Publications by authors named "André Palmini"

77 Publications

The COVID-19 outbreak and PNES: The impact of a ubiquitously felt stressor.

Epilepsy Behav 2021 04 12;117:107852. Epub 2021 Feb 12.

Department of Clinical Neuroscience, School of Medicine, Pontificia University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Service of Neurology, Hospital São Lucas, Pontificia University of Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.

Objective: We aimed to assess frequency of functional seizures or psychogenic nonepileptic seizures (PNES) during the COVID-19 outbreak and to recognize possible factors associated with worsening in this population.

Methods: In this cross-sectional study conducted during the second phase of the pandemic, adult patients with PNES documented by video-EEG and followed up in two tertiary epilepsy centers responded to a structured telephone survey. Data were gathered on demographics, clinical features and frequency of PNES, history of psychiatric comorbidity, access to treatment, as well as on anxiety (GAD-7 items) and depressive symptoms (NDDI-E).

Results: Fifty-four patients (78% female; mean age of 31.36 years [SD = 10.6]) were contacted and 15 (28%) reported increased frequency of PNES during the pandemic. Higher scores of GAD-7 items (p < 0.001) and NDDI-E (p < 0.001) were associated with PNES worsening. There was strong evidence of a correlation between higher stress levels (p < 0.001) and poor sleep quality (p 0.005) with PNES aggravation. After regression, stress was the strongest predictor of PNES increased frequency.

Significance: Patients with functional neurological disorders are vulnerable during ubiquitously felt stressors. However, the atmosphere of uncertainty did not affect these patients equally. Patients with PNES showing symptoms of anxiety and depression are at higher risk of seizure worsening. Early identification of this subset of patients may prevent this detrimental outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2021.107852DOI Listing
April 2021

Control of drop attacks with selective posterior callosotomy: Anatomical and prognostic data.

Epilepsy Res 2021 Mar 5;171:106544. Epub 2021 Jan 5.

Porto Alegre Epilepsy Surgery Program, Neurology and Neurosurgery Services, Hospital São Lucas, Brazil; School of Medicine, Pontificia Universidade Catolica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. Electronic address:

Objective: In a previous proof of concept study, selective posterior callosotomy achieved similar degree of control of drop attacks as total callosotomy, while sparing prefrontal interconnectivity. The present study aims to confirm this finding in a larger cohort and to provide anatomical and prognostic data.

Methods: Fifty-one patients with refractory drop attacks had selective posterior callosotomy and prospective follow up for a mean of 6.4 years. Twenty-seven patients had post-operative magnetic resonance imaging (MRI) and 18 had tractography (DTI) of remaining callosal fibers. Pre and postoperative falls were quantified and correlated with demographic, clinical and imaging data.

Results: Mean monthly frequency of drop attacks had a 95 % reduction, from 297 before to 16 after the procedure. Forty- one patients (80 %) had either complete or greater than 90 % control of the epileptic falls. Age and duration of epilepsy at surgery correlated with outcome (p values, respectively, 0.042 and 0.005). Mean index of callosal section along the posterior-to-anterior axis was 53.5 %. Extending the posterior section anterior to the midbody of the corpus callosum did not correlate with seizure control (p 0.91), providing fibers interconnecting the primary motor (M1) and caudal supplementary motor areas (SMA) were sectioned. Only one patient had a notable surgical complication which resolved in two days.

Conclusions: This level III cohort study with objective outcome assessment confirms that selective posterior callosotomy is safe and effective to control epileptic falls. Younger patients with smaller duration of epilepsy have better results. A posterior section contemplating the splenium, isthmus and posterior half of the body (posterior midbody) seems sufficient to achieve complete or almost complete control of drop attacks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eplepsyres.2020.106544DOI Listing
March 2021

Drebrin expression patterns in patients with refractory temporal lobe epilepsy and hippocampal sclerosis.

Epilepsia 2020 08 14;61(8):1581-1594. Epub 2020 Jul 14.

Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.

Objective: Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan-drebrin) isoforms, respectively.

Methods: Hippocampal sections from drug-resistant TLE patients with hippocampal sclerosis (HS; TLE, n = 33), of whom 31 presented with type 1 HS and two with type 2 HS, and autopsy control cases (n = 20) were assayed by immunohistochemistry and evaluated for neuron density, and drebrin A and pan-drebrin expression. Double-labeling immunofluorescences were performed to localize drebrin A-positive spines in dendrites (MAP2), and to evaluate whether drebrin colocalizes with inhibitory (GAD65) and excitatory (VGlut1) presynaptic markers.

Results: Compared to controls, TLE patients had increased pan-drebrin in all hippocampal subfields and increased drebrin A-immunopositive area in all hippocampal subfields but CA1. Drebrin-positive spine density followed the same pattern as total drebrin quantification. Confocal microscopy indicated juxtaposition of drebrin-positive spines with VGlut1-positive puncta, but not with GAD65-positive puncta. Drebrin expression in the dentate gyrus of TLE cases was associated negatively with seizure frequency and positively with verbal memory. TLE patients with lower drebrin-immunopositive area in inner molecular layer (IML) than in outer molecular layer (OML) had a lower seizure frequency than those with higher or comparable drebrin-immunopositive area in IML compared with OML.

Significance: Our results suggest that changes in drebrin-positive spines and drebrin expression in the dentate gyrus of TLE patients are associated with lower seizure frequency, more preserved verbal memory, and a better postsurgical outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.16595DOI Listing
August 2020

Selective Posterior Callosotomy for Treatment of Epileptic Drop Attacks: Video Documentation of the Surgical Technique: 2-Dimensional Operative Video.

Oper Neurosurg (Hagerstown) 2020 Oct;19(5):E514-E515

Epilepsy Surgery Program, Department of Neurosurgery and Neurology , Hospital São Lucas, Porto Alegre, RS, Brazil.

This is a surgical technique video of selective posterior callosotomy (SPC), a novel surgical procedure to alleviate refractory epileptic drop attacks.1 Departing from traditional approaches aiming the anterior half or the entire callosum, SPC sections the posterior half of the callosum sparing prefrontal connectivity.1 Drop attacks are generalized epileptic seizures characterized by sudden falls.1 These seizures are often seen in diffuse brain pathology associated with generalized or multifocal epilepsies, whose electroencephalogram (EEG) "fingerprint" is bilaterally synchronous epileptic discharges.1 Sectioning the callosum to control drop attacks follows the rationale that the rapid synchronization of discharges between motor and premotor regions of both hemispheres is the basis.1 The standard approach to callosotomies always contemplated the anterior fibers of the callosum.2 Literature reports that anterior sections lead to unsatisfactory control of drop attacks, and results are improved when extended into a total callosotomy.2,3 This evidence coupled with diffusion tensor imaging (DTI) findings showing that motor and premotor fibers actually cross through posterior half of the callosum led us to hypothesize that selective section of the posterior half of the callosum would section all relevant motor fibers and control drop attacks to a similar extent to total callosotomies, with the advantage of sparing prefrontal interconnectivity3 and no split-brain syndrome. Both our series, one retrospective, followed by a new prospective study have confirmed SPC to be a safe procedure, leading to complete or greater than 90% control of epileptic falls in 85% of patients.1 The video presented here was recorded during a selective posterior callosotomy performed on a 13-yr-old girl who had hundreds of uncontrollable drop attacks per day. Falls were completely controlled with significant gains in psychomotor development and cognition, after 5 yr of follow-up. The patient provided signed consent to the surgical procedure, video acquisition, photo acquisition, and storage at operations, and the publication of this material.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ons/opaa137DOI Listing
October 2020

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Seizure 2020 May 5;78:31-37. Epub 2020 Mar 5.

Neurocenter Bellevue, Zurich, Switzerland.

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2020.02.018DOI Listing
May 2020

Analysis of genes involved in cell proliferation, adhesion, and control of apoptosis during embryonic neurogenesis in Induced Pluripotent Stem Cells (iPSCs) from patients with Focal Cortical Dysplasia.

Brain Res Bull 2020 02 6;155:112-118. Epub 2019 Dec 6.

Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil; Graduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil; Graduate Program in Medicine, Pediatrics and Child Health, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil; School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil. Electronic address:

Focal cortical dysplasia (FCD) is a malformation of cortical development which is strongly associated with drug-refractory epilepsy. Certain studies have demonstrated an increase in mTOR signaling in patients with FCD on the basis of observation of phosphorylated molecules. The aim of the present study was to verify the differences in genes involved in cell proliferation, adhesion, and control of apoptosis during embryonic neurogenesis in iPSCs derived from the Focal Cortical Dysplasia. Fibroblasts were obtained from the skin biopsies of patients with FCD (n = 2) and controls (n = 2). iPSCs were generated by exposing the fibroblasts to viral vectors that contained the Yamanaka factors (OCT4, SOX2, KLF4, and c-MYC genes) responsible for promoving cell reprogramation. The fibroblasts and iPSCs were tested during different phases of neurodifferentiation for migration capacity and expression of the genes involved in the PI3K pathway. Fibroblasts of patients with FCD migrated with greater intensity during the first two time points of analyses. iPSCs did not exhibit any difference in cell migration between the groups. Fibroblasts, brain tissue, and iPSCs of the patients with FCD exhibited a significant reduction in the relative expression values of 4EBP-1. During neurodevelopment, the iPSCs from patients with FCD exhibited a reduction in the expression of cIAP-1, cIAP-2, PI3K, β-Catenin and 4EBP-1 gene. We suggest that the differences observed in the migration potential of adult cells and in the gene expression related to the fundamental processes involved in normal brain development during the neurodifferentiation process might be associated with cortical alteration in the patients with FCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainresbull.2019.11.016DOI Listing
February 2020

Critique of the 2017 epileptic seizure and epilepsy classifications.

Epilepsia 2019 06 28;60(6):1032-1039. Epub 2019 Mar 28.

Department of Neurology, University Hospitals Cleveland Medical Center, Cleveland, Ohio.

This article critiques the International League Against Epilepsy (ILAE) 2015-2017 classifications of epilepsy, epileptic seizures, and status epilepticus. It points out the following shortcomings of the ILAE classifications: (1) they mix semiological terms with epileptogenic zone terminology; (2) simple and widely accepted terminology has been replaced by complex terminology containing less information; (3) seizure evolution cannot be described in any detail; (4) in the four-level epilepsy classification, level two (epilepsy category) overlaps almost 100% with diagnostic level one (seizure type); and (5) the design of different classifications with distinct frameworks for newborns, adults, and patients in status epilepticus is confusing. The authors stress the importance of validating the new ILAE classifications and feel that the decision of Epilepsia to accept only manuscripts that use the ILAE classifications is premature and regrettable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.14699DOI Listing
June 2019

Migration and Synaptic Aspects of Neurons Derived from Human Induced Pluripotent Stem Cells from Patients with Focal Cortical Dysplasia II.

Neuroscience 2019 06 19;408:81-90. Epub 2019 Mar 19.

Brain Institute of Rio Grande do Sul (BraIns), Medical School, Av. Ipiranga, 6690 - Building 63, 90610-000 Porto Alegre, RS, Brazil. Electronic address:

Malformations of cortical development (MCDs) include many different Central Nervous System (CNS) disorders related to a complex process of cortex formation. In children with refractory epilepsy to drug treatment undergoing surgery, focal cortical dysplasia (FCD), one of the MCDs, is considered the most common structural brain lesion found. This study aimed to study the possible alterations in neural differentiation process of human induced pluripotent stem cells (hiPSCs) related to migration and synaptic aspects from fibroblasts of two individuals affected by FCD type IIb (45-year-old male and 12-year-old female) and normal individuals. At the days 14th, 22nd and 35th, hiPSCs were neural differentiated and analyzed. Using qRT-PCR approach, the expression of 9 genes associated with synaptic and neural migration were quantified. Diagnostic of both patients was consistent with FCD type IIb. Our results showed that in all processes and groups, individuals with dysplasia presented alterations in most part of the genes in relation to control individuals. According to our results, it is suggested that the different expressions are mainly involved in alterations of the expression of receptors and capture sites, timing, coupling of synaptic vesicles with the presynaptic membrane, regulation of ion channel and synaptic exocytosis, imbalance of the apoptosis process and abnormal microtubules that may also contribute to delays in synaptogenesis. Thus, brain formation with dysplasia is probably influenced by these genes studied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2019.03.025DOI Listing
June 2019

Classification of paroxysmal events and the four-dimensional epilepsy classification system.

Epileptic Disord 2019 02;21(1):1-29

Case Medical Center - Pediatrics, Cleveland, Ohio, USA.

This educational review describes the classification of paroxysmal events and a four-dimensional epilepsy classification system. Paroxysmal events are classified as epileptic and non-epileptic paroxysmal events. Non-epileptic events are, in turn, classified as psychogenic and organic paroxysmal events. The following four dimensions are used to classify epileptic paroxysmal events: ictal semiology, the epileptogenic zone, etiology, and comorbidities. Efforts are made to keep these four dimensions as independent as possible. The review also includes 12 educational vignettes and three more detailed case reports classified using the 2017 classification of the ILAE and the four-dimensional epilepsy classification. In addition, a case is described which is classified using the four-dimensional epilepsy classification with different degrees of precision by an emergency department physician, a neurologist, and an epileptologist. [Published with video sequences on www.epilepticdisorders.com].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2019.1033DOI Listing
February 2019

Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer's Dementia.

Mol Neurobiol 2019 Jul 9;56(7):4916-4924. Epub 2018 Nov 9.

Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging (MCSA), Douglas Mental Health Research Institute, 6825, boul. LaSalle Blvd., Montréal, QC, H4H1R3, Canada.

We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer's disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [F]FDG and [F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses. Using voxel-based interaction models at voxel level, we tested whether the regional hypometabolism is associated with FA in the angular bundle and regional amyloid-β deposition. In the AD patients, [F]FDG hypometabolism in the striatum, mesiobasal temporal, orbitofrontal, precuneus, and cingulate cortices were associated with the interaction between high levels of [F]Florbetapir standard uptake value ratios (SUVR) in these regions and low FA in the angular bundle. We found that the interaction between, rather than the independent effects of, high levels of amyloid-β deposition and WM integrity disruption determined limbic hypometabolism in patients with AD. This finding highlights a more integrative model for AD, where the interaction between partially independent processes determines the glucose hypometabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-018-1405-1DOI Listing
July 2019

Neuropsychiatric features of the coexistence of epilepsy and psychogenic nonepileptic seizures.

J Psychosom Res 2018 08 26;111:83-88. Epub 2018 May 26.

Post-Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil; Department of Neurology, Faculty of Medicine, PUCRS, Brazil; Service of Neurology, Hospital São Lucas, PUCRS, Brazil; Service of Neurosurgery, Hospital São Lucas, PUCRS, Brazil.

Objective: To investigate demographic, epidemiologic and psychiatric features suggestive of the coexistence epilepsy (ES) and psychogenic nonepileptic seizures (PNES) that may contribute to precocious suspicion of the association.

Methods: In this exploratory study, all patients older than 16 years admitted to prolonged video-electroencephalogram monitoring were evaluated about demographic, epileptological and psychiatric features. Detailed psychiatric assessment using M.I.N.I.-plus 5.0, Beck Anxiety Inventory, Beck Depression Inventory and the Childhood Trauma Questionnaire (CTQ) was performed. Data were collected previous to the final diagnosis and patients with ES-only, PNES-only or coexistence of ES/PNES were compared.

Results: Of 122 patients admitted to epilepsy monitoring unit, 86 patients were included and 25 (29%) had PNES. Twelve (14%) had PNES-only, 13 (15%) had ES/PNES and the remaining 61 (71%) had only ES. A coexistence of ES and PNES was associated with clinical report of more than one seizure type (p˂0.001), nonspecific white matter hyperintensities on MRI (p < .001) and a past of psychotic disorder (p = .005). In addition, these patients had significantly more emotional abuse and neglect (p < .002 and 0.001, respectively). Somatization (including conversion disorder) was the most common diagnosis in patients with PNES- only (83%) and co-existing of PNES and ES (69.2%), differentiating both from ES-only patients (p < .001).

Conclusion: The high prevalence of this coexistence ES/PNES in this study reinforces a need to properly investigate PNES, especially in patients with confirmed ES who become refractory to medical treatment with antiepileptic drugs. The neuropsychiatric assessment may help to diagnostic suspicion and in the planning of therapeutic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychores.2018.05.014DOI Listing
August 2018

What is in a name? A closer look at callosotomies.

Dev Med Child Neurol 2018 03;60(3):323

Neurology and Neurosurgery Services and Porto Alegre Epilepsy Surgery Program, Hospital São Lucas da Pontificia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dmcn.13641DOI Listing
March 2018

What is in a name? A closer look at callosotomies.

Dev Med Child Neurol 2018 03;60(3):323

Neurology and Neurosurgery Services and Porto Alegre Epilepsy Surgery Program, Hospital São Lucas da Pontificia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/dmcn.13641DOI Listing
March 2018

Association between switching antiepileptic drug products and healthcare utilization: A systematic review.

Epilepsy Behav 2017 08 20;73:166-172. Epub 2017 Jun 20.

Faculty of Medicine, Neurology Service & Porto Alegre Epilepsy Surgery Program, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. Electronic address:

Aims: There is ongoing concern whether switching between different antiepileptic drug (AED) products may compromise patient care. We systematically reviewed changes in healthcare utilization following AED switch.

Methods: We searched MEDLINE and EMBASE databases (1980-October 2016) for studies that assessed the effect of AED switching in patients with epilepsy on outpatient visits, emergency room visits, hospitalization and hospital stay duration.

Results: A total of 14 articles met the inclusion criteria. All were retrospective studies. Four provided findings for specific AEDs only (lamotrigine, topiramate, phenytoin and divalproex), 9 presented pooled findings from multiple AEDs, and 1 study provided both specific (lamotrigine, topiramate, oxcarbazepine, and levetiracetam) and pooled findings. Three studies found an association between a switch of topiramate and an increase in healthcare utilization. Another three studies found that a brand-to-generic lamotrigine switch was not associated with an increased risk of emergently treated events (ambulance use, ER visits or hospitalization). The outcomes of the pooled AED switch studies were inconsistent; 5 studies reported an increased healthcare utilization while 5 studies did not.

Conclusion: Studies that have examined the association between an AED switch and a change in healthcare utilization report conflicting findings. Factors that may explain these inconsistent outcomes include inter-study differences in the type of analysis undertaken (pooled vs individual AED data), the covariates used for data adjustment, and the type of switch examined. Future medical claim database studies employing a prospective design are encouraged to address these and other factors in order to enhance inter-study comparability and extrapolation of findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2017.05.010DOI Listing
August 2017

Induced pluripotent stem cells from patients with focal cortical dysplasia and refractory epilepsy.

Mol Med Rep 2017 Apr 1;15(4):2049-2056. Epub 2017 Mar 1.

Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS 90610000, Brazil.

Focal cortical dysplasia (FCD) is caused by numerous alterations, which can be divided into abnormalities of the cortical architecture and cytological variations; however, the exact etiology of FCD remains unknown. The generation of induced pluripotent stem cells (iPSCs) from the cells of patients with neurological diseases, and their subsequent tissue‑specific differentiation, serves as an invaluable source for testing and studying the initial development and subsequent progression of diseases associated with the central nervous system. A total of 2 patients demonstrating seizures refractory to drug treatment, characterized as FCD Type IIb, were enrolled in the present study. Fibroblasts were isolated from residual skin fragments obtained from surgical treatment and from brain samples obtained during surgical resection. iPSCs were generated following exposure of fibroblasts to viral vectors containing POU class 5 homeobox 1 (OCT4), sex determining region Y‑box 2 (SOX2), Kruppel‑like factor 4 and c‑MYC genes, and were characterized by immunohistochemical staining for the pluripotent markers homeobox protein NANOG, SOX2, OCT4, TRA1‑60 and TRA1‑81. The brain samples were tested with antibodies against protein kinase B (AKT), phosphorylated‑AKT, mechanistic target of rapamycin (mTOR) and phosphorylated‑mTOR. Analysis of the AKT/mTOR pathway revealed a statistically significant difference between the cerebral tissues of the two patients, which were of different ages (45 and 12 years old). Clones with the morphological features of embryonic cells were detected on the 13th day and were characterized following three subcultures. The positive staining characteristics of the embryonic cells confirmed the successful generation of iPSCs derived from the patients' fibroblasts. Therefore, the present study presents a method to obtain a useful cellular source that may help to understand embryonic brain development associated with FCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2017.6264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364982PMC
April 2017

The approach to patients with psychogenic nonepileptic seizures in epilepsy surgery centers regarding diagnosis, treatment, and education.

Epilepsy Behav 2017 03 26;68:78-83. Epub 2017 Jan 26.

Department of Psychiatry, Rhode Island Hospital, Brown University, Providence, RI, USA; Department of Neurology, Rhode Island Hospital, Brown University, Providence, RI, USA.

Previous studies, using surveys, provided an understanding about how health-care providers address patients with PNES. To date, there is limited information on the management of patients with PNES by tertiary referral centers for epilepsy. In this study, we surveyed 11 Brazilian epilepsy center directors about diagnosis, treatment, education and research on PNES. Respondents reported that patients with PNES represented 10-20% of all adult patients recorded by video-EEG (VEEG). All respondents recognized VEEG as the method to confirm the diagnosis, and 81.8% used this approach for confirmation. Most centers had a standard protocol for diagnosis. None of the centers had a particular protocol to treat PNES, but 90.9% had a uniform treatment approach including therapy and educational measures. Psychotherapy was not easily obtained in nine centers (81.8%). Seven (63.3%) centers reported ongoing research projects with PNES. Five centers referred to an educational PNES program discussing diagnosis, but only one reported an educational program for treatment. This study showed a commitment to PNES diagnosis; however, some gaps remain regarding treatment and training, namely implementing a psychotherapy approach for patients and providing educational curricula for clinicians.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2016.12.013DOI Listing
March 2017

Selective posterior callosotomy for drop attacks: A new approach sparing prefrontal connectivity.

Neurology 2016 Nov 12;87(19):1968-1974. Epub 2016 Oct 12.

From the Porto Alegre Epilepsy Surgery Program, Neurology and Neurosurgery Services, Hospital São Lucas (E.P., W.A.M., N.A., M.P., T.M.F., J.C.d.C., M.H., A.P.), The Brain Institute (M.P., R.B.S., J.C.d.C.), and Faculty of Medicine (E.P., N.A., M.P., L.P., R.S., C.S., J.R.H., R.B.S., J.C.d.C., M.H., A.P.), Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil; and Department of Neurosurgery (T.T.), Universitaire Ziekenhuizen Leuven, Belgium.

Objective: To evaluate a novel approach to control epileptic drop attacks through a selective posterior callosotomy, sparing all prefrontal interconnectivity.

Methods: Thirty-six patients with refractory drop attacks had selective posterior callosotomy and prospective follow-up for >4 years. Falls, episodes of aggressive behavior, and IQ were quantified. Autonomy in activities of daily living, axial tonus, and speech generated a functional score ranging from 0 to 13. Subjective effect on patient well-being and caregiver burden was also assessed.

Results: Median monthly frequency of drop attacks decreased from 150 to 0.5. Thirty patients (83%) achieved either complete or >90% control of the falls. Need for constant supervision decreased from 90% to 36% of patients. All had estimated IQ below 85. Median functional score increased from 7 to 10 (p = 0.03). No patient had decrease in speech fluency or hemiparesis. Caregivers rated the effect of the procedure as excellent in 40% and as having greatly improved functioning in another 50%. Clinical, EEG, imaging, and cognitive variables did not correlate with outcome.

Conclusions: This cohort study with objective outcome assessment suggests that selective posterior callosotomy is safe and effective to control drop attacks, with functional and behavioral gains in patients with intellectual disability. Results are comparable to historical series of total callosotomy and suggest that anterior callosal fibers may be spared.

Classification Of Evidence: This study provides Class III evidence that selective posterior callosotomy reduces falls in patients with epileptic drop attacks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000003307DOI Listing
November 2016

Diagnostic utility of invasive EEG for epilepsy surgery: Indications, modalities, and techniques.

Epilepsia 2016 11 28;57(11):1735-1747. Epub 2016 Sep 28.

GIN INSERM U1216, Grenoble-Alpes Hospital and University, Grenoble, France.

Many patients with medically refractory epilepsy now undergo successful surgery based on noninvasive diagnostic information, but intracranial electroencephalography (IEEG) continues to be used as increasingly complex cases are considered surgical candidates. The indications for IEEG and the modalities employed vary across epilepsy surgical centers; each modality has its advantages and limitations. IEEG can be performed in the same intraoperative setting, that is, intraoperative electrocorticography, or through an independent implantation procedure with chronic extraoperative recordings; the latter are not only resource intensive but also carry risk. A lack of understanding of IEEG limitations predisposes to data misinterpretation that can lead to denying surgery when indicated or, worse yet, incorrect resection with adverse outcomes. Given the lack of class 1 or 2 evidence on IEEG, a consensus-based expert recommendation on the diagnostic utility of IEEG is presented, with emphasis on the application of various modalities in specific substrates or locations, taking into account their relative efficacy, safety, ease, and incremental cost-benefit. These recommendations aim to curtail outlying indications that risk the over- or underutilization of IEEG, while retaining substantial flexibility in keeping with most standard practices at epilepsy centers and addressing some of the needs of resource-poor regions around the world.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.13515DOI Listing
November 2016

Mother and daughter with adolescent-onset severe frontal lobe dysfunction and epilepsy.

Dement Neuropsychol 2016 Jul-Sep;10(3):238-243

Neurology Service, São Lucas Hospital, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre RS, Brazil.

Familial cases of early-onset prominent frontal lobe dysfunction associated with epilepsy have not been reported to date. We report a mother and her only daughter with incapacitating behavioral manifestations of frontal lobe dysfunction and epilepsy of variable severity. The possibility of a hitherto undescribed genetic condition is discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/S1980-5764-2016DN1003011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642421PMC
December 2017

Imaging Alzheimer's disease pathophysiology with PET.

Dement Neuropsychol 2016 Apr-Jun;10(2):79-90

Translational Neuroimaging Laboratory (TNL), McGill Center for Studies in Aging (MCSA), Douglas Mental Health Research Institute, Montreal, Canada.

Alzheimer's disease (AD) has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI), and dementia stages. Positron emission tomography (PET) associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/S1980-5764-2016DN1002003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642398PMC
December 2017

Variables associated with co-existing epileptic and psychogenic nonepileptic seizures: a systematic review.

Seizure 2016 Apr 2;37:35-40. Epub 2016 Mar 2.

Medicine and Health Sciences Post-Graduate Program, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Neurology, Hospital São Lucas, PUCRS, Brazil; Porto Alegre Epilepsy Surgery Program Service, Hospital São Lucas, PUCRS, Brazil; Internal Medicine Department, Medical School, PUCRS, Brazil. Electronic address:

Purpose: Epileptic seizures (ES) have many mimickers, perhaps the most relevant being psychogenic nonepileptic seizures (PNES). The picture is even more challenging when PNES are associated with ES in a given patient. The aim of this research paper was to delineate the demographic, epileptological and psychiatric profile of that specific population.

Methods: A systematic review was carried out from 2000 to 2015 for articles in English, French, Italian, Spanish and Portuguese in PUBMED and EMBASE. Cohort or case-control studies reporting prospective or retrospective original data comparing patients with co-existing ES and PNES with those who had PNES only and ES only have been included. In retained studies, the presence of PNES was confirmed by video-electroencephalography (V-EEG). Forty-eight abstracts were identified.

Results: Nine studies were retained. Most showed that female gender predominated in both groups with PNES. Patients with co-existing ES and PNES take higher number of antiepileptic drugs (AEDs) than PNES alone. Two studies showed association of concomitant ES and PNES with earlier age of seizure onset. Localizing EEG features and ES type were evaluated in only two studies and their association with either group was inconclusive. Somatoform, conversion or cluster B personality disorders were more frequent in subjects with PNES than with ES.

Discussion: Patients with concomitant ES and PNES are highly heterogeneous, challenging differentiation on clinical grounds. A diagnosis of conversion or somatoform, anxiety disorders, and the use of a higher number of AEDs than psychiatric medications may have an association with co-existing ES and PNES. Further studies are warranted to differentiate patients who only have PNES from those with co-existing ES and PNES.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2016.02.003DOI Listing
April 2016

Epilepsia partialis continua triggered by traumatic hand injury: a peripheral tuning of brain excitability?

Epileptic Disord 2016 Mar;18(1):13-8

Porto Alegre Epilepsy Surgery Program, Hospital São Lucas, Service of Neurology, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Internal Medicine, Division of Neurology, Faculty of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.

Epilepsia partialis continua is often refractory to antiepileptic medication and its causal relation to peripheral sensory stimuli has only rarely been suggested. We report a man who received surgery for temporal lobe epilepsy 10 years ago, who presented "de novo" epilepsia partialis continua following mild traumatic injury of the left hand. Continuous myoclonus of the left upper limb started the day after injury and persisted unabated for several weeks. Non-invasive evaluation was inconclusive. Acute electrocorticography during surgery under local anaesthesia revealed continuous, rhythmic spiking over the right sensorimotor cortex. Tailored excision of the posterior bank of the motor and adjacent sensory cortex immediately stopped the continuous myoclonus. Histopathology showed abnormal radial lamination and was compatible with focal cortical dysplasia type IA. Epilepsia partialis continua did not recur for seven years. Afferent stimuli from peripheral injury can disinhibit hyperexcitable sensorimotor cortex leading to epilepsia partialis continua. [Published with video sequences online].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/epd.2016.0798DOI Listing
March 2016

Callosotopy: leg motor connections illustrated by fiber dissection.

Brain Struct Funct 2017 01 14;222(1):661-667. Epub 2015 Dec 14.

Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium.

Precise anatomical knowledge of the structure of the corpus callosum is important in split-brain research and during neurosurgical procedures sectioning the callosum. According to the classic literature, commissural fibers connecting the motor cortex are situated in the anterior part of the corpus callosum. On the other hand, more recent imaging studies using diffusion tensor imaging indicate a more posterior topography of callosal fibers connecting motor areas. Topographical knowledge is especially critical when performing disconnective callosotomies in epilepsy patients who experience sudden loss of leg motor control, so-called epileptic drop attacks. In the current study, we aim to precisely delineate the topography of the leg motor connections of the corpus callosum. Of 20 hemispheres obtained at autopsy, 16 were dissected according to Klingler's fiber dissection technique to study the course and topography of callosal fibers connecting the most medial part of the precentral gyrus. Fibers originating from the anterior bank of the central sulcus were invariably found to be located in the isthmus of the corpus callosum, and no leg motor fibers were found in the anterior part of the callosum. The current results suggest that the disconnection of the pre-splenial fibers, located in the posterior one-third of the corpus callosum, is paramount in obtaining a good outcome after callosotomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00429-015-1167-8DOI Listing
January 2017

Improving first responders' psychogenic nonepileptic seizures diagnosis accuracy: Development and validation of a 6-item bedside diagnostic tool.

Epilepsy Behav 2016 Jan 29;54:40-6. Epub 2015 Nov 29.

Psychiatry Department, Brown Medical School, Rhode Island Hospital, Providence, RI, USA; Neurology Department, Brown Medical School, Rhode Island Hospital, Providence, RI, USA.

Objective: Epileptic seizures (ES) are often seen as a medical emergency, and their immediate and accurate recognition are pivotal in providing acute care. However, a number of clinical situations may mimic ES, potentially leading to misdiagnosis at the emergency room and to inappropriate prescription of antiepileptic drugs (AED) in the acute and chronic settings. Psychogenic nonepileptic seizures (PNES) play a major role in this scenario and often delay the correct diagnosis and increase treatment morbidity and cost. First responders often conduct the initial assessment of these patients, and their impression may be decisive in the prehospital approach to seizures. We sought to investigate and improve the accuracy of PNES diagnosis among professionals involved in the initial assistance to patients with seizures.

Methods: Fifty-three registered nurses, 34 emergency physicians, 33 senior year medical students, and 12 neurology residents took a short training program consisting of an initial video-based seizure assessment test (pretest), immediately followed by a 30-minute presentation of a 6-item bedside diagnostic tool and then a video-based reassessment (posttest). Baseline status and learning curves were determined.

Results: The distinct professional categories showed no significant differences in their ability to diagnose PNES on both pretests and posttests. All groups improved diagnostic skills after the instructional program.

Significance: The findings helped determine the best identifiable PNES clinical signs and to provide initial validation to a novel diagnostic instrument. In addition, our results showed that educational measures might help in the identification of PNES by first responders, which may decrease the treatment gap.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2015.10.025DOI Listing
January 2016

Acute post-infectious cerebellitis.

Arq Neuropsiquiatr 2015 Nov 6;73(11):977. Epub 2015 Oct 6.

Departamento de Neurologia, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/0004-282X20150143DOI Listing
November 2015

Periodic lateralized epileptiform discharges (PLEDs) in herpetic encephalitis.

Arq Neuropsiquiatr 2015 Dec 6;73(12):1046. Epub 2015 Oct 6.

Departamento de Medicina Interna / Neurologia, Faculdade de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1590/0004-282X20150149DOI Listing
December 2015

Dysplastic Cerebellar Epilepsy: Complete Seizure Control Following Resection of a Ganglioglioma.

Cerebellum 2016 Aug;15(4):535-41

Severe Epilepsies Outpatient Clinic, Neurology Service, Hospital São Lucas, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Avenida Ipiranga 6690, 90610-000, Porto Alegre, RS, Brazil.

Subcortical epilepsy has been a controversial issue, partially settled by evidence showing seizure generation in hypothalamic hamartomas and also by reports of seizures caused by cerebellar lesions. We report 4-year-old girl with right hemifacial seizures and autonomic phenomena, in whom MRI showed an irregular mass in the right cerebellar peduncle. Despite several unremarkable video-EEG recordings, seizure origin in the lesion was hypothesized. Complete resection was feasible, histopathology showed a ganglioglioma, and she has been seizure free for 3 years. A fine line separates these developmental tumors from focal cortical dysplasia, and the homogeneous presentation of this entity led us to propose the terminology dysplastic cerebellar epilepsy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12311-015-0705-5DOI Listing
August 2016

Methylphenidate improves the quality of life of children and adolescents with ADHD and difficult-to-treat epilepsies.

Epilepsy Behav 2015 May 1;46:215-20. Epub 2015 May 1.

Severe and Refractory Epilepsies Outpatient Clinic, Neurology Service, Hospital São Lucas, Faculty of Medicine, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil.

Objective: Comorbidity between difficult-to-treat epilepsies and ADHD is frequent and impacts negatively on quality of life. The commonly held (yet poorly substantiated) view that stimulants may worsen seizure control has prevented studies from evaluating the impact of such treatment in this population. Our aim was to study the effect of methylphenidate on the quality of life of children and adolescents with difficult-to-treat epilepsies and comorbid ADHD.

Methods: The study was an open-label, noncontrolled trial with intention-to-treat analysis following 30 patients for 6months. Subjects received methylphenidate following 3months of baseline, during which antiepileptic drugs (AEDs) were adjusted and epilepsy, ADHD, and quality-of-life variables were assessed. Multivariate regression analysis identified the main variables correlated with outcome.

Results: Only one patient withdrew because of seizure worsening. Following methylphenidate introduction, doses were titrated up to 0.40-0.50mg/kg/day. A marked improvement in quality-of-life scores and a significant reduction in seizure frequency and severity were observed. Female sex, reduction of core ADHD symptoms, and tolerability to adequate doses of methylphenidate were significantly associated with improved quality-of-life scores.

Conclusion: These preliminary data suggest that methylphenidate treatment is safe and effective in patients with ADHD and difficult-to-treat epilepsies, positively impacting on quality-of-life scores.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yebeh.2015.02.019DOI Listing
May 2015

"Mirror EPC": epilepsia partialis continua shifting sides after rolandic resection in dysplasia.

Neurology 2014 Oct 12;83(16):1439-43. Epub 2014 Sep 12.

From the Service of Neurology (M.H., J.C.d.C., W.A.M., M.L.N., A.P.), Service of Neurosurgery (E.P.), Porto Alegre Epilepsy Surgery Program (M.H., E.P., J.C.d.C., A.P.), Department of Internal Medicine, Division of Neurology (J.C.d.C., M.L.N., A.P.), Department of Surgery (E.P.), The Brain Institute (InsCer) (J.C.d.C., M.L.N.), Pontificia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil; and Montreal Neurological Institute (F.D., F.A., A.O.), Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.

Background: Epilepsia partialis continua (EPC) is a life-threatening condition often caused by focal cortical dysplasia (FCD). Resection of the motor cortex is contemplated in the hope that the trade-off between a severe motor deficit and complete seizure control justifies the procedure.

Methods: Report of 3 patients with EPC due to histologically confirmed FCD, who underwent resection of the motor cortex under acute electrocorticography.

Results: All had re-emergence of medically intractable EPC in the other side of the body after rolandic resection. Two patients died and the third continues with refractory attacks.

Conclusion: In some instances, EPC due to FCD may shift sides and re-emerge in the contralateral, previously asymptomatic, hemibody. A mechanism of disinhibition by surgery of a suppressed contralateral and homologous epileptogenic zone is speculated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000000878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4206162PMC
October 2014