The ILAE consensus classification of focal cortical dysplasia: An update proposed by an ad hoc task force of the ILAE diagnostic methods commission

Ongoing challenges in diagnosing focal cortical dysplasia (FCD) mandate continuous research and consensus agreement to improve disease definition and classification. An International League Against Epilepsy (ILAE) Task Force (TF) reviewed the FCD classification of 2011 to identify existing gaps and provide a timely update. The following methodology was applied to achieve this goal: a survey of published literature indexed with ((Focal Cortical Dysplasia) AND (epilepsy)) between 01/01/2012 and 06/30/2021 (n = 1349) in PubMed identified the knowledge gained since 2012 and new developments in the field. An online survey consulted the ILAE community about the current use of the FCD classification scheme with 367 people answering. The TF performed an iterative clinico-pathological and genetic agreement study to objectively measure the diagnostic gap in blood/brain samples from 22 patients suspicious for FCD and submitted to epilepsy surgery. The literature confirmed new molecular-genetic characterizations involving the mechanistic Target Of Rapamycin (mTOR) pathway in FCD type II (FCDII), and SLC35A2 in mild malformations of cortical development (mMCDs) with oligodendroglial hyperplasia (MOGHE). The electro-clinical-imaging phenotypes and surgical outcomes were better defined and validated for FCDII. Little new information was acquired on clinical, histopathological, or genetic characteristics of FCD type I (FCDI) and FCD type III (FCDIII). The survey identified mMCDs, FCDI, and genetic characterization as fields for improvement in an updated classification. Our iterative clinico-pathological and genetic agreement study confirmed the importance of immunohistochemical staining, neuroimaging, and genetic tests to improve the diagnostic yield. The TF proposes to include mMCDs, MOGHE, and “no definite FCD on histopathology” as new categories in the updated FCD classification. The histopathological classification can be further augmented by advanced neuroimaging and genetic studies to comprehensively diagnose FCD subtypes; these different levels should then be integrated into a multi-layered diagnostic scheme. This update may help to foster multidisciplinary efforts toward a better understanding of FCD and the development of novel targeted treatment options

Professionally successful adults with attention-deficit/hyperactivity disorder (ADHD): Compensation strategies and subjective effects of pharmacological treatment

Abstract Although as a group, adult patients with ADHD have difficulties in social functioning due to inattention and executive dysfunction, some strive and succeed in living a productive, independent life. Purpose: To report on professionally successful adults with ADHD and analyze their main symptoms, compensation strategies and the subjective effect of methylphenidate on their functioning. Methods: The main symptoms of five patients with ADHD who are University educated and financially independent are reported. These patients were selected from a personally followed cohort of adults with ADHD. All were diagnosed according to DSM-IV adapted criteria (K-SADS E, version 6.0) and completed the Portuguese translated version of the ADHD adult self-reporting scale (ASRS). Results: Main reported symptoms included difficulties with attention, tendency to procrastinate and to 'shuffle' priorities, excessive daytime somnolence, memory difficulties and impulsiveness. Compensation strategies revolve around conscious, 'energy demanding' and time consuming efforts to control and circumvent symptomatic behavioral tendencies. They feel methylphenidate helps by alleviating the need to constantly apply compensation strategies for socially disabling symptoms. In sum, they achieve the same results in a more natural, less effortful fashion. Conclusions: Adults with ADHD may succeed professionally despite significant symptoms of inattention and executive dysfunction. They do so by appropriately using effortful strategies of compensation, the need for which is alleviated by the use of methylphenidate. These subjective reports require confirmation in prospective studies on larger series of patients

Displasias corticais associadas a epilepsia : delineamento de uma nova sindrome, revisão de conceitos localizacionais e proposta de uma nova classificação

Orientadores: Carlos Alberto Mantovani Guerreiro, Marilisa Mantovani GuerreiroTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: O advento de modernas técnicas de neuroimagem, particularmente da ressonância magnética (RM), tem permitido a identificação 'in vivo' de lesões displásicas em pacientes previamente diagnosticados como portadores de epilepsias criptogênicas. Estas lesões são heterogêneas do ponto de vista clínico, anatômico, histopatológico e fisiopatogênico, embora tal heterogeneidade não seja sistematicamente reconhecida, dificultando uma compreensão mais aprofundada do quadro clínico e da história natural dos diversos tipos de displasias corticais. Para determinar a relevância dos aspectos anatômicos e histopatológicos na apresentação clínico-eletrográfica das displasias corticais, identificar síndromes epilépticas específicas e reavaliar conceitos localizacionais, estudamos 99 pacientes com formas variadas porém bem caracterizadas de displasia cortical e 39 pacientes com crises refratárias associadas a lesões epileptogênicas extra-hipocampais não displásicas. Todos foram submetidos a intensa avaliação clínica, eletrográfica e de neuroimagem. Cinqüenta e três dos 78 pacientes (68%) com formas localizadas de displasia cortical foram operados e o diagnóstico histopatológico específico foi confirmado. N os restantes, o diagnóstico baseou-se nos estudos por RM, o mesmo ocorrendo nos 21 pacientes com displasias corticais difusas (síndrome do córtex duplo" - SCD). Todos os 39 pacientes com lesões extra-hipocampais não displásicas foram operados e o diagnóstico histopatológico foi confirmado. O grupo de 54 pacientes com displasias corticais focais tipo Taylor (DCFIT) ou com hemimegalencefalia (HMG) - os quais caracterizavam-se histologicamente pela presença de neurônios displásicos e células eIl). balão, e fisopatogenicamente por anormalidades do desenvolvimento das células corticais- apresentaram ocorrência, significativamente maior de statuS epilepticus (p=0,008); descargas epileptogênica~' contínuas ao EEG (DEC-EEG) (p=0,001) e de refratariedade aos fármacos antiepilépticos (p=0,0001) do que o grupo de 24 pacientes com polimicrogiria (PMG) e esquizencefalia (SCH), lesões estas que não apresentam as alterações celulares descritas acima e que provavelmente decorram de eventos destrutivos no telencéfalo em fOffi1ação. Dezesseis dos 78 pacientes (20%) com diversas formas localizadas de displasia cortical apresentaram episódios de epilepsia partialis continua (EPC). Este percentual elevou-se para 27% ao se restringir a análise especificamente aos 54 pacientes com DCFIT ou HMG. Por outro lado, apenas 3 dos 39 pacientes (7,6%) com lesões não displásicas apresentaram episódios de EPC, sendo que esta cifra reduzia-se para 2,7% (1/37) com a exclusão dos 2 pacientes deste grupo com encefalite crônica de Rasmussen (p=O,06). Os pacientes com displasia cortical e episódios de EPC apresentaram uma maior ocorrência de outros tipos de crises parciais motoras (p=O,0021; 0,0009), síndrome piramidal unilateral ao exame neurológico (p= 0,0001; 0,0003), envolvimento do córtex rolândico pela lesão (p=0,0001; 0,0005) e descargas epileptogênicas contínuas ao EEG (DEC-EEG) (p= 0,002; 0,0001) do que pacientes com displasia cortical sem EPC e também do que pacientes com lesões não-displásicas, respectivamente. Resultados cirúrgicos quanto ao controle das crises refratárias foram satisfatórios em 60% dos pacientes com displasia cortical e EPC, sendo que déficits motores apareceram ou acentuaram-se no pós-operatório em 50% dos casos. Quinze dos 54 pacientes com DCFIT /HMG (27%), mas somente um dos 24 com PMG/SCH (4%) apresentaram EPC, sugerindo uma associação entre o tipo histopatológico de displasia e a ocorrência desta síndrome. Entre 60 e 75% dos 21 pacientes com a "síndrome do córtex duplo" (SCD) apresentaram uma ou mais evidências de acentuação focal ou regional da disfunção epileptogênica, apesar da natureza difusa da alteração estrutural: crises parciais (61%), descargas epileptógenas focais ao EEG (67%) ou hipoperfusão localizada aos exames de tomografia computadorizada por emissão de fóton único (SPEcr) (75%; 8 pacientes estudados). A ocorrência de crises parciais e descargas focais ao EEG associaram-se significativamente entre si. Não houve associação entre indicadores de gravidade da heterotopia e evidências de acentuação focal do quadro epileptogênico. As observações realizadas. nesta série de 99 pacientes com formas variadas de displasia cortical sugerem que os padrões anatômicos, histopatológicos e fisiopatogênicos, associam-se a quadros clínico-eletrográficos distintos. Uma classificação englobando de uma forma clinicamente relevante dados anatômicos, histológicos e fisiopatogênicos, pôde então ser proposta, dividindo as displasias corticais em 4 categorias diagnósticas: (i) distúrbios primariamente da migração neuronal; (ii) distúrbios da migração neuronal secundários a insultos destrutivos do alinhamento do telencéfalo; (iii) distúrbios primariamente do desenvolvimento das células cortiçais; e (iv) formas mistas. Em conclusão, pacientes com Dcm ou HMG associam-se a indicadores de maior gravidade da epilepsia, incluindo a ocorrência de EPC, quando comparados a' pacientes com PMG ou SCH. Uma síndrome de EPC associada a displasias corticais pode ser delineada. Ela acomete aproximadamente 27% dos pacientes com fesões displásicas do tipo DCrn ou HMG, e caracteriza-se pela ocorrência nestes pacientes de outros tipos de crises parcias motor as, de anormalidades piramidais unilaterais, de lesões envolvendo o córtex rolândico e de DEC-EEG. Esta entidade responde favoravelmente ao tratamento cirúrgico em 60% dos casos, a despeito do aparecimento ou acentuação de déficits motores no pós-operatório. Uma revisão de conceitos localizacionais é sugerida para as formas difusas de displasia cortical como a SCD, uma vez que, a despeito da heterotopia ser usualmente bilateral e difusa, a maioria dos pacientes apresenta de acentuação focal do quadro epileptogênicoAbstract: Modemneuro:imagingtechniques current1y allows lin vivo I identification of cortical dysplastic lesions in patients previously thought to have cryptogenic epilepsies. These lesions constitute an heterogenous group of disorders from clinicall anatomical, histopathological, and pathogenetic standpoints. The fact that such heterogeneity is not readily realized often precludes a more detailed understanding of both the clinical manifestations and the natural history of specific types of cortical dysplastic lesions. With a view to determine whether anatomical and histopathological pictures are associated with particular clinico-electrographic presentations in patients with cortical dysplastic lesions; to identify specific epileptic syndromes; and to re-evaluate localizational concepts, we studied 99 patients with various types of cortical dysplastic lesions and 39 patients with refractory epilepsy associated with non-dysplastic, extra¬hippocampal epileptogenic lesions. Ali patients underwent detailed clinical, electrographic, and neuro:imaging evaluations. Fifty-three of the 78 patients (68%) with localized dysplastic lesions were operated and histopathologic diagnoses were confirmed. In the other 25, and also in the 21 patien~s with diffuse cortical dysplasia or the IIdouble cortex syndrome" (DCS), diagnosis was based on magnetic resonance (MR) :imaging studies. Ali 39 patients with non-dysplastic, extra-hippocampal epileptogenic lesions were operated and histopathological disgnoses were established. The 54 patients with Taylor type focal cortical dysplasia (DCFIT) or with hem:imegalencephaly (HMG) - whose histopathological picture was characterized by the presence of dysplastic neurons and ballon cells, and were thus considered to represent abnormalities of cortical cell development - had a significant1y higheroccurrence of a history of status epilepticus (p=0,008), of continuous epiletogenic discharges on EEG (DEC-EED)! (p=O,OOl), and of medical intractability (p=O,OOOl), in comparison with the 24 patients' with polymicrogyria (PMG) or schizencephaly (SCH). These latter entities do not display the histopathological elements described above, and are thought to represent destructive insults to the developing telencephalon. Sixteen of the 78 patients (20%) with a variety of types of localized dysplastic lesions had episodes of epilepsia partialis continua (EPC). This observation was furthermore increased to 27% when on1y the 54 patients with DCrIT or HMG were analyzed in this regard. In contrast, on1y 3 of 39 patients (7,6%) with non-dysplastic neocorticallesions had episodes of EPC. When the 2 patients with Rasmussen's chronic encephalitis were excluded from the analysis, then on1y 1 of 37 patients with non¬dysplastic neocorticallesions had EPC (p=0,06). Patients with cortical dysplasia and EPC had a significant1y higher occurrence of other types of partial motor seizures (p=0,0021; and 0,0009), of unilateral pyramidal syndrome on neurologic examination (p=O,OOOl; and 0,0003), of involvement of the rolandic cortex by the structural lesion (p= 0,0001 ; andO,0005 ), and of DEC-EEG (p=0,0002 ; and 0,0001 ) than patients with cortical dysplasia but without a history of episodes of EPC, and also than patients with neocortical Ron-dysplastic lesions, respectively. Surgi cal results in relation to seizure control were considered satisfactory in 60% of the patients with cortical dysplasia and EPC, but motor defucits emerged or accentuated in50% of the cases. Fifteen of the 54 patients with DCFTT /HMG (27%), but only one of the 24 with PMG/SCH (4%) had episodes of EPC, suggesting an association between the histopathological type of dysplasia and the occurrence of EPC. From 60 to 75% of the 21 patients with the double cortex syndrome (SCD) had one or more features suggestive of focal or regional accentuation of the epileptogenic dysfunction, despite the diffuse nature of the structural abnormality: partial seizures (61 % ), focal epileptiform abnormalities on EEG (67%), or localized hypoperfusion on single photon emission computed tomography (SPEcr) studies ( 75%; 6 of 8 patients thus studied). The occurrence of partial seizuers and of focal epileptiform abnormalities on EEG were significant1y associated with one another. There was no relationship between the severity of the heterotopia and clinical, electrographic, or imagingevidences of focal accentuation of the epileptogenic picture. The observations in this series of 99 patients with a variety of types of cortical dysplasia suggest that specific anatomic, histopathologic, and pathogenetic patterns are associated with distinct clinical-eletrographic pictures. A dassification encompassing in a c1inically relevant fashion anatomic, histological and pathogenentic data was then proposed, allocating the various types of cortical dysplasia in 4 diagnostic categories: (i) primary disorders of neuronal migration; (ii) disorders of neuronal migration secondary to destructive insults to the lining of the telencephalon; . (üi) primary disorders of cortical celL development; and (iv) mixed types. In conclusion, patients with DCFTT or HMG are associated with c1inical~, electrographic indicators of higher severity of the epileptogenic picture, including the occurrence of EPC, when compared to patients with PMG or SCH. A syndrome of EPC associated with cortical dysplasia was delineated. It affects approximately 27% of patients with dysplastic lesions of the DCFIT OF HMG types, and! is cna{'aeterizedl by the occurrence in these patients of other types of partial motor seizures, of trnilateral pyramidal abnormalities, of structurallesions involving the rolandic cortex, and of DEC-EEG. A favorable surgical outcome can be expected in about 60% of the patients, despite the fact that post-operative motor deficits may occur. A review of localizational concepts is suggested for the diffuse dysplastic lesions like the SCD. Despite the usually bilateral aRd diffuse nature of the heterotopia, most patients with SCD display evidence suggesting focal accentuation of the epileptogenic pictureDoutoradoNeurologiaDoutor em Ciências Médica

The impact of epilepsy on sleep architecture during childhood

Purpose: The effect of etiology on the relationship between epilepsy and sleep during childhood has not been studied in detail. The aim of this study was to evaluate differences in sleep structure in drug-resistant epilepsies with different underlying causes. Methods: We studied 31 patients with drug-resistant epilepsies with or without a structural lesion (lesional and nonlesional) and compared their sleep architecture with that of normal controls and with that of a group of children with benign epilepsy with rolandic spikes (BERS). Subjects underwent a single-night polysomnographic recording. Sleep recordings were scored according to the American Academy of Sleep Medicine (AASM) and cyclic alternating pattern (CAP) criteria. Key Findings: Compared to normal controls, patients with drug-resistant epilepsy showed a significant reduction of time in bed, total sleep time, rapid eye movement (REM) sleep, sleep stage N3, and sleep efficiency, and a significant increase in wake after sleep onset. The lesional subgroup showed a reduction in total sleep time and sleep latency and an increase in REM latency and wake after sleep onset. No significant differences, however, were found comparing the lesional and nonlesional subgroups. When compared to BERS, patients with drug-resistant epilepsy showed a significant reduction in sleep stage N3, REM sleep, and sleep efficiency. Regarding CAP analysis, when compared to controls, the drug-resistant group had an increased A1% and a decreased A2%, with a decrease of A1 index in N3 and a global decrease of A2 and A3 indexes. The lesional subgroup showed a slight increase of A1% with a decrease of A1 index in N3 and a global decrease of A2 and A3 indexes. Drug-resistant epilepsy, compared to benign epilepsy showed an increase of CAP rate in N2 and of A1 index in N1 and N2 but not in N3; A2 and A3 indexes were similar in both, but patients with drug-resistant epilepsy showed a significant reduction of A3 index in N1. Significance: Our findings suggest that the presence of structural cerebral abnormalities may play an important role in disrupting sleep architecture

Cognitive deficits during status epilepticus and time course of recovery: A case report

We describe a young woman with progressive cognitive and neurological deficits during a parietal lobe status epilepticus (SE). Ictal FDG-PET showed left parietal lobe hypermetabolism and frontal lobe hypornetabolism with concomitant EEG slowing. Cognitive and neurological deficits fully reversed more than I year after seizure remission, and were associated with normalization of FDG-PET and EEG. Our findings suggest that ictal hypometabolism and EEG delta activity at a distance from the epileptic focus were seizure-related phenomena, possibly representing inhibition in seizure propagation pathways, which could be responsible for the epileptic encephalopathy.status: publishe