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1.
J Neurol Neurosurg Psychiatry ; 92(3): 291-294, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33219046

RESUMO

OBJECTIVE: To generate a score which clinically identifies surface-directed autoantibodies in adults with new-onset focal epilepsy, and evaluate the value of immunotherapy in this clinical setting. METHODS: Prospective clinical and autoantibody evaluations in a cohort of 219 consecutive patients with new-onset focal epilepsy. RESULTS: 10.5% (23/219) of people with new-onset focal epilepsy had detectable serum autoantibodies to known or novel cell surface antigenic targets. 9/23 with autoantibodies were diagnosed with encephalitis, by contrast to 0/196 without autoantibodies (p<0.0001). Multivariate analysis identified six features which predicted autoantibody positivity (area under the curve=0.83): age ≥54 years, ictal piloerection, lowered self-reported mood, reduced attention, MRI limbic system changes and the absence of conventional epilepsy risk factors. 11/14 (79%) patients with detectable autoantibodies, but without encephalitis, showed excellent long-term outcomes (modified Rankin Score=0) despite no immunotherapy. These outcomes were superior to those of immunotherapy-treated patients with confirmed autoantibody-mediated encephalitis (p<0.05). CONCLUSIONS: Seizure semiology, cognitive and mood phenotypes, alongside inflammatory investigation findings, aid the identification of surface autoantibodies among unselected people with new-onset focal epilepsy. The excellent immunotherapy-independent outcomes of autoantibody-positive patients without encephalitis suggests immunotherapy administration should be guided by clinical features of encephalitis, rather than autoantibody positivity. Our findings suggest that, in this cohort, immunotherapy-responsive seizure syndromes with autoantibodies largely fall under the umbrella of autoimmune encephalitis.


Assuntos
Autoanticorpos/sangue , Epilepsias Parciais/sangue , Epilepsias Parciais/imunologia , Imunoterapia , Proteínas do Tecido Nervoso/imunologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Encefalite/sangue , Encefalite/etiologia , Epilepsias Parciais/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Adulto Jovem
2.
Epilepsy Behav ; 116: 107684, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33545648

RESUMO

OBJECTIVES: Our primary objective was to better discern features that can differentiate people with 'mixed' symptomatology from those who experience epileptic seizures (ES) or functional/psychogenic nonepileptic seizures (PNES) alone, in a population of patients referred for video-telemetry. We wished to see if we could establish the prevalence of PNES in this population of interest as well as compare both objective (e.g. videotelemetry reports and heart rate measurements) and subjective, patient-centered measures (reported symptoms and experiences). METHODS: Data were sourced from a database of all video-telemetry patients admitted to the John Radcliffe Hospital (Oxford, UK) between 1st Jan 2014 and 31st Jan 2016; video-electroencephalogram (vEEG) reports for the above patients; neurology clinic letters; multidisciplinary Team (MDT) reports; psychology assessments and patient notes for all vEEG patients referred for surgical work up. Mixed cases with a dual ES/PNES diagnosis were carefully evaluated again by the Consultant Neurologist under whose care each respective patient was, through case-by-case evaluation of EEG and telemetry reports. We compared mean heart rate during attacks captured on vEEG, number of physical symptoms reported, episode length, and postictal confusion between the three groups (ES; PNES; ES and PNES (mixed)). We evaluated the groups in terms of demographic and psychological parameters as well as prescription of anti-seizure medication. Pearson correlation significance was examined at 95% level of significance for p-values corrected for multiple comparisons. RESULTS: Overall, mixed cases reported experiencing a significantly lower number of physical symptoms compared to PNES cases (p = 0.018). The heart rate of PNES cases was significantly lower than that of mixed cases during the attacks (p = 0.003). ES patients exhibited the highest heart rate of all three groups and a greater degree of postictal confusion (adjusted p = 0.003 and p < 0.001, respectively) compared to those with PNES. There was no statistically significant difference in episode length between mixed and ES cases, while PNES patients had significantly longer episode duration (p = 0.021) compared to the mixed group. We noted that 81.6% of PNES patients were taking at least one anti-seizure medication. CONCLUSION: Patients with mixed seizures seem to be part of a spectrum between ES and PNES cases. Mixed cases are more similar to the ES group with regard to episode length and number of symptoms reported. In the PNES cohort, we found an over-reporting of ictal symptoms (e.g. palpitations, diaphoresis) disproportionate to recorded heart rate, which is lower in PNES than in epileptic attacks. This seems consistent with PNES cases experiencing a degree of impaired interoceptive processing, as part of a functional disorder spectrum. We noted that there was tendency for overmedication in the PNES group. The need for 'de-prescribing' should be addressed with measures that include better liaison with the community care team. With regard to potential autonomic dysregulation in the mixed cases, it might be interesting to see if vagus nerve stimulation could be accompanied by normalization of cardiovascular physiology parameters for people with both epileptic and psychogenic nonepileptic seizures.


Assuntos
Epilepsia , Transtornos Mentais , Eletroencefalografia , Epilepsia/diagnóstico , Frequência Cardíaca , Humanos , Convulsões/diagnóstico
3.
Epilepsy Behav ; 116: 107738, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33517199

RESUMO

About 30% of people with epilepsy (PWE) are drug-resistant. Those with focal seizures may be suitable for epilepsy surgery. Those not amenable to resective surgery can be considered for vagus nerve stimulation (VNS). However, after operative procedures, around 50% of patients continue to experience seizures. A multi-center retrospective study assessing perampanel effectiveness and tolerability for PWE who have undergone surgical resection and/or VNS implantation was performed. The primary outcome was ≥50% reduction in seizure frequency while secondary outcomes included side effects (SEs), dose-related effectiveness, and toxicity. The median perampanel dose was 6 mg. Only one PWE became seizure free. A ≥50% decrease in seizure frequency was observed in 52.8% of the post-resection group and 16.9% of the VNS group (p < 0.001), while SEs were seen in 44.8% and 41.1%, respectively. Perampanel doses greater than 8 mg led to better response in both groups, especially in the post-VNS cohort. SEs were not dose-related and the safety profile was similar to previous observational studies. Perampanel can be beneficial in these two super-refractory epilepsy groups, particularly in PWE with seizures after surgical resection. Doses of more than 8 mg appear to be well tolerated and may be more effective than lower doses in PWE after surgical interventions.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Estimulação do Nervo Vago , Epilepsia Resistente a Medicamentos/terapia , Epilepsia/terapia , Humanos , Nitrilas , Piridonas , Estudos Retrospectivos , Resultado do Tratamento
4.
Hippocampus ; 29(2): 63-67, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30069971

RESUMO

Classical views of the medial temporal lobe (MTL) have established that it plays a crucial role in long-term memory (LTM). Here we demonstrate, in a sample of patients who have undergone anterior temporal lobectomy for the treatment of pharmacoresistant epilepsy, that the MTL additionally plays a specific, causal role in short-term memory (STM). Patients (n=22) and age-matched healthy control participants (n=26) performed a STM task with a sensitive continuous report measure. This paradigm allowed us to examine recall memory for object identity, location and object-location binding, independently on a trial-by-trial basis. Our findings point to a specific involvement of MTL in object-location binding, but, crucially, not retention of either object identity or location. Therefore the MTL appears to perform a specific computation: binding disparate features that belong to a memory. These results echo findings from previous studies, which have identified a role for the MTL in relational binding for LTM, and support the proposal that MTL regions perform such a function for both STM and LTM, independent of the retention duration. Furthermore, these findings and the methodology employed here may provide a simple, sensitive and clinically valuable means to test memory dysfunuction in MTL disorders.


Assuntos
Lobectomia Temporal Anterior/tendências , Memória de Curto Prazo/fisiologia , Desempenho Psicomotor/fisiologia , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiologia , Adulto , Lobectomia Temporal Anterior/efeitos adversos , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
5.
Epilepsia ; 59(7): 1410-1420, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29901232

RESUMO

OBJECTIVE: There is little detailed phenotypic characterization of bilateral hippocampal sclerosis (HS). We therefore conducted a multicenter review of people with pharmacoresistant epilepsy and bilateral HS to better determine their clinical characteristics. METHODS: Databases from 11 EPIGEN centers were searched. For identified cases, clinicians reviewed the medical notes, imaging, and electroencephalographic (EEG), video-EEG, and neuropsychometric data. Data were irretrievably anonymized, and a single database was populated to capture all phenotypic information. These data were compared with phenotyped cases of unilateral HS from the same centers. RESULTS: In total, 96 patients with pharmacoresistant epilepsy and bilateral HS were identified (43 female, 53 male; age range = 8-80 years). Twenty-five percent had experienced febrile convulsions, and 27% of patients had experienced status epilepticus. The mean number of previously tried antiepileptic drugs was 5.32, and the average number of currently prescribed medications was 2.99; 44.8% of patients had cognitive difficulties, and 47.9% had psychiatric comorbidity; 35.4% (34/96) of patients continued with long-term medical therapy alone, another 4 being seizure-free on medication. Sixteen patients proceeded to, or were awaiting, neurostimulation, and 11 underwent surgical resection. One patient was rendered seizure-free postresection, with an improvement in seizures for 3 other cases. By comparison, of 201 patients with unilateral HS, a significantly higher number (44.3%) had febrile convulsions and only 11.4% had experienced status epilepticus. Importantly, 41.8% (84/201) of patients with unilateral HS had focal aware seizures, whereas such seizures were less frequently observed in people with bilateral HS, and were never observed exclusively (P = .002; Fisher's exact test). SIGNIFICANCE: The current work describes the phenotypic spectrum of people with pharmacoresistant epilepsy and bilateral HS, highlights salient clinical differences from patients with unilateral HS, and provides a large platform from which to develop further studies, both epidemiological and genomic, to better understand etiopathogenesis and optimal treatment regimes in this condition.


Assuntos
Dominância Cerebral/fisiologia , Epilepsia Resistente a Medicamentos/fisiopatologia , Epilepsias Parciais/fisiopatologia , Hipocampo/patologia , Fenótipo , Estado Epiléptico/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/cirurgia , Feminino , Hipocampo/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Esclerose , Estado Epiléptico/diagnóstico , Estado Epiléptico/cirurgia , Adulto Jovem
6.
J Neurol Neurosurg Psychiatry ; 88(4): 353-361, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28115470

RESUMO

OBJECTIVES: Autoantibodies against the extracellular domains of the voltage-gated potassium channel (VGKC) complex proteins, leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-2 (CASPR2), are found in patients with limbic encephalitis, faciobrachial dystonic seizures, Morvan's syndrome and neuromyotonia. However, in routine testing, VGKC complex antibodies without LGI1 or CASPR2 reactivities (double-negative) are more common than LGI1 or CASPR2 specificities. Therefore, the target(s) and clinical associations of double-negative antibodies need to be determined. METHODS: Sera (n=1131) from several clinically defined cohorts were tested for IgG radioimmunoprecipitation of radioiodinated α-dendrotoxin (125I-αDTX)-labelled VGKC complexes from mammalian brain extracts. Positive samples were systematically tested for live hippocampal neuron reactivity, IgG precipitation of 125I-αDTX and 125I-αDTX-labelled Kv1 subunits, and by cell-based assays which expressed Kv1 subunits, LGI1 and CASPR2. RESULTS: VGKC complex antibodies were found in 162 of 1131 (14%) sera. 90 of these (56%) had antibodies targeting the extracellular domains of LGI1 or CASPR2. Of the remaining 72 double-negative sera, 10 (14%) immunoprecipitated 125I-αDTX itself, and 27 (38%) bound to solubilised co-expressed Kv1.1/1.2/1.6 subunits and/or Kv1.2 subunits alone, at levels proportionate to VGKC complex antibody levels (r=0.57, p=0.0017). The sera with LGI1 and CASPR2 antibodies immunoprecipitated neither preparation. None of the 27 Kv1-precipitating samples bound live hippocampal neurons or Kv1 extracellular domains, but 16 (59%) bound to permeabilised Kv1-expressing human embryonic kidney 293T cells. These intracellular Kv1 antibodies mainly associated with non-immune disease aetiologies, poor longitudinal clinical-serological correlations and a limited immunotherapy response. CONCLUSIONS: Double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits and occasionally against non-mammalian αDTX. These antibodies should no longer be classified as neuronal-surface antibodies. They consequently lack pathogenic potential and do not in themselves support the use of immunotherapies.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes do Sistema Nervoso/imunologia , Encefalopatias/imunologia , Doenças Neuromusculares/imunologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Encéfalo/imunologia , Encefalopatias/diagnóstico , Estudos de Coortes , Citosol/imunologia , Venenos Elapídicos/imunologia , Epitopos/imunologia , Células HEK293/imunologia , Hipocampo/imunologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Espaço Intracelular/imunologia , Radioisótopos do Iodo , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , Neurônios/imunologia , Proteínas/imunologia , Superfamília Shaker de Canais de Potássio/imunologia
7.
Cereb Cortex ; 25(11): 4584-95, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26009613

RESUMO

Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage.


Assuntos
Lesões Encefálicas/complicações , Lesões Encefálicas/patologia , Córtex Cerebral/fisiopatologia , Transtornos da Memória/etiologia , Memória de Curto Prazo/fisiologia , Lobo Temporal/patologia , Tálamo/fisiopatologia , Adolescente , Adulto , Estudos de Coortes , Imagem de Difusão por Ressonância Magnética , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Hipocampo/irrigação sanguínea , Hipocampo/patologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Vias Neurais/irrigação sanguínea , Vias Neurais/patologia , Testes Neuropsicológicos , Oxigênio/sangue , Adulto Jovem
8.
J Neurosci ; 34(14): 4920-8, 2014 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-24695711

RESUMO

In the healthy human brain, evidence for dissociable memory networks along the anterior-posterior axis of the hippocampus suggests that this structure may not function as a unitary entity. Failure to consider these functional divisions may explain diverging results among studies of memory adaptation in disease. Using task-based and resting functional MRI, we show that chronic seizures disrupting the anterior medial temporal lobe (MTL) preserve anterior and posterior hippocampal-cortical dissociations, but alter signaling between these and other key brain regions. During performance of a memory encoding task, we found reduced neural activity in human patients with unilateral temporal lobe epilepsy relative to age-matched healthy controls, but no upregulation of fMRI signal in unaffected hippocampal subregions. Instead, patients showed aberrant resting fMRI connectivity within anterior and posterior hippocampal-cortical networks, which was associated with memory decline, distinguishing memory-intact from memory-impaired patients. Our results highlight a critical role for intact hippocampo-cortical functional communication in memory and provide evidence that chronic injury-induced functional reorganization in the diseased MTL is behavioral inefficient.


Assuntos
Epilepsia do Lobo Temporal/complicações , Hipocampo/fisiopatologia , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Rede Nervosa/fisiopatologia , Adolescente , Adulto , Mapeamento Encefálico , Feminino , Hipocampo/irrigação sanguínea , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Rede Nervosa/irrigação sanguínea , Testes Neuropsicológicos , Oxigênio/sangue , Descanso , Estatística como Assunto , Estatísticas não Paramétricas , Adulto Jovem
9.
Epilepsy Behav ; 37: 221-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25068915

RESUMO

Medical students are increasingly turning to the website YouTube as a learning resource. This study set out to determine whether the videos on YouTube accurately depict the type of seizures that a medical student may search for. Two consultant epileptologists independently assessed the top YouTube videos returned following searches for eight terms relating to different categories of seizures. The videos were rated for their technical quality, concordance of diagnosis with an epileptologist-assigned diagnosis, and efficacy as a learning tool for medical education. Of the 200 videos assessed, 106 (63%) met the inclusion criteria for further analysis. Technical quality was generally good and only interfered with the diagnostic process in 8.5% of the videos. Of the included videos, 40.6-46.2% were judged to depict the purported diagnosis with moderate agreement between raters (75% agreement, κ=0.50). Of the videos returned after searching "tonic-clonic seizure", 28.6-35.7% were judged to show nonepileptic seizures with almost perfect interrater agreement (92.9% agreement, κ=0.84). Of the videos returned following the search "pseudoseizure", 77.8-88.9% of videos were judged to show nonepileptic seizures with substantial agreement (88.9% agreement, κ=0.61). Across all search terms, 19.8-33% of videos were judged as potentially useful as a learning resource, with fair agreement between raters (75.5% agreement, κ=0.38). These findings suggest that the majority of videos on YouTube claiming to show specific seizure subtypes are inaccurate, and YouTube should not be recommended as a learning tool for students. However, a small group of videos provides excellent demonstrations of tonic-clonic and nonepileptic seizures, which could be used by an expert teacher to demonstrate the difference between epileptic and nonepileptic seizures.


Assuntos
Educação Médica/métodos , Epilepsia Tônico-Clônica/diagnóstico , Internet , Aprendizagem , Convulsões/diagnóstico , Diagnóstico Diferencial , Humanos , Variações Dependentes do Observador , Estudantes de Medicina , Gravação em Vídeo
10.
Pract Neurol ; 12(4): 234-7, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22869765

RESUMO

We present a 19-year-old woman with severe encephalitis and raised intracranial pressure requiring decompressive craniectomy. Her clinical features were consistent with encephalitis in the context of acute primary Epstein-Barr virus (EBV) infection (infectious mononucleosis). Serology, bone marrow aspirate and PCR of blood and cerebrospinal fluid confirmed the diagnosis. She was treated with corticosteroids and aciclovir. She was critically unwell for 3 weeks, requiring artificial ventilation but eventually made a good recovery. EBV encephalitis is uncommon, making the diagnosis and decisions about clinical management challenging.


Assuntos
Aciclovir/administração & dosagem , Corticosteroides/administração & dosagem , Craniectomia Descompressiva , Encefalite Viral/terapia , Infecções por Vírus Epstein-Barr/terapia , Antivirais/administração & dosagem , Craniectomia Descompressiva/métodos , Gerenciamento Clínico , Encefalite Viral/diagnóstico , Infecções por Vírus Epstein-Barr/diagnóstico , Feminino , Humanos , Resultado do Tratamento , Adulto Jovem
11.
Pract Neurol ; 10(1): 34-8, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20130295

RESUMO

A 49-year-old white man returned urgently to the UK after spending 3 months in Goa. He had a several week history of vomiting, weight loss, a widespread desquamating skin rash, and symptoms and signs of a progressive painful sensorimotor neuropathy. He had a mild normocytic anaemia and lymphopenia. Nerve conduction studies revealed a severe predominantly axonal large fibre sensorimotor neuropathy, confirmed on subsequent sural nerve biopsy. Once he had left Goa most of his symptoms started to rapidly settle although the neuropathic symptoms remained severe. Arsenic poisoning was suspected. A spot urine arsenic concentration was 300 microg/l, confirming the diagnosis. He was treated with chelation therapy. Deliberate arsenic poisoning was highly likely.


Assuntos
Intoxicação por Arsênico/patologia , Intoxicação por Arsênico/fisiopatologia , Nervos Periféricos/fisiopatologia , Intoxicação por Arsênico/terapia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Nervo Sural/patologia
12.
Seizure ; 75: 174-184, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31757748

RESUMO

INTRODUCTION: Literature on New-Onset Refractory Status Epilepticus (NORSE) is scarce and management is guided mainly by retrospective reports, short case series or expert opinions. We aimed to add to the pool of the available data by retrospectively reviewing seven cases of NORSE cases admitted to our hospital over the last five years between January 2014 and March 2019. METHODS: Fully anonymised data from medical charts, EEG reports, imaging reports, laboratory test results, types of antiepileptic medications, intravenous anaesthetic therapy, and immune therapies received was collected, along with response to treatment, length of hospital stay and outcome at discharge. RESULTS: The mean age was 43.5 ±â€¯23.8 years (range 18-75) and three patients were females. Prodromal symptoms consisted mainly of fever (4/7), headache (4/7) and self terminating seizures (7/7), before presenting with status epilepticus. Initial imaging findings were abnormal in 3/7 and CSF analysis in 3/7. All patients underwent intermittent EEG recordings, mainly for titration or tapering of the anaesthetic agents, with the initial goal of achieving burst suppression and cessation of electrographic seizures. Our index case spent the longest time in therapeutic burst suppression (102 days) and remained on thiopentone for 214 days. The mean duration of NICU stay was 88 ±â€¯85.4 days (range 4-225 days) while the mean duration of hospital stay was 113.8 ±â€¯111.2 days (range 17-292). CONCLUSIONS: The management of patients with NORSE remains challenging, often requiring multiple intravenous anaesthetic treatments, leading to complicated and prolonged hospital and intensive care unit stays but good outcome remains possible.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/fisiopatologia , Tempo de Internação/tendências , Estado Epiléptico/diagnóstico , Estado Epiléptico/fisiopatologia , Adolescente , Adulto , Idoso , Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/terapia , Eletroencefalografia/métodos , Eletroencefalografia/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estado Epiléptico/terapia , Adulto Jovem
13.
Hum Brain Mapp ; 30(12): 4070-81, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19517529

RESUMO

Understanding functional plasticity in memory networks associated with temporal lobe epilepsy (TLE) is central to predicting memory decline following surgery. However, the extent of functional reorganization within memory networks remains unclear. In this preliminary study, we used novel analysis methods assessing network-level changes across the brain during memory task performance in patients with TLE to test the hypothesis that hippocampal functions may not readily shift between hemispheres, but instead may show altered intra-hemispheric organization with unilateral damage. In addition, we wished to relate functional differences to structural changes along specific fibre pathways associated with memory function. Nine pre-operative patients with intractable left TLE and 10 healthy controls underwent functional MRI during complex scene encoding. Diffusion tensor imaging was additionally performed in the same patients. In our study, we found no evidence of inter-hemispheric shifts in memory-related activity in TLE using standard general linear model analysis. However, tensor independent component analysis revealed significant reductions in functional connectivity between bilateral MTL, occipital and left orbitofrontal regions among others in left TLE. This altered orbitofrontal activity was directly related to measures of fornix tract coherence in patients (P < 0.05). Our results suggest that specific fibre pathways, potentially affected by MTL neurodegeneration, may play a central role in functional plasticity in TLE and highlight the importance of network-based analysis approaches. Relative to standard model-based methods, novel objective functional connectivity analyses may offer improved sensitivity to subtle changes in the distribution of memory functions relevant for surgical planning in TLE.


Assuntos
Mapeamento Encefálico , Epilepsia do Lobo Temporal/fisiopatologia , Lateralidade Funcional/fisiologia , Memória/fisiologia , Rede Nervosa/fisiopatologia , Adolescente , Adulto , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Plasticidade Neuronal/fisiologia
14.
Neuroimage Clin ; 24: 101952, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31357148

RESUMO

The occurrence of wide-scale neuroplasticity in the injured human brain raises hopes for biomarkers to guide personalised treatment. At the individual level, functional reorganisation has proven challenging to quantify using current techniques that are optimised for population-based analyses. In this cross-sectional study, we acquired functional MRI scans in 44 patients (22 men, 22 women, mean age: 39.4 ±â€¯14 years) with a language-dominant hemisphere brain tumour prior to surgery and 23 healthy volunteers (11 men, 12 women, mean age: 36.3 ±â€¯10.9 years) during performance of a verbal fluency task. We applied a recently developed approach to characterise the normal range of functional connectivity patterns during task performance in healthy controls. Next, we statistically quantified differences from the normal in individual patients and evaluated factors driving these differences. We show that the functional connectivity of brain regions involved in language fluency identifies "fingerprints" of brain plasticity in individual patients, not detected using standard task-evoked analyses. In contrast to healthy controls, patients with a tumour in their language dominant hemisphere showed highly variable fingerprints that uniquely distinguished individuals. Atypical fingerprints were influenced by tumour grade and tumour location relative to the typical fluency-activated network. Our findings show how alterations in brain networks can be visualised and statistically quantified from connectivity fingerprints in individual brains. We propose that connectivity fingerprints offer a statistical metric of individually-specific network organisation through which behaviourally-relevant adaptations could be formally quantified and monitored across individuals, treatments and time.


Assuntos
Mapeamento Encefálico/tendências , Encéfalo/diagnóstico por imagem , Idioma , Imageamento por Ressonância Magnética/tendências , Rede Nervosa/diagnóstico por imagem , Plasticidade Neuronal , Adulto , Idoso , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Estudos Transversais , Feminino , Humanos , Individualidade , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Estudos Prospectivos
15.
Seizure ; 69: 125-132, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31026743

RESUMO

PURPOSE: To explore the retention rates and the efficacy and tolerability of perampanel (PER) by using monthly real life data for a period of 12 months. METHODS: Longitudinal outcomes of (PER) usage were assessed using actuarial statistics in an observational nonrandomised multicentre study of 181 people with epilepsy (PWE) refractory to first and second line drugs. Graded seizure outcomes, toxicity and the dose of PER were recorded for each month. RESULTS: PWE were followed for a mean of 15.1 months. The total cumulative probability for retention on PER at 12 months was 61.7% and for ≥50% improvement was 38.2%. Most improvements in seizure control occurred soon after initiation of PER, 17% by one month, 32% by six months and 38% by twelve months, and mostly at low doses 53% on 2 mg and 90% up to 6 mg. Improvements, when they occurred, were sustained. The most common side effects were neuropsychiatric, occurring in 28%. The emergence of side effects did not appear to be dose related. Although people with intellectual disability (ID) were more likely to remain on PER they did not show improved seizure control and also reported more side effects. Patients treated with VNS and PER had a worse outcome. CONCLUSION: Overall around a third of people showed a useful, response to PER therapy. The response to PER is noted usually early in the treatment and for the majority of the patients for doses up to 8 mg.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Piridonas/uso terapêutico , Convulsões/tratamento farmacológico , Análise Atuarial , Adulto , Quimioterapia Combinada/métodos , Feminino , Humanos , Deficiência Intelectual , Masculino , Pessoa de Meia-Idade , Nitrilas , Estudos Retrospectivos , Resultado do Tratamento
16.
Sci Rep ; 7(1): 16138, 2017 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-29170537

RESUMO

Ultra high-field 7T MRI offers sensitivity to localize hippocampal pathology in temporal lobe epilepsy (TLE), but has rarely been evaluated in patients with normal-appearing clinical MRI. We applied multimodal 7T MRI to assess if focal subfield atrophy and deviations in brain metabolites characterize epileptic hippocampi. Twelve pre-surgical TLE patients (7 MRI-negative) and age-matched healthy volunteers were scanned at 7T. Hippocampal subfields were manually segmented from 600µm isotropic resolution susceptibility-weighted images. Hippocampal metabolite spectra were acquired to determine absolute concentrations of glutamate, glutamine, myo-inositol, NAA, creatine and choline. We performed case-controls analyses, using permutation testing, to identify abnormalities in hippocampal imaging measures in individual patients, for evaluation against clinical evidence of seizure lateralisation and neuropsychological memory test scores. Volume analyses identified hippocampal subfield atrophy in 9/12 patients (75%), commonly affecting CA3. 7/8 patients had altered metabolite concentrations, most showing reduced glutamine levels (62.5%). However, neither volume nor metabolite deviations consistently lateralized the epileptogenic hippocampus. Rather, lower subiculum volumes and glutamine concentrations correlated with impaired verbal memory performance. Hippocampal subfield and metabolic abnormalities detected at 7T appear to reflect pathophysiological processes beyond epileptogenesis. Despite limited diagnostic contributions, these markers show promise to help elucidate mnemonic processing in TLE.


Assuntos
Epilepsia do Lobo Temporal/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Adulto , Atrofia/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
17.
Neurosurgery ; 52(3): 545-52; discussion 550-2, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12590678

RESUMO

OBJECTIVE: We sought to determine the incidence of seizures among patients treated with endovascular coil embolization for ruptured intracranial aneurysms because data on which to base antiepileptic drug (AED) prescriptions and advice to patients regarding driving motor vehicles and other high-risk activities are currently lacking. METHODS: We conducted a single-institute, single-operator observational study of 243 patients referred for endovascular treatment after aneurysmal subarachnoid hemorrhage. Prospective data collection was performed, and all successfully treated patients were followed. The incidence of seizures was compared with published surgical data, and logistic regression analysis of potential clinical associations was performed. Patients were followed for up to 7.7 years (mean follow-up period, 21.9 mo). RESULTS: Ictal seizures occurred at the time of subarachnoid hemorrhage in 26 (11%) of 243 patients and correlated with middle cerebral artery aneurysm location, loss of consciousness at ictus, and AED prescription. No patients experienced periprocedural seizures during their hospitalization. Seven of 233 successfully treated patients (3%) experienced seizures more than 30 days after treatment: late seizures occurred de novo in four patients (1.7%) and in three patients (1.4%) were caused by preexisting epilepsy. Two patients (0.85%) who had de novo seizures developed epilepsy. Late seizures correlated with a history of previous seizures, the presence of a cerebrospinal fluid shunt, and the use of AEDs. CONCLUSION: The low incidence of seizures does not justify the use of prophylactic AED therapy after aneurysmal subarachnoid hemorrhage in patients treated solely with coil embolization, nor does it justify subsequent restrictions on the driving of motor vehicles if the patient is otherwise fit to drive.


Assuntos
Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Condução de Veículo , Embolização Terapêutica/efeitos adversos , Complicações Pós-Operatórias , Convulsões/etiologia , Convulsões/prevenção & controle , Hemorragia Subaracnóidea/terapia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Padrões de Prática Médica , Estudos Prospectivos , Convulsões/epidemiologia , Fatores de Tempo
18.
J Clin Neurophysiol ; 29(5): 397-407, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23027097

RESUMO

Occipital lobe epilepsies (OLEs) manifest with occipital seizures from an epileptic focus within the occipital lobes. Ictal clinical symptoms are mainly visual and oculomotor. Elementary visual hallucinations are common and characteristic. Postictal headache occurs in more than half of patients (epilepsy-migraine sequence). Electroencephalography (EEG) is of significant diagnostic value, but certain limitations should be recognized. Occipital spikes and/or occipital paroxysms either spontaneous or photically induced are the main interictal EEG abnormalities in idiopathic OLE. However, occipital epileptiform abnormalities may also occur without clinical relationship to seizures particularly in children. In cryptogenic/symptomatic OLE, unilateral posterior EEG slowing is more common than occipital spikes. In neurosurgical series of symptomatic OLE, interictal EEG abnormalities are rarely strictly occipital. The most common localization is in the posterior temporal regions and less than one-fifth show occipital spikes. In photosensitive OLE, intermittent photic stimulation elicits (1) spikes/polyspikes confined in the occipital regions or (2) generalized spikes/polyspikes with posterior emphasis. In ictal EEG, a well-localized unifocal rhythmic ictal discharge during occipital seizures is infrequent. A bioccipital field spread to the temporal regions is common. Frequency, severity, and response to treatment vary considerably from good to intractable and progressive mainly depending on underlying causes.


Assuntos
Mapeamento Encefálico/métodos , Ondas Encefálicas , Eletroencefalografia , Lobo Occipital/fisiopatologia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Ondas Encefálicas/efeitos dos fármacos , Criança , Pré-Escolar , Epilepsias Parciais/classificação , Epilepsias Parciais/diagnóstico , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/terapia , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Lobo Occipital/efeitos dos fármacos , Lobo Occipital/patologia , Lobo Occipital/cirurgia , Periodicidade , Valor Preditivo dos Testes , Resultado do Tratamento , Adulto Jovem
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