Assuntos
Comportamento de Ingestão de Líquido/fisiologia , Encefalite Límbica/diagnóstico , Encefalite Límbica/fisiopatologia , Água , Idoso , Eletroencefalografia/métodos , Humanos , Hiponatremia/diagnóstico , Hiponatremia/psicologia , Agentes de Imunomodulação/uso terapêutico , Encefalite Límbica/tratamento farmacológico , Encefalite Límbica/psicologia , MasculinoRESUMO
OBJECTIVE: Limbic encephalitis (LE) comprises a spectrum of inflammatory changes in affected brain structures including the presence of autoantibodies and lymphoid cells. However, the potential of distinct lymphocyte subsets alone to elicit key clinicopathological sequelae of LE potentially inducing temporal lobe epilepsy (TLE) with chronic spontaneous seizures and hippocampal sclerosis (HS) is unresolved. METHODS: Here, we scrutinized pathogenic consequences emerging from CD8+ T cells targeting hippocampal neurons by recombinant adeno-associated virus-mediated expression of the model-autoantigen ovalbumin (OVA) in CA1 neurons of OT-I/RAG1-/- mice (termed "OVA-CD8+ LE model"). RESULTS: Viral-mediated antigen transfer caused dense CD8+ T cell infiltrates confined to the hippocampal formation starting on day 5 after virus transduction. Flow cytometry indicated priming of CD8+ T cells in brain-draining lymph nodes preceding hippocampal invasion. At the acute model stage, the inflammatory process was accompanied by frequent seizure activity and impairment of hippocampal memory skills. Magnetic resonance imaging scans at day 7 of the OVA-CD8+ LE model revealed hippocampal edema and blood-brain barrier disruption that converted into atrophy until day 40. CD8+ T cells specifically targeted OVA-expressing, SIINFEKL-H-2Kb -positive CA1 neurons and caused segmental apoptotic neurodegeneration, astrogliosis, and microglial activation. At the chronic model stage, mice exhibited spontaneous recurrent seizures and persisting memory deficits, and the sclerotic hippocampus was populated with CD8+ T cells escorted by NK cells. INTERPRETATION: These data indicate that a CD8+ T-cell-initiated attack of distinct hippocampal neurons is sufficient to induce LE converting into TLE-HS. Intriguingly, the role of CD8+ T cells exceeds neurotoxic effects and points to their major pathogenic role in TLE following LE. ANN NEUROL 2021;89:666-685.
Assuntos
Linfócitos T CD8-Positivos/patologia , Epilepsia do Lobo Temporal/etiologia , Epilepsia do Lobo Temporal/patologia , Encefalite Límbica/complicações , Encefalite Límbica/patologia , Animais , Barreira Hematoencefálica/patologia , Região CA1 Hipocampal/patologia , Epilepsia do Lobo Temporal/psicologia , Hipocampo/patologia , Proteínas de Homeodomínio/genética , Encefalite Límbica/psicologia , Linfonodos/patologia , Imageamento por Ressonância Magnética , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/patologia , Ovalbumina/genética , Ovalbumina/imunologia , Fragmentos de Peptídeos/genética , Convulsões/genética , Convulsões/patologiaRESUMO
Limbic encephalitis is often reported to present as seizures and impaired cognition with little focus on psychiatric presentations. In this case report, we present a 49-year-old man who initially presented to the Psychiatric Liaison Service with a several month history of confusion with the additional emergence of visual hallucinations and delusions. Due to the inconsistent nature of the symptoms in the context of a major financial stressor, a provisional functional cognitive impairment diagnosis was made. Investigations later revealed a positive titre of voltage-gated potassium channel (VGKC) antibodies, subtype leucine-rich glioma inactivated 1 accounting for his symptoms which dramatically resolved with steroids and immunoglobulins. This case highlighted the need for maintaining broad differential diagnoses in a patient presenting with unusual psychiatric symptoms.
Assuntos
Autoanticorpos/sangue , Disfunção Cognitiva/etiologia , Encefalite Límbica/diagnóstico , Encefalite Límbica/psicologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Anti-Inflamatórios/uso terapêutico , Confusão/etiologia , Delusões/etiologia , Diagnóstico Diferencial , Alucinações/etiologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Encefalite Límbica/tratamento farmacológico , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-IdadeRESUMO
There is clinical overlap between presentations of dementia due to limbic-predominant age-related TDP-43 encephalopathy (LATE) and Alzheimer's disease. It has been suggested that the combination of Alzheimer's disease neuropathological change (ADNC) and LATE neuropathological changes (LATE-NC) is associated with greater neuropsychiatric symptom burden, compared to either pathology alone. Longitudinal Neuropsychiatric Inventory and psychotropic medication prescription data from neuropathologically diagnosed pure ADNC (n = 78), pure LATE-NC (n = 14) and mixed ADNC/LATE-NC (n = 39) brain bank donors were analysed using analysis of variance and linear mixed effects regression models to examine the relationship between diagnostic group and neuropsychiatric symptom burden. Nearly all donors had dementia; three (two pure LATE-NC and one pure ADNC) donors had mild cognitive impairment and another two donors with LATE-NC did not have dementia. The mixed ADNC/LATE-NC group was older than the pure ADNC group, had a higher proportion of females compared to the pure ADNC and LATE-NC groups, and had more severe dementia versus the pure LATE-NC group. After adjustment for length of follow-up, cognitive and demographic factors, mixed ADNC/LATE-NC was associated with lower total Neuropsychiatric Inventory and agitation factor scores than pure ADNC, and lower frontal factor scores than pure LATE-NC. Our findings indicate that concomitant LATE pathology in Alzheimer's disease is not associated with greater neuropsychiatric symptom burden. Future longitudinal studies are needed to further investigate whether mixed ADNC/LATE-NC may be protective against agitation and frontal symptoms in dementia caused by Alzheimer's disease or LATE pathology.
Assuntos
Doença de Alzheimer/complicações , Encefalite Límbica/complicações , Transtornos Mentais/etiologia , Proteinopatias TDP-43/complicações , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Doença de Alzheimer/psicologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Estudos de Coortes , Proteínas de Ligação a DNA , Feminino , Humanos , Encefalite Límbica/psicologia , Estudos Longitudinais , Masculino , Transtornos Mentais/psicologia , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Caracteres Sexuais , Fatores Socioeconômicos , Proteinopatias TDP-43/psicologiaRESUMO
Brain tumors and paraneoplastic syndromes can cause various neuropsychiatric symptoms. Rarely, psychiatric symptoms may be the initial presentation of the underlying neurologic lesion. Brain imaging studies are crucial in the diagnosis of brain tumors. Paraneoplastic syndromes are mostly immune-mediated, and antineuronal antibodies may be detected in the blood or cerebrospinal fluid. Clinical suspicion is very important in assisting the diagnostic workup. Treatment of the psychiatric symptoms depends on the nature of the symptoms. Selection of the psychotropic agent has to be done carefully to minimize complications such as seizures and delirium secondary to anticholinergic toxicity. With advances in targeted therapies, immunology, and genetics, the future appears more promising.
Assuntos
Autoanticorpos/sangue , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/tratamento farmacológico , Síndromes Paraneoplásicas do Sistema Nervoso/sangue , Síndromes Paraneoplásicas do Sistema Nervoso/tratamento farmacológico , Humanos , Fatores Imunológicos/uso terapêutico , Encefalite Límbica/sangue , Encefalite Límbica/tratamento farmacológico , Encefalite Límbica/psicologia , Síndromes Paraneoplásicas do Sistema Nervoso/psicologia , Psicofarmacologia , Psicotrópicos/uso terapêuticoRESUMO
We report a case of anti-voltage-gated potassium channel (VGKC) limbic encephalitis in a 47-year-old man presenting with a 2-year history of psychiatric features. The patient had cognitive impairment, slurred speech, and a mildly unsteady gait but no other neurological deficits or seizures. Results of blood, urine, and cerebrospinal fluid tests and magnetic resonance imaging of the brain were normal. However, electroencephalography showed an epileptogenic focus in the bilateral temporal regions with mild to moderate diffuse encephalopathy. Autoimmune panel results confirmed the diagnosis of anti-VGKC limbic encephalitis, with a serum VGKC concentration of 6730 pmol/L. The patient was treated with Keppra and pulsed intravenous methylprednisolone for 3 days, and his behaviour improved.
Assuntos
Encefalite Límbica/psicologia , Autoanticorpos/sangue , Encéfalo/patologia , Encefalopatias/complicações , Disfunção Cognitiva/complicações , Eletroencefalografia , Humanos , Encefalite Límbica/complicações , Encefalite Límbica/imunologia , Encefalite Límbica/patologia , Masculino , Pessoa de Meia-Idade , Canais de Potássio de Abertura Dependente da Tensão da Membrana/sangue , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologiaRESUMO
Since the publication of Scoville and Milner's (1957) seminal paper, the precise functional role played by the hippocampus in support of human memory has been fiercely debated. For instance, the single question of whether the hippocampus plays a time-limited or an indelible role in the recollection of personal memories led to a deep and tenacious schism within the field. Similar polarizations arose between those who debated the precise nature of the role played by the hippocampus in support of semantic relative to episodic memories and in recall/recollection relative to familiarity-based recognition. At the epicenter of these divisions lies conflicting neuropsychological findings. These differences likely arise due to the consistent use of heterogeneous patient populations to adjudicate between these positions. Here we utilized traditional neuropsychological measures in a homogenous patient population with a highly discrete hippocampal lesion (i.e., VGKCC-Ab related autoimmune limbic encephalitis patients). We observed consistent impairment of recent episodic memories, a present but less striking impairment of remote episodic memories, preservation of personal semantic memory, and recall but not recognition memory deficits. We conclude that this increasingly well-characterized patient group may represent an important homogeneous population in which the functional role played by the hippocampus may be more precisely delineated.
Assuntos
Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/psicologia , Hipocampo/diagnóstico por imagem , Encefalite Límbica/diagnóstico por imagem , Encefalite Límbica/psicologia , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/psicologia , Testes Neuropsicológicos , Idoso , Doenças Autoimunes/complicações , Feminino , Humanos , Encefalite Límbica/complicações , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-IdadeRESUMO
Topographical disorientation (TD) in novel environments is considered to be a part of anterograde amnesia. A 56-year-old woman presented with pure TD only in novel environments following limbic encephalitis. She could not remember directions inside the hospital on weekly outpatient visits; however, her verbal and visual anterograde memories were normal. In the test of learning photographs of scenes, faces, and objects, only her scores for landscapes were worse than those in healthy controls. These findings suggested that her TD specific to landscapes and directions in novel environments was caused by category-specific memory impairment related to bilateral hippocampal and parahippocampal dysfunction.
Assuntos
Agnosia/psicologia , Amnésia Anterógrada/psicologia , Encefalite Límbica/psicologia , Agnosia/diagnóstico , Agnosia/etiologia , Amnésia Anterógrada/diagnóstico , Amnésia Anterógrada/etiologia , Feminino , Humanos , Encefalite Límbica/complicações , Encefalite Límbica/diagnóstico , Pessoa de Meia-Idade , Testes NeuropsicológicosRESUMO
OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale. METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38). RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p < 0.001), and had acceptable internal consistency (Cronbach α = 0.88). Additionally, in the validation cohort, the scale showed high interobserver reliability (ICC = 0.99) and internal consistency (Cronbach α = 0.92). INTERPRETATION: CASE is a novel clinical scale for AE with a high level of clinimetric properties. It would be suitable for application in clinical practice and might help overcome the limitations of current outcome scales for AE. ANN NEUROL 2019;85:352-358.
Assuntos
Doenças Autoimunes do Sistema Nervoso/fisiopatologia , Doenças Autoimunes do Sistema Nervoso/psicologia , Encefalite/fisiopatologia , Encefalite/psicologia , Adolescente , Adulto , Idoso , Agressão/psicologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/psicologia , Ataxia/etiologia , Ataxia/fisiopatologia , Doenças Autoimunes/complicações , Doenças Autoimunes/fisiopatologia , Doenças Autoimunes/psicologia , Doenças Autoimunes do Sistema Nervoso/complicações , Delusões/psicologia , Discinesias/etiologia , Discinesias/fisiopatologia , Distonia/etiologia , Distonia/fisiopatologia , Encefalite/complicações , Encefalomielite Aguda Disseminada/complicações , Encefalomielite Aguda Disseminada/fisiopatologia , Encefalomielite Aguda Disseminada/psicologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Transtornos Neurológicos da Marcha/fisiopatologia , Alucinações/psicologia , Humanos , Transtornos da Linguagem/etiologia , Transtornos da Linguagem/fisiopatologia , Encefalite Límbica/complicações , Encefalite Límbica/fisiopatologia , Encefalite Límbica/psicologia , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/fisiopatologia , Reprodutibilidade dos Testes , Convulsões/etiologia , Convulsões/fisiopatologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
RATIONALE: Limbic encephalitis is a parenchymal inflammation caused by viral, bacterial, or other microbial and postinfectious agents, which is usually expressed by multifocal neurological signs and cognitive impairment. PATIENT CONCERNS: A 50-year-old female was admitted in postacute phase, at our rehabilitative Center, to undertake neuro-motor treatment for a period of 4 months. DIAGNOSES: The patient was affected by limbic encephalitis. Clinical presentation revealed attention, memory and executive dysfunctions, as well as behavioral changes, emotional dysregulation and reduction of self-awareness. INTERVENTIONS: The patients received an intensive cognitive and motor rehabilitation training. OUTCOMES: Neuropsychological assessment and magnetic resonance imaging were performed before and after rehabilitative training to evaluate the cognitive and cerebral changes induced by treatment. The patient showed an improvement in cognitive performances and behavioral aspects. LESSONS: The reducing cognitive deficits, especially memory deficits, could improve quality of life by using available cognitive resources.
Assuntos
Disfunção Cognitiva/etiologia , Disfunção Cognitiva/reabilitação , Encefalite Límbica/psicologia , Encefalite Límbica/reabilitação , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/diagnóstico por imagem , Feminino , Humanos , Encefalite Límbica/diagnóstico por imagem , Pessoa de Meia-IdadeRESUMO
We report a case of a 51-year-old man with limbic encephalitis (LE) associated with antibodies against the α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic acid receptor (AMPAR). The patient presented with anterograde memory loss for 2 months. Cranial magnetic resonance and electroencephalogram were normal. AMPAR antibodies were found in blood serum and cerebrospinal fluid. All other test results were unremarkable. CT scans found a tumor in the right lobus superior pulmonis. A CT-guided needle biopsy was performed and pathological results showed small cell lung cancer (SCLC). The patient was diagnosed with LE associated with AMPAR antibodies and SCLC. Three months after immunotherapy and tumor removal, patient's memory was partially restored. We recommend that AMPAR antibodies should be detected in patients with classic LE with or without tumor. Prompt treatment of the tumor and immunotherapy are important.
Assuntos
Encefalite Límbica/imunologia , Receptores de AMPA/imunologia , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Eletroencefalografia , Humanos , Biópsia Guiada por Imagem , Imunoterapia , Encefalite Límbica/psicologia , Encefalite Límbica/terapia , Neoplasias Pulmonares/complicações , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/complicações , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: The aim was to report the clinical characteristics of 12 patients with limbic encephalitis (LE) who were antibody-negative after a comprehensive immunological study. METHODS: The clinical records of 163 patients with LE were reviewed. Immunohistochemistry on rat brain, cultured neurons and cell-based assays were used to identify neuronal autoantibodies. Patients were included if (i) there was adequate clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging information to classify the syndrome as LE, (ii) magnetic resonance images were accessible for central review and (iii) serum and CSF were available and were confirmed negative for neuronal antibodies. RESULTS: Twelve (7%) of 163 LE patients [median age 62 years; range 40-79; 9 (75%) male] without neuronal autoantibodies were identified. The most frequent initial complaints were deficits in short-term memory leading to hospital admission in a few weeks (median time 2 weeks; range 0.5-12). In four patients the short-term memory dysfunction remained as an isolated symptom during the entire course of the disease. Seizures, drowsiness and psychiatric problems were unusual. Four patients had solid tumors (one lung, one esophagus, two metastatic cervical adenopathies of unknown primary tumor) and one chronic lymphocytic leukemia. CSF showed pleocytosis in seven (58%) with a median of 13 white blood cells/mm3 (range 9-25). Immunotherapy included corticosteroids, intravenous immunoglobulins and combinations of both drugs or with rituximab. Clinical improvement occurred in six (54%) of 11 assessable patients. CONCLUSIONS: Despite the discovery of new antibodies, 7% of LE patients remain seronegative. Antibody-negative LE is more frequent in older males and usually develops with predominant or isolated short-term memory loss. Despite the absence of antibodies, patients may have an underlying cancer and respond to immunotherapy.
Assuntos
Autoanticorpos/análise , Encefalite Límbica/imunologia , Encefalite Límbica/terapia , Adulto , Idoso , Animais , Autoantígenos/imunologia , Células Cultivadas , Feminino , Humanos , Imuno-Histoquímica , Imunoterapia , Leucócitos/imunologia , Leucocitose , Encefalite Límbica/psicologia , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Memória de Curto Prazo , Pessoa de Meia-Idade , Neoplasias/complicações , Neurônios/imunologia , Ratos , Resultado do TratamentoRESUMO
Autoimmune encephalitis is rare. Several auto- antibodies are described in autoimmune encephalitis. We describe a case of autoimmune limbic encephalitis associated with positive voltage gated potassium channel (VGKC) antibodies and positive leucine-rich glioma inactivated protein 1 antibodies (LGI1). A 33-year-old Saudi housewife, she presented with 2 months history of cognitive deterioration and recurrent left facio-brachial dystonic seizures followed by generalized tonic clonic seizures. At times the seizures are preceded by rising epigastric aura and shortness of breath. The neurological examination was normal apart from upgoing left plantar reflex. She had borderline IQ of 76 with impaired verbal fluency and impaired visual and verbal memory. Magnetic resonance imaging of the brain showed right mesial temporal non-enhancing lesion. Cerebrospinal fluid examination was positive for LGI1 and VGKC. Optimal seizure control was achieved with immunotherapy.
Assuntos
Doenças Autoimunes , Encefalite Límbica , Adulto , Autoanticorpos/metabolismo , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/fisiopatologia , Doenças Autoimunes/psicologia , Eletroencefalografia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Encefalite Límbica/diagnóstico por imagem , Encefalite Límbica/fisiopatologia , Encefalite Límbica/psicologia , Imageamento por Ressonância Magnética , Proteínas de Membrana/sangue , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/sangue , Proteínas do Tecido Nervoso/imunologia , Proteínas/imunologia , Tomógrafos ComputadorizadosRESUMO
OBJECTIVE: To report 10 patients with limbic encephalitis (LE) and adenylate kinase 5 autoantibodies (AK5-Abs). METHODS: We conducted a retrospective study in a cohort of 50 patients with LE with uncharacterized autoantibodies and identified a specific target using immunohistochemistry, Western blotting, immunoprecipitation, mass spectrometry, and cell-based assay. RESULTS: AK5 (a known autoantigen of LE) was identified as the target of antibodies in the CSFs and sera of 10 patients with LE (median age 64 years; range 57-80), which was characterized by subacute anterograde amnesia without seizure and sometimes preceded by a prodromal phase of asthenia or mood disturbances. Anterograde amnesia can be isolated, but some patients also complained of prosopagnosia, paroxysmal anxiety, or abnormal behavior. No associated cancer was observed. All 10 patients had bilateral hippocampal hypersignal on a brain MRI. CSF analysis generally showed a mild pleiocytosis with elevated immunoglobulin G index and oligoclonal bands, as well as high levels of tau protein with normal concentration of Aß42 and phospho-tau, suggesting a process of neuronal death. Except for one patient, clinical response to immunotherapy was unfavorable, with persistence of severe anterograde amnesia. Two patients evolved to severe cognitive decline. Hippocampal atrophy was observed on control brain MRI. Using in vitro tests on hippocampal neurons, we did not identify clues suggesting a direct pathogenic role of AK5-Abs. CONCLUSIONS: AK5-Abs should be systematically considered in aged patients with subacute anterograde amnesia. Recognition of this disorder is important to develop new treatment strategies to prevent irreversible limbic damage.
Assuntos
Adenilato Quinase/imunologia , Autoanticorpos/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Encefalite Límbica/diagnóstico , Encefalite Límbica/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Encéfalo/patologia , Diagnóstico Diferencial , Feminino , Células HEK293 , Humanos , Imunoterapia , Encefalite Límbica/psicologia , Encefalite Límbica/terapia , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
There is currently much debate about whether the precise role of the hippocampus in scene processing is predominantly constructive, perceptual, or mnemonic. Here, we developed a novel experimental paradigm designed to control for general perceptual and mnemonic demands, thus enabling us to specifically vary the requirement for constructive processing. We tested the ability of patients with selective bilateral hippocampal damage and matched control participants to detect either semantic (e.g., an elephant with butterflies for ears) or constructive (e.g., an endless staircase) violations in realistic images of scenes. Thus, scenes could be semantically or constructively 'possible' or 'impossible'. Importantly, general perceptual and memory requirements were similar for both types of scene. We found that the patients performed comparably to control participants when deciding whether scenes were semantically possible or impossible, but were selectively impaired at judging if scenes were constructively possible or impossible. Post-task debriefing indicated that control participants constructed flexible mental representations of the scenes in order to make constructive judgements, whereas the patients were more constrained and typically focused on specific fragments of the scenes, with little indication of having constructed internal scene models. These results suggest that one contribution the hippocampus makes to scene processing is to construct internal representations of spatially coherent scenes, which may be vital for modelling the world during both perception and memory recall. © 2016 The Authors. Hippocampus Published by Wiley Periodicals, Inc.
Assuntos
Hipocampo/lesões , Hipocampo/fisiopatologia , Julgamento/fisiologia , Semântica , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Adulto , Idoso , Compreensão/fisiologia , Discriminação Psicológica/fisiologia , Hipocampo/diagnóstico por imagem , Humanos , Encefalite Límbica/complicações , Encefalite Límbica/diagnóstico por imagem , Encefalite Límbica/fisiopatologia , Encefalite Límbica/psicologia , Masculino , Transtornos da Memória/diagnóstico por imagem , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tempo de Reação , Método Simples-Cego , Lobo Temporal/diagnóstico por imagem , Lobo Temporal/fisiopatologiaRESUMO
OBJECTIVE: To illustrate the neuropsychiatric and imaging findings in a confirmed case of voltage-gated potassium channel antibody limbic encephalitis. METHOD: Case report and review of the literature. RESULTS: A 64-year-old man presented with several months' history of obsessive thoughts and compulsions associated with faciobrachial dystonic seizures. He had no significant past medical and psychiatric history. Physical examinations revealed only mildly increased tone in the left upper limb. Bedside cognitive testing was normal. Positron-emission tomography showed intense symmetrical uptake in the corpus striatum. No underlying malignancy was identified on whole body imaging. Magnetic resonance imaging, lumbar puncture and electroencephalogram were normal. Serum voltage-gated potassium channel antibodies were strongly positive. The patient had a favourable response to antiepileptic drugs, oral steroids and immunotherapy. CONCLUSIONS: Voltage-gated potassium channel limbic encephalitis characteristically presents with neuropsychiatric symptoms and temporal lobe seizures. Positron-emission tomography-computed tomography can be a useful adjunct to the clinical and biochemical work-up.
Assuntos
Anticorpos/sangue , Encefalite Límbica/diagnóstico por imagem , Encefalite Límbica/psicologia , Convulsões/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Humanos , Imunoterapia , Encefalite Límbica/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Esteroides/uso terapêuticoRESUMO
OBJECTIVE: This nationwide study gives a detailed description of the clinical features and long-term outcome of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis. METHODS: We collected patients prospectively from October 2013, and retrospectively from samples sent to our laboratory from January 2007. LGI1 antibodies were confirmed with both cell-based assay and immunohistochemistry. Clinical information was obtained in interviews with patients and their relatives and from medical records. Initial MRI and follow-up MRI were revised blindly. Neuropsychological assessment was performed in those patients with follow-up over 2 years. RESULTS: Annual incidence in the Netherlands was 0.83/million. A total of 34/38 patients had a limbic encephalitis. Subtle focal seizures (66%, autonomic or dyscognitive) and faciobrachial dystonic seizures (FBDS, 47%) mostly occurred before onset of memory disturbance. Later in the disease course, 63% had tonic-clonic seizures. Initial MRI showed hippocampal T2 hyperintensity in 74% of the patients. These lesions evolved regularly into mesial temporal sclerosis (44%). Substantial response to immunotherapy was seen in 80%, with early response of seizures and slow recovery of cognition. At follow-up ≥2 years, most surviving patients reported mild residual cognitive deficit with spatial disorientation. A total of 86% had persistent amnesia for the disease period. Relapses were common (35%) and presented up to 8 years after initial disease. Two-year case fatality rate was 19%. CONCLUSIONS: Anti-LGI1 encephalitis is a homogenous clinical syndrome, showing early FBDS and other focal seizures with subtle clinical manifestations, followed by memory disturbances. Better recognition will lead to earlier diagnosis, essential for prompt start of treatment. Long-term outcome of surviving patients is mostly favorable, but relapses are common.
Assuntos
Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Encefalite Límbica/epidemiologia , Encefalite Límbica/imunologia , Proteínas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Doenças Autoimunes/psicologia , Doenças Autoimunes/terapia , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Incidência , Peptídeos e Proteínas de Sinalização Intracelular , Encefalite Límbica/psicologia , Encefalite Límbica/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Síndrome , Fatores de TempoRESUMO
OBJECTIVE: To determine efficacy and safety of rituximab treatment as a second-line immunotherapy treatment for autoimmune limbic encephalitis (ALE) and to determine factors associated with functional improvement and favorable outcome following rituximab treatment. METHODS: We recruited 80 patients with ALE who were treated with rituximab as a second-line immunotherapy from the Korea Autoimmune Synaptic and Paraneoplastic Encephalitis Registry and reviewed 81 patients without rituximab as a control. We grouped patients according to the detection or type of antibodies; in addition, we evaluated clinical, laboratory, first-line immunotherapy, and rituximab treatment profiles and defined main outcomes as improvements on the modified Rankin Scale (mRS) score and a favorable mRS score (0-2) at the last follow-up. RESULTS: Functional improvement occurred more frequently in the rituximab group compared to the control group. In the rituximab group, 30 (37.5%) patients had synaptic autoantibodies, 15 (18.8%) in the paraneoplastic autoantibodies, and 35 (43.8%) were antibody-negative. The effect of rituximab was the same regardless of autoantibody status. Additional monthly rituximab therapy and partial response to first-line immunotherapies were associated with mRS score improvements, as well as favorable mRS scores. mRS scores of 4-6 as the worst neurologic status predicted an unfavorable mRS score. There were no reported serious infusion-related or infectious adverse effects of rituximab. CONCLUSIONS: Rituximab is effective and safe as a second-line immunotherapy for ALE, regardless of autoantibody status. Additional monthly rituximab therapy might potentiate the efficacy of rituximab. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that rituximab improves mRS scores for patients with autoimmune limbic encephalitis who fail first-line therapy.