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1.
Epilepsia ; 65(5): 1333-1345, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38400789

RESUMO

OBJECTIVE: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff. RESULTS: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months). SIGNIFICANCE: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques.


Assuntos
Benchmarking , Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/cirurgia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Criança , Pré-Escolar , Lactente , Complicações Pós-Operatórias/epidemiologia , Procedimentos Neurocirúrgicos/normas , Procedimentos Neurocirúrgicos/métodos , Epilepsia Resistente a Medicamentos/cirurgia , Lobectomia Temporal Anterior/métodos
2.
Epilepsia ; 64(9): 2249-2255, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37353891

RESUMO

Seizures resulting from cerebral autoimmunity are either acutely symptomatic in the context of autoimmune encephalitis (AIE) with neural surface antibodies, or they are indicative of an enduring predisposition to seizures, that is, epilepsy. Here, we propose a practical definition for autoimmune encephalitis-associated epilepsy (AEAE): Seizures associated with antibodies against glutamic acid decarboxylase, paraneoplastic syndromes, or Rasmussen encephalitis are classified as AEAE. AEAE secondary to AIE with antibodies against the N-methyl-D-aspartate receptor, leucine-rich glioma inactivated protein 1, contactin-associated protein-2, or γ-aminobutyric acid-B receptor can be diagnosed if the following criteria are met: seizures persist for at least 2 years after immunotherapy initiation; no signs of encephalitis on magnetic resonance imaging and no fluorodeoxyglucose positron emission tomography hypermetabolism; normal cerebrospinal fluid cell count; and a substantial decrease in antibody titers. This classification corresponds to different disease mechanisms. While AIE results from the pathogenic effects of neural antibodies, AEAE is probably the consequence of encephalitis-related tissue damage and thereby mainly structurally mediated. The distinction between AIE and AEAE also has practical consequences: In AIE, immunotherapy is usually highly beneficial, whereas anti-seizure medication has little effect. In AEAE, immunotherapy is less promising and the usual anti-seizure interventions are preferable. In addition, the diagnosis of AEAE has social consequences in terms of driving and professional limitations.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Epilepsia , Doença de Hashimoto , Humanos , Encefalite/complicações , Encefalite/diagnóstico , Encefalite/terapia , Epilepsia/etiologia , Epilepsia/complicações , Doença de Hashimoto/complicações , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/terapia , Doenças Autoimunes do Sistema Nervoso/complicações , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/terapia , Autoanticorpos
3.
J Neurol ; 271(9): 6325-6335, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39105896

RESUMO

Two-thirds of published patients with anti-leucine rich, glioma inactivated 1 (LGI1) encephalitis develop hippocampal sclerosis (HS). It is likely that this contributes to residual cognitive long-term deficits and the risk of epilepsy. Almost all patients harbor anti-LGI1-immunoglobulin G-(IgG-) subclass 4, which is considered a "benign", non-destructive subclass. In contrast, neuropathological case studies have suggested that the classical complement cascade may contribute to mediotemporal cell death in patients with LGI1 antibodies. IgG subclasses 1, 2, or 3 are required to initiate this cascade. We hypothesized that patients with these anti-LGI1-IgG1/2/3 in addition to IgG4 have a higher risk of developing HS than patients with anti-LGI1-IgG4 alone. We retrospectively assessed all anti-LGI1 encephalitis patients from this center with anti-LGI1-IgG-subclass information and follow-up MRI available. Nine out of 20 patients had developed HS (45%). Volumetric FreeSurfer analysis confirmed the visual HS diagnoses. HS and a lower hippocampal volume were associated with anti-LGI1-IgG1/2/3. All six patients with this IgG subclass status developed HS. There was no association with older or younger age at onset, female sex, longer latency from disease onset to start of immunotherapy, less intense immunotherapy, higher serum titers of LGI1 antibodies, LGI1 antibodies in CSF or higher LGI1-specific antibody indices. There was no association between anti-LGI1-IgG1/2/3 status and neuropsychological performance, epilepsy, or general neurological performance. This confirms our hypothesis that anti-LGI1-IgG1/2/3 in serum puts patients at risk of developing HS. If these findings can be confirmed and clinically corroborated, patients with anti-LGI1-IgG1/2/3 might become candidates for anti-complement-directed immunological treatments.


Assuntos
Autoanticorpos , Hipocampo , Imunoglobulina G , Peptídeos e Proteínas de Sinalização Intracelular , Esclerose , Humanos , Feminino , Masculino , Hipocampo/patologia , Esclerose/etiologia , Pessoa de Meia-Idade , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Imunoglobulina G/sangue , Idoso , Estudos Retrospectivos , Adulto , Encefalite/imunologia , Imageamento por Ressonância Magnética , Esclerose Hipocampal
4.
Neurol Neuroimmunol Neuroinflamm ; 11(4): e200225, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38838283

RESUMO

BACKGROUND AND OBJECTIVES: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. METHODS: This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. RESULTS: We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. DISCUSSION: Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.


Assuntos
Autoanticorpos , Encefalite , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Proteínas do Tecido Nervoso , Receptores de GABA-B , Recidiva , Humanos , Feminino , Masculino , Adulto , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Autoanticorpos/sangue , Pessoa de Meia-Idade , Encefalite/imunologia , Estudos Retrospectivos , Receptores de GABA-B/imunologia , Proteínas do Tecido Nervoso/imunologia , Adulto Jovem , Proteínas de Membrana/imunologia , Receptores de N-Metil-D-Aspartato/imunologia , Convulsões/etiologia , Convulsões/imunologia , Doença de Hashimoto/imunologia , Doença de Hashimoto/sangue , Idoso , Adolescente , Seguimentos , Proteínas/imunologia , Estudos de Coortes
5.
J Neurol ; 271(5): 2736-2744, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38386048

RESUMO

Autoantibodies against contactin-associated protein 2 (Caspr2) not only induce limbic autoimmune encephalitis but are also associated with pain conditions. Here, we analyzed clinical data on pain in a large cohort of patients included into the German Network for Research in Autoimmune Encephalitis. Out of 102 patients in our cohort, pain was a frequent symptom (36% of all patients), often severe (63.6% of the patients with pain) and/or even the major symptom (55.6% of the patients with pain). Pain phenotypes differed between patients. Cluster analysis revealed two major phenotypes including mostly distal-symmetric burning pain and widespread pain with myalgia and cramps. Almost all patients had IgG4 autoantibodies and some additional IgG1, 2, and/or 3 autoantibodies, but IgG subclasses, titers, and presence or absence of intrathecal synthesis were not associated with the occurrence of pain. However, certain pre-existing risk factors for chronic pain like diabetes mellitus, peripheral neuropathy, or preexisting chronic back pain tended to occur more frequently in patients with anti-Caspr2 autoantibodies and pain. Our data show that pain is a relevant symptom in patients with anti-Caspr2 autoantibodies and support the idea of decreased algesic thresholds leading to pain. Testing for anti-Caspr2 autoantibodies needs to be considered in patients with various pain phenotypes.


Assuntos
Autoanticorpos , Proteínas de Membrana , Proteínas do Tecido Nervoso , Fenótipo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autoanticorpos/sangue , Autoanticorpos/imunologia , Estudos de Coortes , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , Dor/imunologia , Dor/etiologia , Dor/sangue
6.
J Neurol ; 268(3): 1059-1069, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33025119

RESUMO

BACKGROUND: Clinicians have questioned whether any disorder involving seizures and neural antibodies should be called "(auto)immune epilepsy." The concept of "acute symptomatic seizures" may be more applicable in cases with antibodies against neural cell surface antigens. We aimed at determining the probability of achieving seizure-freedom, the use of anti-seizure medication (ASM), and immunotherapy in patients with either constellation. As a potential pathophysiological correlate, we analyzed antibody titer courses. METHODS: Retrospective cohort study of 39 patients with seizures and neural antibodies, follow-up ≥ 3 years. RESULTS: Patients had surface antibodies against the N-methyl-D-aspartate receptor (NMDAR, n = 6), leucine-rich glioma inactivated protein 1 (LGI1, n = 11), contactin-associated protein-2 (CASPR2, n = 8), or antibodies against the intracellular antigens glutamic acid decarboxylase 65 kDa (GAD65, n = 13) or Ma2 (n = 1). Patients with surface antibodies reached first seizure-freedom (88% vs. 7%, P < 0.001) and terminal seizure-freedom (80% vs. 7%, P < 0.001) more frequently. The time to first and terminal seizure-freedom and the time to freedom from ASM were shorter in the surface antibody group (Kaplan-Meier curves: P < 0.0001 for first seizure-freedom; P < 0.0001 for terminal seizure-freedom; P = 0.0042 for terminal ASM-freedom). Maximum ASM defined daily doses were higher in the groups with intracellular antibodies. Seizure-freedom was achieved after additional immunotherapy, not always accompanied by increased ASM doses. Titers of surface antibodies but not intracellular antibodies decreased over time. CONCLUSION: Seizures with surface antibodies should mostly be considered acute symptomatic and transient and not indicative of epilepsy. This has consequences for ASM prescription and social restrictions. Antibody titers correlate with clinical courses.


Assuntos
Antígenos de Superfície , Epilepsia , Autoanticorpos , Epilepsia/terapia , Humanos , Receptores de N-Metil-D-Aspartato , Estudos Retrospectivos , Convulsões
7.
Nat Commun ; 4: 1483, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23403584

RESUMO

The production of adequate agricultural outputs to support the growing human population places great demands on agriculture, especially in light of ever-greater restrictions on input resources. Sorghum is a drought-adapted cereal capable of reliable production where other cereals fail, and thus represents a good candidate to address food security as agricultural inputs of water and arable land grow scarce. A long-standing issue with sorghum grain is that it has an inherently lower digestibility. Here we show that a low-frequency allele type in the starch metabolic gene, pullulanase, is associated with increased digestibility, regardless of genotypic background. We also provide evidence that the beneficial allele type is not associated with deleterious pleiotropic effects in the modern field environment. We argue that increasing the digestibility of an adapted crop is a viable way forward towards addressing food security while maximizing water and land-use efficiency.


Assuntos
Adaptação Fisiológica/genética , Alelos , Secas , Abastecimento de Alimentos , Genes de Plantas/genética , Variação Genética , Sorghum/genética , Sequência de Aminoácidos , Grão Comestível/genética , Grão Comestível/fisiologia , Frequência do Gene/genética , Genótipo , Glicosídeo Hidrolases/química , Glicosídeo Hidrolases/genética , Humanos , Endogamia , Dados de Sequência Molecular , Mutação/genética , Peptídeos/química , Fenótipo , Estrutura Terciária de Proteína , Sorghum/fisiologia
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