Gabriela Novak

Publications

• 0.86

  Impact points

  Exposure to nicotine produces an increase in dopamine D2(High) receptors: a possible mechanism for dopamine hypersensitivity.

  Gabriela Novak, Philip Seeman, Bernard Le Foll

  The International journal of neuroscience. 11/2010; 120(11):691-7.

  Dopamine D2 receptors exist in both low- and high-affinity states (D2(High)), the latter being the functionally relevant state. Cocaine self-administration produces an increase in D2(High), a phenomenon that could explain why cocaine administration results in hypersensitivity to dopamine, even thoug... [more] Dopamine D2 receptors exist in both low- and high-affinity states (D2(High)), the latter being the functionally relevant state. Cocaine self-administration produces an increase in D2(High), a phenomenon that could explain why cocaine administration results in hypersensitivity to dopamine, even though drug addicts were found to have a decreased number of striatal dopamine D2 receptors. As nicotine acts through the same mesocortical dopaminergic signaling pathways as other stimulant drugs, which are known to increase the levels of D2(High), we hypothesized that nicotine exposure could produce an increase in D2(High) levels. We determined D2(High) levels in rats after nicotine administration (1.5 mg/kg/day; 14 days), in rats voluntarily self-administering nicotine using an intravenous self-administration (IVSA) protocol (mean dose 0.5 mg/kg/day; 14 days), as well as after a prolonged withdrawal. An increase in the levels of D2(High) was found in rats who had nicotine administered at a uniform dose, as well as in rats who self-administered nicotine via IVSA, but these changes appear to normalize over time, as indicated by lower D2(High) levels in rats after a prolonged withdrawal period. We suggest that nicotine-induced elevation in D2(High) levels could be participating in hypersensitivity to dopamine following nicotine exposure.
• 8.93

  Impact points

  The 2nd Schizophrenia International Research Society Conference, 10-14 April 2010, Florence, Italy: summaries of oral sessions.

  Moogeh Baharnoori, Cali Bartholomeusz, Aurelie A Boucher, Lisa Buchy, Christopher Chaddock, Bonga Chiliza, Melanie Föcking, Alex Fornito, Juan A Gallego, Hiroaki Hori, [......], Naren P Rao, Igor Riecansky, Darryl C Smith, Renan P Souza, Renate Thienel, Hanan D Trotman, Hiroyuki Uchida, Kristen A Woodberry, Anne O'Shea, Lynn E DeLisi

  Schizophrenia research. 10/2010; 124(1-3):e1-62.

  The 2nd Schizophrenia International Research Society Conference, was held in Florence, Italy, April 10-15, 2010. Student travel awardees served as rapporteurs of each oral session and focused their summaries on the most significant findings that emerged from each session and the discussions that fol... [more] The 2nd Schizophrenia International Research Society Conference, was held in Florence, Italy, April 10-15, 2010. Student travel awardees served as rapporteurs of each oral session and focused their summaries on the most significant findings that emerged from each session and the discussions that followed. The following report is a composite of these reviews. It is hoped that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.

• Hyperactive mice show elevated D2High receptors, a model for schizophrenia: calcium/calmodulin-dependent kinase II alpha knockouts.

  G. Novak, P. Seeman

  2nd Biennial Schizophrenia International Research Conference., Florence, Italy; 04/2010
• 2.15

  Impact points

  Association of polymorphisms in the BDNF, DRD1 and DRD3 genes with tobacco smoking in schizophrenia.

  Gabriela Novak, Martha LeBlanc, Clement Zai, Sajid Shaikh, Julien Renou, Vincenzo DeLuca, Natalie Bulgin, James L Kennedy, Bernard Le Foll

  Annals of human genetics. 04/2010; 74(4):291-8.

  Emerging evidence indicates that the DRD1-BDNF-DRD3 cluster plays an important role in nicotine addiction. We have performed an association analysis of 42 SNPs within these genes with cigarette consumption in a group of 341 schizophrenia patients. The ACCG haplotype consisting of four BDNF markers (... [more] Emerging evidence indicates that the DRD1-BDNF-DRD3 cluster plays an important role in nicotine addiction. We have performed an association analysis of 42 SNPs within these genes with cigarette consumption in a group of 341 schizophrenia patients. The ACCG haplotype consisting of four BDNF markers (Val66Met (rs6265), rs11030104, rs2049045 and rs7103411) showed an association with the risk of smoking (p = 0.0002). Both DRD1 markers tested (rs4532 and rs686) and the DRD3 marker (rs1025398) showed association with quantity of tobacco smoked (p = 0.01, 0.005 and 0.002, respectively). Our findings are preliminary; however, they support the involvement of the DRD1, BDNF and DRD3 genes in smoking behaviour.
• 2.56

  Impact points

  Hyperactive mice show elevated D2(High) receptors, a model for schizophrenia: Calcium/calmodulin-dependent kinase II alpha knockouts.

  Gabriela Novak, Philip Seeman

  Synapse (New York, N.Y.). 03/2010; 64(10):794-800.

  The cerebral frontal cortex of patients who had schizophrenia shows elevated levels of RNA for calcium/calmodulin-dependent protein kinase II beta (CaMKIIbeta). In addition, recent research shows that animal models for schizophrenia, such as amphetamine-sensitized rats, consistently show elevated le... [more] The cerebral frontal cortex of patients who had schizophrenia shows elevated levels of RNA for calcium/calmodulin-dependent protein kinase II beta (CaMKIIbeta). In addition, recent research shows that animal models for schizophrenia, such as amphetamine-sensitized rats, consistently show elevated levels of D2 receptors in their high-affinity state (D2(High)), the major target for antipsychotic medication. The present study was done, therefore, to examine whether an alteration in the levels of CaMKIIbeta could lead to altered levels of D2(High) receptors. We found that the CaMKII inhibitor, KN-93, markedly reduced D2(High) states in rat striatum. In addition, we studied heterozygous CaMKIIalpha knock-out mice that show features analogous to schizophrenia. The striata of these mice revealed a 2.8-fold increase in D2(High) receptors. In frontal cortex of the heterozygous CaMKIIalpha knock-out mice, CaMKIIalpha mRNA levels were reduced by 50%, while CaMKIIbeta mRNA levels were unaltered. In striatum, CaMKIIbeta mRNA levels were increased by 29%, suggesting the presence of a new CaMKIIbeta regulatory pathway not previously described. The elevated levels of CaMKIIbeta mRNA in the striatum suggest that this enzyme may increase D2(High) in animals and possibly in schizophrenia itself.

• Replicated association of the NR4A3 gene with smoking behavior in schizophrenia and in bipolar disorder.

  Gabriela Novak, Cement C. Zai, Moniba Mirkhani, Sajid Shaikh, John B. Vincent, Herbert Y Meltzer, Jeffrey A Lieberman, John Strauss, Daniel Lévesque, James L. Kennedy, Bernard Le Foll

  Genes, Brain and Behaviour. 01/2010;

  Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a ... [more] Schizophrenia and bipolar disorder are associated with dopamine neurotransmission and show high comorbidity with tobacco dependence. Recent evidence indicates that the family of the NR4A orphan nuclear receptors, which are expressed in dopamine neurons and in dopaminoceptive brain areas, may play a role in dopamine-mediated effects. We have, therefore, analyzed the association of six SNP's within the three genes belonging to the NR4A orphan nuclear receptor family, NR4A1 (rs2603751, rs2701124), NR4A2 (rs12803, rs834835) and NR4A3 (rs1131339, rs1405209), with the degree of smoking in a sample of 204 unrelated schizophrenia patients, which included 126 smokers and 78 non-smokers. SNPs within the NR4A3 gene (rs1131339 and rs1405209) were significantly associated with heavy smoking in this cohort, using a stepwise analysis of the escalated number of cigarettes smoked per day (p=0.008 and 0.006, respectively; satisfying the Nyholt significance threshold of 0.009, an adjustment for multiple testing). We then repeated the association analysis of the NR4A3 markers (rs1131339 and rs1405209) in a larger cohort of 319 patients with bipolar disorder, which included 167 smokers and 152 non-smokers. We have replicated the positive association with smoking of the NR4A3 SNP rs1131339 in this group (p=0.04), providing an important confirmation of the involvement of the NR4A3 gene in nicotine addiction in patients with mental health disease, a population significantly at risk for nicotine addiction. PMID: 20659174

• Exposure to nicotine produces an increase in dopamine D2High receptors: a possible mechanism for dopamine hypersensitivity.

  Gabriela Novak, Philip Seeman, Bernard Le Foll

  The International Journal of Neuroscience. 01/2010;

  Dopamine D2 receptors exist in both a low and a high affinity state (D2High), the latter being the functionally relevant state. Cocaine self-administration produces an increase in D2High, a phenomenon that could explain why cocaine administration results in a hypersensitivity to dopamine, even thoug... [more] Dopamine D2 receptors exist in both a low and a high affinity state (D2High), the latter being the functionally relevant state. Cocaine self-administration produces an increase in D2High, a phenomenon that could explain why cocaine administration results in a hypersensitivity to dopamine, even though drug addicts were found to have a decreased number of striatal dopamine D2 receptors. Since nicotine acts through the same mesocortical dopaminergic signaling pathways as other stimulant drugs, which are known to increase the levels of D2High, we hypothesized that nicotine exposure could produce an increase in D2High levels. We determined D2High levels in rats after nicotine administration (1.5 mg/kg/day; 14 days), in rats voluntarily self-administering nicotine using an intravenous self-administration (IVSA) protocol (mean dose 0.5 mg/kg/day; 14 days), as well as after a prolonged withdrawal. An increase in the levels of D2High was found in rats who had nicotine administered at a uniform dose, as well as in rats who self-administered nicotine via IVSA, but these changes appear to normalize over time, as indicated by lower D2High levels in rats after a prolonged withdrawal period. We suggest that nicotine-induced elevation in D2High levels could be participating in hypersensitivity to dopamine following nicotine exposure.
• 2.33

  Impact points

  Association of the orphan nuclear receptor NR4A1 with tardive dyskinesia.

  Gabriela Novak, Alexandra Gallo, Clement C Zai, Herbert Y Meltzer, Jeffrey A Lieberman, Steven G Potkin, Aristotle N Voineskos, Gary Remington, James L Kennedy, Daniel Levesque, Bernard Le Foll

  Psychiatric genetics. 12/2009;

  Recent evidence has identified the NR4A1 (NUR77, NGFI-B) gene as a strong candidate for involvement in tardive dyskinesia (TD). We have investigated the association of six single nucleotide polymorphisms within the NR4A family of genes with TD in a sample of 171 patients with schizophrenia of Caucas... [more] Recent evidence has identified the NR4A1 (NUR77, NGFI-B) gene as a strong candidate for involvement in tardive dyskinesia (TD). We have investigated the association of six single nucleotide polymorphisms within the NR4A family of genes with TD in a sample of 171 patients with schizophrenia of Caucasian descent. The NR4A1 single nucleotide polymorphism (SNP) marker rs2603751 showed a nominal association with the risk of TD, as well as with the extent of TD based on the Abnormal Involuntary Movements Scale (AIMS) scores. The haplotype generated by the markers rs2603751 and rs2701124 also showed association with TD and, after adjustment for multiple testing, both the NR4A1 marker rs2603751 and the haplotype continued to show a trend toward association with TD. Although the results of this study are limited by a small sample size, it presents important pilot data and warrants further investigation of the involvement of NR4A1 variants in TD.
• 5.56

  Impact points

  Association of a polymorphism in the NRXN3 gene with the degree of smoking in schizophrenia: A preliminary study.

  Gabriela Novak, Julien Boukhadra, Sajid Shaikh, James Kennedy, Bernard Le Foll

  The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. 09/2009;

  Whole genome scan studies have recently identified the NRXN1 and NRXN3 genes as potential contributing factors in the risk for nicotine addiction. We have genotyped 15 single nucleotide polymorphisms (SNPs) spanning the NRXN1 and NRXN3 genes in 195 unrelated patients with schizophrenia for whom info... [more] Whole genome scan studies have recently identified the NRXN1 and NRXN3 genes as potential contributing factors in the risk for nicotine addiction. We have genotyped 15 single nucleotide polymorphisms (SNPs) spanning the NRXN1 and NRXN3 genes in 195 unrelated patients with schizophrenia for whom information about their smoking status and number of cigarettes smoked per day (CPD) was obtained. The NRXN3 marker rs1004212 was significantly associated with quantity of tobacco smoked. Individuals homozygous for the C allele of rs1004212 smoked more cigarettes per day than heterozygous individuals. We found no significant association of markers within the NRXN1 gene with the risk of smoking or the quantity of tobacco smoked. Because of the relatively small sample size, this is a preliminary study. However, this candidate gene study supports the observations of molecular studies implicating the NRXN genes in drug addiction and suggests that variants in the NRXN3 gene could contribute to the degree of nicotine dependence in patients with schizophrenia.

• Upregulation of CaMKIIβ and Nogo-C mRNA in schizophrenia and the prevalence of CAA insert in the 3’UTR of the Nogo gene.

  Gabriela Novak

  01/2008

  Degree: Ph.D.

  Supervisor: Dr. Philip Seeman

  Download Paper
• 2.56

  Impact points

  Amphetamine sensitization elevates CaMKIIbeta mRNA.

  Rachel Greenstein, Gabriela Novak, Philip Seeman

  Synapse (New York, N.Y.). 11/2007; 61(10):827-34.

  Recent studies have shown that the elevation in calcium/calmodulin-dependent protein kinase II (CaMKII) may play an important role in amphetamine-induced dopamine release, as well as in the increase of dopamine D2 receptor high-affinitystates in psychosis. Because amphetamine sensitization is a wide... [more] Recent studies have shown that the elevation in calcium/calmodulin-dependent protein kinase II (CaMKII) may play an important role in amphetamine-induced dopamine release, as well as in the increase of dopamine D2 receptor high-affinitystates in psychosis. Because amphetamine sensitization is a widely used animal model of psychosis or schizophrenia, we investigated whether amphetamine sensitization results in an overall increase in the alpha and beta subunits of CaMKII. To answer this question, we measured CaMKII alpha and beta subunit mRNA expression using Real-Time Quantitative PCR in amphetamine-sensitized rat striata, compared to saline-treated controls. The results were then standardized to beta-glucuronidase, a housekeeping gene. Our results showed a statistically significant increase in the CaMKII beta subunit, and an increase in the alpha subunit which did not reach statistical significance. Because the levels of both CaMKIIbeta and CaMKIIalpha play a role in neuronal function and synapse formation, the present finding of an elevated level of CaMKII beta and alpha subunit mRNA in the amphetamine-sensitized model of psychosis points to the possibility of dysregulated levels of CaMKII subunits in human psychosis.
• 2.46

  Impact points

  Nogo A, B and C expression in schizophrenia, depression and bipolar frontal cortex, and correlation of Nogo expression with CAA/TATC polymorphism in 3'-UTR.

  Gabriela Novak, Teresa Tallerico

  Brain research. 12/2006; 1120(1):161-71.

  Schizophrenia may result from altered gene expression leading to abnormal neurodevelopment. In a search for genes with altered expression in schizophrenia, our previous work on human frontal cerebral cortex found the mRNA of Nogo, a myelin-associated protein which inhibits the outgrowth of neurites ... [more] Schizophrenia may result from altered gene expression leading to abnormal neurodevelopment. In a search for genes with altered expression in schizophrenia, our previous work on human frontal cerebral cortex found the mRNA of Nogo, a myelin-associated protein which inhibits the outgrowth of neurites and nerve terminals, to be overexpressed in schizophrenia. Because those earlier results did not examine tissues for the separate Nogo A, B and C isoforms from age- and sex-matched individuals, we repeated the study for all three isoforms, using a new set of tissues from matched individuals, and using the more accurate method of quantitative real-time PCR (polymerase chain reaction). We found Nogo C to be overexpressed by 26% in the schizophrenia tissues, which is in accordance with our earlier results. The expression of Nogo B was statistically significantly reduced by 17% in the frontal cortices from individuals who had been diagnosed as having had severe depression. Furthermore, we show that there is a direct correlation between the expression of Nogo A and C and the presence of alleles with a CAA insert, irrespective of disease status. While upregulation of Nogo C expression may play a role in schizophrenia, altered Nogo B may contribute to the clinical condition of depression. Nogo A showed a statistically non-significant increase in expression in schizophrenia.
• 2.56

  Impact points

  Increased expression of calcium/calmodulin-dependent protein kinase IIbeta in frontal cortex in schizophrenia and depression.

  G Novak, P Seeman, T Tallerico

  Synapse (New York, N.Y.). 02/2006; 59(1):61-8.

  In searching for genes dysregulated in schizophrenia, we measured the expression of the two splice variants of calcium/calmodulin-dependent protein kinase II (CaMKIIalpha and CaMKIIbeta) in postmortem frontal cerebral cortex tissues from patients who had died with schizophrenia, bipolar disorder, or... [more] In searching for genes dysregulated in schizophrenia, we measured the expression of the two splice variants of calcium/calmodulin-dependent protein kinase II (CaMKIIalpha and CaMKIIbeta) in postmortem frontal cerebral cortex tissues from patients who had died with schizophrenia, bipolar disorder, or severe depression. The mRNA levels of expression of these two splice variants were measured by real-time Quantitative PCR, using an Mx4000 instrument. The values for the expression of CaMKIIalpha and CaMKIIbeta were normalized by the expression of beta-glucuronidase in the tissues. The expression of CaMKIIalpha was significantly elevated in the depression tissues by 29%. The expression of CaMKIIbeta was significantly elevated in the schizophrenia tissues by 27%, and in the depression tissues by 36%. Because CaMKIIbeta influences the expression of many neuroreceptors and influences neural outgrowth and pruning, its altered expression in the cerebral cortex in schizophrenia or depression may contribute to these diseases.
• 2.00

  Impact points

  Schizophrenia and Nogo: elevated mRNA in cortex, and high prevalence of a homozygous CAA insert.

  G Novak, D Kim, P Seeman, T Tallerico

  Brain research. Molecular brain research. 12/2002; 107(2):183-9.

  Schizophrenia is a major psychiatric disorder which is hypothesized to result from abnormal neurodevelopment or neural changes in adulthood and possibly associated with altered gene expression. To search for genes overexpressed in schizophrenia, cDNA library subtractive hybridization experiments bet... [more] Schizophrenia is a major psychiatric disorder which is hypothesized to result from abnormal neurodevelopment or neural changes in adulthood and possibly associated with altered gene expression. To search for genes overexpressed in schizophrenia, cDNA library subtractive hybridization experiments between post-mortem human frontal cerebral cortices from schizophrenia individuals and neurological controls were carried out. One of the genes over-expressed in schizophrenia was identified as Nogo (also known as reticulon 4, RTN4, NI 250, or RTN-X), a myelin-associated protein which inhibits the outgrowth of neurites and nerve terminals. The elevated expression of Nogo mRNA in schizophrenia was confirmed by quantitative reverse transcription-polymerase chain reaction studies: 16.5 pg Nogo cDNA/microg total RNA in schizophrenia, and 10.2 pg Nogo cDNA/microg total RNA in controls (n=7; P=0.01, t-test for n<30). To identify possible polymorphisms in this gene, the Nogo nucleotide sequence was determined in a series of schizophrenia and control samples. The Nogo mRNA was found to contain a CAA insert polymorphism in the 3'-untranslated region. The prevalence of individuals homozygous for this CAA insert was significantly higher in schizophrenia compared to controls in genomic DNA samples extracted from post-mortem brain and blood samples: 17/81 or 21% in schizophrenia and 2/61 or 3% in controls (P=0.0022, chi(2)- and Fisher's exact-tests). Because the 3'-untranslated regions of eukaryotic genes are known to regulate gene expression, the increased frequency of the Nogo CAA insert in schizophrenia may contribute to abnormal regulation of Nogo gene expression, and may indicate a role for Nogo in disturbed neurodevelopment in schizophrenia.
• 2.00

  Impact points

  Schizophrenia: elevated mRNA for dopamine D2(Longer) receptors in frontal cortex.

  T Tallerico, G Novak, I S Liu, C Ulpian, P Seeman

  Brain research. Molecular brain research. 04/2001; 87(2):160-5.

  Because dopamine D2 receptors are the primary targets for antipsychotic drugs, including clozapine and quetiapine, and because some studies have found D2 receptors to be elevated in schizophrenia, we examined the mRNA of three forms of the D2 receptor, particularly the new form of the dopamine D2 re... [more] Because dopamine D2 receptors are the primary targets for antipsychotic drugs, including clozapine and quetiapine, and because some studies have found D2 receptors to be elevated in schizophrenia, we examined the mRNA of three forms of the D2 receptor, particularly the new form of the dopamine D2 receptor, D2(Longer), in post-mortem brains from patients who died with schizophrenia. Using quantitative competitive RT-PCR (reverse transcriptase-polymerase chain reaction), the D2(Longer) mRNA was higher in the frontal cortex, compared to control tissues. The mRNA concentration of D2(Long) and D2(Short) was also higher in the frontal cortex, compared to control tissues. Although most of the schizophrenia patients had received different antipsychotic drugs for varying periods of time, the mRNA of D2(Longer), as well as that for D2(Long) and D2(Short), in such medicated tissues was similar to that in a frontal cortex tissue from a patient who had reliably never received antipsychotic drugs. It is possible, therefore, that the elevation of the mRNAs for D2(Longer), D2(Long) and D2(Short) in the frontal cortex may be related to the disease of schizophrenia itself.
• 2.00

  Impact points

  Schizophrenia: elevated mRNA for calcium-calmodulin-dependent protein kinase IIbeta in frontal cortex.

  G Novak, P Seeman, T Tallerico

  Brain research. Molecular brain research. 11/2000; 82(1-2):95-100.

  Because amphetamine releases two to three times more dopamine in schizophrenia patients than in control subjects, and because calcium-calmodulin-dependent protein kinase II has a key role in the enhanced action of amphetamine-induced dopamine release in rats, the synaptic content of calcium-calmodul... [more] Because amphetamine releases two to three times more dopamine in schizophrenia patients than in control subjects, and because calcium-calmodulin-dependent protein kinase II has a key role in the enhanced action of amphetamine-induced dopamine release in rats, the synaptic content of calcium-calmodulin-dependent protein kinase IIbeta mRNA was measured (by quantitative competitive RT-PCR; reverse transcriptase-polymerase chain reaction) in seven frontal cerebral cortices of post-mortem brains from patients who had schizophrenia and in seven control tissues. The results indicate that the mRNA of this kinase is elevated in the schizophrenia frontal cortex.
• 4.05

  Impact points

  The role of brain computed tomography in evaluating children with new onset of seizures in the emergency department.

  J Maytal, J M Krauss, G Novak, J Nagelberg, M Patel

  Epilepsia. 09/2000; 41(8):950-4.

  BACKGROUND: The purpose of neuroimaging of a patient with new onset of seizures is to demonstrate cause and explore the prognosis. It was recently recommended that emergency brain computed tomography (CT) be performed only in adult seizure patients with an increased likelihood of life-threatening le... [more] BACKGROUND: The purpose of neuroimaging of a patient with new onset of seizures is to demonstrate cause and explore the prognosis. It was recently recommended that emergency brain computed tomography (CT) be performed only in adult seizure patients with an increased likelihood of life-threatening lesions, i.e., those with new focal deficits, persistent altered mental status, fever, recent trauma, persistent headaches, history of cancer, history of anticoagulation, or suspicion of acquired immunodeficiency syndrome. The objective of this study was to determine the diagnostic utility of emergency brain CT in children who present to the emergency department with new onset of seizures. METHODS: A 1-year retrospective chart review of all children who presented to the emergency department of the Schneider Children's Hospital with a new onset of seizures and who underwent CT of the brain, excluding children with simple febrile seizures. RESULTS: Sixty-six patients, 34 boys and 32 girls with a mean age of 4.9 years, qualified for inclusion in the study. Fifty-two patients (78.8%) had normal CT results and 14 patients (21.2%) had abnormal CT results. Seizure cause was considered cryptogenic in 33 patients, of whom 2 (6%) had abnormal CT results; neither patient required intervention. Seizure cause was considered symptomatic in 20 patients, of whom 12 (60%) had abnormal CT results (p < 0.0001). In two patients with abnormal CT scans (both acute symptomatic), the imaging findings were of immediate therapeutic significance and were predictable from the clinical history and the physical examination. None of the 13 patients with complex febrile seizure cause had an abnormal CT scan. Patients with partial convulsive seizures were more likely to have abnormal CT scans than patients with generalized convulsive seizures, but the difference was not statistically significant. CONCLUSIONS: The routine practice in many pediatric emergency departments of obtaining brain CT scans for all patients with new onset of nonfebrile seizures is unjustified. History and physical examination are sufficient to identify those patients for whom such studies are likely to be appropriate. Emergent CT is not indicated for patients with no known seizure risk factors, normal neurological examinations, no acute symptomatic cause other than fever, and reliable neurological follow-up. For these patients, referral to a pediatric neurologist for further workup, including electroencephalography and the more diagnostically valuable magnetic resonance imaging, would be more appropriate.
• 4.05

  Impact points

  The value of early postictal EEG in children with complex febrile seizures.

  J Maytal, R Steele, L Eviatar, G Novak

  Epilepsia. 03/2000; 41(2):219-21.

  PURPOSE: To assess the usefulness of an early postictal EEG in neurologically normal children with complex febrile seizures. METHODS: We conducted a retrospective chart review of all neurologically normal children who were hospitalized over a period of 2.5 years after complex febrile seizures, and h... [more] PURPOSE: To assess the usefulness of an early postictal EEG in neurologically normal children with complex febrile seizures. METHODS: We conducted a retrospective chart review of all neurologically normal children who were hospitalized over a period of 2.5 years after complex febrile seizures, and had an EEG up to 1 week after the seizure. RESULTS: Thirty-three patients (mean age, 17.8 months) qualified for inclusion into the study. Twenty-four patients were qualified as complex cases based on one factor (prolonged in 9, repetitive in 13, and focal in 2). Nine other patients had two complex factors: in six patients, the seizures were long and repetitive; in two patients, the seizures were focal and repetitive; and in one patient, the seizures were long, focal, and repetitive. Thirteen (39%) patients experienced prior febrile seizures. All 33 patients had a normal postictal sleep EEG. Our results indicate with a 95% probability that the true rate of abnormalities in an early postictal EEG performed on otherwise normal children with complex febrile seizures is 8.6% or less. CONCLUSIONS: The yield of abnormalities of an early postictal EEG in this population is low and similar to the reported rate of abnormalities in children with simple febrile seizures. The routine practice of obtaining an early EEG in neurologically normal children with complex febrile seizures is not justified.
• 8.93

  Impact points

  Effects of clozapine on auditory event-related potentials in schizophrenia.

  D Umbricht, D Javitt, G Novak, J Bates, S Pollack, J Lieberman, J Kane

  Biological psychiatry. 11/1998; 44(8):716-25.

  BACKGROUND: Schizophrenia is associated with cognitive deficits that are an intrinsic component of the disorder. Clozapine is an atypical antipsychotic that is superior to typical agents in the treatment of positive symptoms. The degree to which clozapine ameliorates cognitive deficits, however, is ... [more] BACKGROUND: Schizophrenia is associated with cognitive deficits that are an intrinsic component of the disorder. Clozapine is an atypical antipsychotic that is superior to typical agents in the treatment of positive symptoms. The degree to which clozapine ameliorates cognitive deficits, however, is still controversial. Mismatch negativity (MMN), N200 (N2), and P300 (P3) are cognitive event-related potentials (ERPs) that index preattentive (MMN) and attention-dependent information processing (N2, P3) and provide a measure of cognitive deficits associated with schizophrenia. In schizophrenic patients deficient generation of MMN, N2, and P3 has been observed, suggesting impairments of discrete stages of information processing. METHODS: This study investigates the effects of clozapine treatment on MMN, N2, and P3 generation. Patients were recruited from a haloperidol-controlled, double-blind treatment study of clozapine in chronic schizophrenia. ERPs were obtained at the beginning of the study and after 9 weeks (4 patients) and 16 weeks (13 patients) of treatment. RESULTS: Clozapine treatment was associated with a significant increase of P3 amplitude, which was not observed in the haloperidol group; however, clozapine treatment did not affect deficits in MMN and N2. CONCLUSIONS: These findings suggest that clozapine--in contrast to conventional antipsychotics--improves electrophysiological measures of attention-dependent information processing, but does not ameliorate preattentive deficits.
• 8.17

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  Risk factors for status epilepticus in children with symptomatic epilepsy.

  G Novak, J Maytal, A Alshansky, C Ascher

  Neurology. 09/1997; 49(2):533-7.

  The purpose of this study was to determine risk factors for status epilepticus (SE) in children with symptomatic epilepsy through a retrospective case-control study. Patients (44 children with a prior diagnosis of symptomatic epilepsy experiencing one or more episodes of SE between January 1, 1991, ... [more] The purpose of this study was to determine risk factors for status epilepticus (SE) in children with symptomatic epilepsy through a retrospective case-control study. Patients (44 children with a prior diagnosis of symptomatic epilepsy experiencing one or more episodes of SE between January 1, 1991, and June 1, 1995) were matched for age at follow-up to controls (88 children with symptomatic epilepsy without SE during that interval) and medical records were reviewed. Patients and controls did not differ in etiology or in age at epilepsy onset (1 year 5 months [SD, 2 years 3 months] versus 1 year 3 months [SD, 1 year 5 months]). Univariate analysis revealed significant associations between SE and several factors, including history of a first seizure as SE, partial epilepsy, partial seizures with secondary generalization, focal paroxysmal abnormalities and focal background abnormalities on EEG, and generalized abnormalities on neuroimaging. Groups did not differ in the proportion of patients on polypharmacy or with subtherapeutic serum antiepileptic drug levels, but there was a trend for greater use of phenobarbital in patients (57% versus 38%, odds ratio (OR) = 2.6, p = 0.057). With multiple logistic regression, four factors emerged as independent predictors of SE risk: focal background EEG abnormalities (OR = 6.51, p = 0.0005), partial seizures with secondary generalization (OR = 4.61, p = 0.0021), first seizure as SE (OR = 3.99, p = 0.034), and generalized abnormalities on neuroimaging (OR = 2.85, p = 0.034). These four factors are indicators of a higher risk of SE in children with symptomatic epilepsy.