play area with toys, climbing objects, and music, or in standard vivarium cages for 30 days. Control rats (n = 32) were handled similarly to the SE rats but received saline injections instead of lithium-pilocarpine. Rats were then tested in the water maze, a measure of visual-spatial memory. A subset of the rats were killed during exposure to the enriched or nonenriched environment and the brains examined for dentate granule cell neurogenesis using bromodeoxyuridine (BrdU) and phosphorylated cyclic AMP response element binding protein (pCREB) immunostaining, a brain transcription factor important in long-term memory. Both control and SE rats exposed to the enriched environment performed significantly better than the nonenriched group in the water maze. There was a significant increase in neurogenesis and pCREB immunostaining in the dentate gyrus in both control and SE animals exposed to the enriched environment compared to the nonenriched groups. Environmental enrichment resulted in no change in SE-induced histologic damage. Exposure to an enriched environment in weanling rats significantly improves visual-spatial learning. Even following SE, an enriched environment enhances cognitive function. An increase in neurogenesis and activation of transcription factors may contribute to this enhanced visual-spatial memory.
    Neurology 12/2002; 59(9):1356-64. · 8.30 Impact Factor
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    ABSTRACT: Topiramate, an antiepileptic drug with a number of mechanisms of action including inhibition of glutamate activity at the AMPA and KA receptors, was assessed as a neuroprotective agent following seizures. We administered topiramate, 80 mg/kg, or saline for 4 weeks following a series of 25 neonatal seizures or status epilepticus (SE) induced by lithium-pilocarpine in postnatal day 20 rats. Age-matched control rats without a history of seizures were administered topiramate or saline. Following completion of the topiramate injections, animals were tested in the water maze for spatial learning and the brains examined for cell loss and sprouting of mossy fibers. While there was a trend for improved visual-spatial performance in the water maze following topiramate therapy in rats with neonatal seizures, no differences were found in the histological examination of the hippocampus. Neonatal rats exposed to 4 weeks of topiramate did not differ from non-treated controls in water maze performance or histological examination. In weanling rats subjected to SE, topiramate provided a moderate degree of neuroprotection, with topiramate-treated rats performing better in the water maze than rats receiving saline. However, no differences in cell loss or mossy fiber sprouting were found in the histological examination of the brains. These findings demonstrate that chronic treatment with topiramate following SE improves cognitive function. In addition, long-term administration of high-dose topiramate in the normal developing rat brain does not appear to impair cognitive performance.
    Epilepsy Research 11/2002; 51(3):217-32. · 2.19 Impact Factor
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    ABSTRACT: Status epilepticus (SE) has a high mortality and morbidity rate in children. Disturbances in learning and memory are frequently associated with SE although it is not clear when the cognitive deficits occur. If cognitive dysfunction occurs immediately following the seizure, the window of opportunity for therapeutic intervention is limited. The first goal of this study was to determine the timing of cognitive dysfunction following SE in weanling rats. As there is evidence that enriching the environment can improve cognitive and motor deficits following brain injury, our second goal was to determine whether environmental enrichment improves cognitive function following SE. Rats underwent lithium-pilocarpine-induced SE at postnatal (P) day 20 and were then tested for visual-spatial memory in the water maze at P22, P25, P30, or P50. Rats with SE performed significantly worse in the water maze than control rats at all time points. Once the time-courses of visual-spatial memory deficits were determined, a second group of P20 rats were subjected to SE and were then placed in an enriched environment (enriched group) or remained in standard cages in the vivarium (nonenriched group) for 28 days. Following environmental manipulation, the animals were tested in the water maze. Rats housed in an enriched environment following the SE performed substantially better in the water maze than rats housed in standard cages. However, no differences were found between the enriched and nonenriched groups in EEG or histological evaluation. Although SE results in cognitive impairment within days of the seizure, housing in an enriched environment after SE has a beneficial effect on cognitive performance in rats.
    European Journal of Neuroscience 09/2002; 16(3):501-13. · 3.67 Impact Factor
  • Diosely C Silveira, Yoshimi Sogawa, Gregory L Holmes
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    ABSTRACT: The expression of limbic seizures following kainic acid (KA) administration starts at approximately postnatal day (P) 19 in rats. In this study we investigated whether the expression of Fos-like immunoreactivity (Fos-IR) in limbic regions occurs concomitantly with the behavioural expression of limbic seizures. Immunohistochemistry for c-Fos protein was examined 1, 2, 4, 12 and 24 h following seizure onset (KA-treated rats) or saline injections (controls) in immature and adult rats at P7, P13, P20 and P60. The expression of Fos-IR in limbic structures following KA-induced seizures is age-dependent. There is a strong and selective induction of Fos-IR in the CA3 region of the hippocampus following KA-induced seizures in rats at P7. However, the expression of Fos-IR in KA-treated rats at P13, P20 and P60 involved other hippocampal structures in addition to CA3. Abundant induction of Fos-IR was found in the CA1, CA3 and dentate gyrus (DG) in KA-treated rats at P13, P20 and P60. While immature rats at P7 and P13 showed very few or no Fos-IR neurons in most amygdala nuclei, rat pups at P20 showed strong induction of Fos-IR in the amygdala. Our results demonstrated that the induction of Fos-IR in most amygdala nuclei and the full expression of behavioural limbic seizures occur at the same developmental age, which is consistent with the idea that the amygdala may play a role in the modulation of limbic seizures.
    European Journal of Neuroscience 02/2002; 15(2):329-44. · 3.67 Impact Factor
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    ABSTRACT: Neonatal seizures are frequently associated with cognitive impairment and reduced seizure threshold. Previous studies in our laboratory have demonstrated that rats with recurrent neonatal seizures have impaired learning, lower seizure thresholds, and sprouting of mossy fibers in CA3 and the supragranular region of the dentate gyrus in the hippocampus when studied as adults. The goal of this study was to determine the age of onset of cognitive dysfunction and alterations in seizure susceptibility in rats subjected to recurrent neonatal seizures and the relation of this cognitive impairment to mossy fiber sprouting and expression of glutamate receptors. Starting at postnatal day (P) 0, rats were exposed to 45 flurothyl-induced seizures over a 9-day period of time. Visual-spatial learning in the water maze and seizure susceptibility were assessed in subsets of the rats at P20 or P35. Brains were evaluated for cell loss, mossy fiber distribution, and AMPA (GluR1) and NMDA (NMDAR1) subreceptor expression at these same time points. Rats with neonatal seizures showed significant impairment in the performance of the water maze and increased seizure susceptibility at both P20 and P35. Sprouting of mossy fibers into the CA3 and supragranular region of the dentate gyrus was seen at both P20 and P35. GluR1 expression was increased in CA3 at P20 and NMDAR1 was increased in expression in CA3 and the supragranular region of the dentate gyrus at P35. Our findings indicate that altered seizure susceptibility and cognitive impairment occurs prior to weaning following a series of neonatal seizures. Furthermore, these alterations in cognition and seizure susceptibility are paralleled by sprouting of mossy fibers and increased expression of glutamate receptors. To be effective, our results suggest that strategies to alter the adverse outcome following neonatal seizures will have to be initiated during, or shortly following, the seizures.
    Developmental Brain Research 12/2001; 131(1-2):73-83. · 1.78 Impact Factor
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    ABSTRACT: Seizures in preterm infants are associated with a high risk of neurological sequelae. In the neonatal rat recurrent seizures have been associated with long-term changes in cerebral excitability and cognition as well as sprouting of mossy fiber terminals in the granule cell layer of the dentate gyrus and hippocampal CA3 subfield. To evaluate the relationship between seizure-induced morphological changes and cognitive function we subjected newborn rats to 55 seizures with flurothyl during the first 12 days of life. During adolescence rats with prior recurrent seizures were compared with controls in electroencephalographic power and performance in the Morris water maze and open field test. Rats subjected to recurrent seizures had marked impairment in water maze performance and never reached the level of learning seen in controls despite a total of 54 trials. Recurrent seizures were also associated with an overall reduction in spectral power which was most pronounced in the theta range. On histological examination rats with recurrent neonatal seizures had sprouting of mossy fiber terminals in CA3 and the granule cell layer of the dentate gyrus without any accompanying cell loss. Sprouting in CA3, but not the granule cell layer of the dentate gyrus, correlated with water maze performance. This study demonstrates that recurrent neonatal seizures can result in profound impairment of water maze performance and reduction of electroencephalographic power despite the lack of discernible cell loss and that this cognitive impairment correlates with mossy fiber sprouting in CA3.
    Developmental Brain Research 08/2001; 129(1):27-38. · 1.78 Impact Factor
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    Developmental Brain Research 06/2001; 128(2):197. · 1.78 Impact Factor
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    ABSTRACT: Although neonatal seizures are quite common, there is controversy regarding their consequences. Despite considerable evidence that seizures may cause less cell loss in young animals compared with mature animals, there are nonetheless clear indications that seizures may have other potentially deleterious effects. Because it is known that seizures in the mature brain can increase neurogenesis in the hippocampus, we studied the extent of neurogenesis in the granule cell layer of the dentate gyrus over multiple time points after a series of 25 flurothyl-induced seizures administered between postnatal day 0 (P0) and P4. Rats with neonatal seizures had a significant reduction in the number of the thymidine analog 5-bromo-2'-deoxyuridine-5'-monophosphate- (BrdU) labeled cells in the dentate gyrus and hilus compared with the control groups when the animals were killed either 36 hr or 2 weeks after the BrdU injections. The reduction in BrdU-labeled cells continued for 6 d after the last seizure. BrdU-labeled cells primarily colocalized with the neuronal marker neuron-specific nuclear protein and rarely colocalized with the glial cell marker glial fibrillary acidic protein, providing evidence that a very large percentage of the newly formed cells were neurons. Immature rats subjected to a single seizure did not differ from controls in number of BrdU-labeled cells. In comparison, adult rats undergoing a series of 25 flurothyl-induced seizures had a significant increase in neurogenesis compared with controls. This study indicates that, after recurrent seizures in the neonatal rat, there is a reduction in newly born granule cells.
    Journal of Neuroscience 04/2001; 21(6):2094-103. · 6.75 Impact Factor
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    ABSTRACT: The purpose of this study was to compare the serum levels of androgens between hyposexual and non-hyposexual patients with epilepsy. Adult male patients with epilepsy were investigated. Serum levels of testosterone (T) and free-T, estradiol, and sex hormone binding globulin (SHBG) were measured and the free androgen index (FAI) was calculated. While there were no differences between hyposexual and non-hyposexual patients in the serum levels of T, free-T, and estradiol, or to the FAI, the serum levels of SHBG were significantly higher in hyposexual patients than in non-hyposexual patients. Thus, the effects of increased SHBG upon serum levels of testosterone biologically active in patients with epilepsy and hyposexuality were not detected by the methods used in this study. Four (44%) of nine hyposexual patients who were re-evaluated after two years follow-up improved sexual performance. Thus, clinical treatment that results in good seizure control may improve sexual performance in some patients with epilepsy.
    Arquivos de Neuro-Psiquiatria 04/2001; 59(1):23-8. · 1.01 Impact Factor
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    ABSTRACT: Following kainic acid (KA)-induced status epilepticus (SE), the ketogenic diet (KD) retards the development of epileptogenesis, with fewer spontaneous recurrent seizures (SRS) and less mossy fiber sprouting than rats on a normal diet. In this study, we investigated whether there is a critical period for initiation of the KD, in terms of the diet's effectiveness in reducing SRS. In addition, we investigated whether early treatment with the KD prevents the deficits in spatial learning and memory that ordinarily follow KA-induced SE. Young rats (P30) underwent KA-induced SE, followed by assignment to one of three treatment groups: control diet ('KA'), KD begun 2 days after SE ('KD2'), and KD begun fourteen days after SE ('KD14'). For 12 weeks following SE, rats were monitored by closed circuit video recording (12 h/wk) to detect SRS. KD2 rats had significantly fewer SRS than rats in the control or KD14 groups. On water maze testing to assess spatial learning and memory, KD2 rats had significantly poorer acquisition of place learning than control (KA alone) or KD14 rats. KD2 rats also failed to gain weight well. There was no difference between groups on routine histologic examination of the hippocampus. In summary, P30 rats placed on the KD 2 days after SE were relatively protected from recurrent seizures, but showed behavioral and physical impairment. Rats placed on the KD 14 days after KA-induced SE did not differ from controls with regard to spontaneous seizure rate.
    Developmental Brain Research 01/2001; 125(1-2):131-8. · 1.78 Impact Factor
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    ABSTRACT: We investigated whether basal forebrain cholinergic neurons influence the expression of generalized seizures. Animals received intracerebroventricular injections of saporin (lesioned) or saline (controls) and were tested for susceptibility to flurothyl- or pentylenetetrazole-induced seizures. Lesioned rats had significantly shorter latencies to onset of generalized tonic-clonic seizures than controls. Our findings suggest that basal forebrain cholinergic neurons may participate in the modulation of generalized seizures.
    Brain Research 10/2000; 878(1-2):223-7. · 2.83 Impact Factor

Publication Stats

867 Citations
86.19 Total Impact Points


  • 2010
    • Barrow Neurological Institute
      • Department of Neurosurgery
      Phoenix, Arizona, United States
    • Cleveland Clinic
      • Department of Neuroradiology
      Cleveland, OH, United States
  • 2002–2004
    • Boston Children's Hospital
      • Department of Neurology
      Boston, MA, United States
  • 1999–2003
    • Harvard Medical School
      • Department of Neurology
      Boston, MA, United States
  • 1998–2000
    • Beth Israel Deaconess Medical Center
      • Department of Neurology
      Boston, MA, United States
  • 1992–2000
    • University of Campinas
      • • Faculdade de Ciências Médicas (FCM)
      • • Departamento de Neurologia
      Campinas, Estado de Sao Paulo, Brazil