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4.
Ned Tijdschr Geneeskd ; 1682024 08 20.
Artigo em Holandês | MEDLINE | ID: mdl-39228334

RESUMO

BACKGROUND: Cognitive disorders usually develop slowly over years and are mainly caused by untreatable neurodegenerative disorders. Rapidly progressive cognitive disorders should raise suspicion of an underlying and treatable psychiatric, internal or neurological condition. Timely recognition of these conditions is important. CASE: We present the case of a 68-year old man, presenting on the emergency department with a history of progressive cognitive impairment since several weeks. Cerebral MRI showed T2-hyperintensities in the left hippocampal, mesotemporal and insular regions; lesser so in the right mesotemporal region. After initial treatment for herpesencephalitis and autoimmune encephalitis, we diagnosed neurolues and started treatment with benzylpenicillin. CONCLUSION: It may be difficult to diagnose neurolues because the vast variety of clinical symptoms and radiological signs. This case shows that neurolues should be considered in a patient with rapidly progressive cognitive disorders and that neurolues can mimic a herpesencephalitis or an autoimmune encephalitis. Timely recognition is important to prevent irreversible damage.


Assuntos
Transtornos Cognitivos , Humanos , Idoso , Masculino , Diagnóstico Diferencial , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Imageamento por Ressonância Magnética , Encefalite por Herpes Simples/diagnóstico , Encefalite por Herpes Simples/complicações , Encefalite por Herpes Simples/tratamento farmacológico , Encefalite/diagnóstico , Encefalite/complicações
7.
Clin Neurol Neurosurg ; 245: 108519, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39216416

RESUMO

Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by the destruction of thyroid follicular cells by thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), leading to hypothyroidism. Hashimoto's encephalopathy (HE) is associated with elevated levels of antithyroid antibodies. An important question is whether brain alterations precede the development of HE and are present in euthyroid patients with HT, and what pathomechanisms could be responsible for these changes. A PubMed search was conducted to identify studies addressing this issue. Numerous questionnaire studies confirmed impairments in cognitive functioning, mental and physical health, and overall well-being in euthyroid HT patients. Additionally, some imaging and mouse model studies indicate that euthyroid patients with HT likely have central nervous system alterations. Antibodies may be involved in the development of these changes. Some research suggests the role of TPOAb and TgAb, while other studies highlight the involvement of coexisting antibodies. Determining whether antibodies are assessed in serum or cerebrospinal fluid (CSF) is crucial. Antibody-specific indices (ASIs) can differentiate between antibodies passively diffusing from the serum and brain-derived antibodies, and could serve as biomarkers for brain alterations in HT patients. Much more research is needed to identify reliable biomarkers and treatments that could improve the quality of life for these patients.


Assuntos
Autoanticorpos , Doença de Hashimoto , Humanos , Doença de Hashimoto/complicações , Doença de Hashimoto/imunologia , Autoanticorpos/sangue , Encefalite/imunologia , Encefalopatias/imunologia , Animais , Tireoglobulina/imunologia , Iodeto Peroxidase/imunologia
8.
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
9.
Korean J Radiol ; 25(9): 807-823, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39197826

RESUMO

Autoimmune encephalitis (AE) is a category of immune-mediated disorders of the central nervous system (CNS) affecting children and adults. It is characterized by the subacute onset of altered mentation, neurocognitive issues, refractory seizures/drug-resistant epilepsy, movement disorders, and/or autonomic dysfunction. AE is mediated by autoantibodies targeting specific surface components or intracytoplasmic antigens in the CNS, leading to functional or structural alterations. Multiple triggers that induce autoimmunity have been described, which are mainly parainfectious and paraneoplastic. The imaging features of AE often overlap with each other and with other common causes of encephalitis/encephalopathy (infections and toxic-metabolic etiologies). Limbic encephalitis is the most common imaging finding shared by most of these entities. Cortical, basal ganglia, diencephalon, and brainstem involvement may also be present. Cerebellar involvement is rare and is often a part of paraneoplastic degeneration. Owing to an improved understanding of AE, their incidence and detection have increased. Hence, in an appropriate setting, a high degree of suspicion is crucial when reporting clinical MRIs to ensure prompt treatment and better patient outcomes. In this review, we discuss the pathophysiology of AE and common etiologies encountered in clinical practice.


Assuntos
Encefalite , Imageamento por Ressonância Magnética , Humanos , Encefalite/imunologia , Encefalite/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Doença de Hashimoto/imunologia , Doença de Hashimoto/diagnóstico por imagem , Autoanticorpos/imunologia
10.
Neurology ; 103(6): e209682, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39190859

RESUMO

BACKGROUND AND OBJECTIVES: The 2023 criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) perform well in adults but have not been assessed in children. METHODS: This prospective observational nationwide study includes children and adults with demyelinating syndromes or encephalitis, whose serum or CSF was found MOG-immunoglobulin G (IgG) positive at Institut d'Investigacions Biomèdiques August Pi i Sunyer-Hospital Clínic of Barcelona (Spain). Exclusion criteria were lack of clinical information and follow-up <1 year, and serum unavailable for antibody testing. The primary outcome was to assess the accuracy of the 2023 MOGAD criteria, using as gold standard the most plausible diagnosis after a follow-up >1 year. MOGAD criteria were retrospectively applied assessing core syndromes, supportive clinical-radiological features, and MOG-IgG titers. Patients tested ≤3 months of a disease attack (acute phase) or afterward (remission) were considered separately. The positive predictive value (PPV) of the criteria (true-positive [patients classified as MOGAD and MOGAD diagnosis last follow-up] divided by total positive [all patients classified as MOGAD]), and its 95% CI, was calculated with the Wilson procedure. RESULTS: A total of 257 patients (133 children) were included in the study (median age 15 years [interquartile range 6-38], 54% female). Among 202 patients assessed during a disease attack, 158 (78%) had high MOG-IgG serum titers, 36 (18%) low titers, and 8 (4%) antibodies only in CSF. No differences were identified between patients with high and low titers, but those with low titers were more likely to have an alternative diagnosis at last follow-up (2/36 [6%] vs 0/158, p = 0.012). Supportive features were present in 230 of 257 (89%) patients, regardless of age, MOG-IgG titers, and core syndromes except for optic neuritis in adults whose assessment with orbital MRI was not systematic. Overall, 240 of 257 (94%) patients were well classified by the MOGAD criteria (e.g., 236 eventually having MOGAD and 4 alternative diagnoses), and 17 were wrongly classified (e.g., 11 eventually having MOGAD and 6 alternative diagnoses). Although the criteria classified better during disease attacks than during remissions (187 [96%] vs 49 [89%] serum MOG-IgG-positive patients were well-classified, p = 0.038), the PPV was high in both settings (99% [95% CI 97-100] vs 98% [95% CI 89-100]). DISCUSSION: The 2023 MOGAD criteria correctly identified most children and adults with MOGAD. The highest accuracy occurred when they were applied during disease attacks. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the 2023 MOGAD criteria accurately identify adults and children with MOGAD.


Assuntos
Autoanticorpos , Glicoproteína Mielina-Oligodendrócito , Humanos , Glicoproteína Mielina-Oligodendrócito/imunologia , Criança , Masculino , Feminino , Adulto , Adolescente , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Adulto Jovem , Estudos Prospectivos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Pré-Escolar , Espanha , Pessoa de Meia-Idade , Encefalite/imunologia , Encefalite/diagnóstico , Encefalite/sangue , Estudos Retrospectivos
11.
Biosens Bioelectron ; 264: 116664, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39159588

RESUMO

Implantable devices for brain-machine interfaces and managing neurological disorders have experienced rapid growth in recent years. Although functional implants offer significant benefits, issues related to transient trauma and long-term biocompatibility and safety are of significant concern. Acute inflammatory reaction in the brain tissue caused by microimplants is known to be an issue but remains poorly studied. This study presents the use of titanium oxynitride (TiNO) nanofilm with defined surface plasmon resonance (SPR) properties for point-of-care characterizing of acute inflammatory responses during robot-controlled micro-neuro-implantation. By leveraging surface-enriched oxynitride, TiNO nanofilms can be biomolecular-functionalized through silanization. This label-free TiNO-SPR biosensor exhibits a high sensitivity toward the inflammatory cytokine interleukin-6 with a detection limit down to 6.3 fg ml-1 and a short assay time of 25 min. Additionally, intraoperative monitoring of acute inflammatory responses during microelectrode implantation in the mice brain has been accomplished using the TiNO-SPR biosensors. Through intraoperative cerebrospinal fluid sampling and point-of-care plasmonic biosensing, the rhythm of acute inflammatory responses induced by the robot-controlled brain microelectrodes implantation has been successfully depicted, offering insights into intraoperative safety assessment of invasive brain-machine interfaces.


Assuntos
Ressonância de Plasmônio de Superfície , Titânio , Animais , Titânio/química , Camundongos , Técnicas Biossensoriais , Encefalite/etiologia , Microeletrodos , Interleucina-6/análise , Interleucina-6/líquido cefalorraquidiano , Encéfalo , Interfaces Cérebro-Computador , Desenho de Equipamento , Eletrodos Implantados/efeitos adversos , Humanos
12.
Ital J Pediatr ; 50(1): 158, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39183357

RESUMO

BACKGROUND: Contactin-associated protein-2(CASPR2) antibody-associated autoimmune encephalitis(AE) is rare in children. This study aimed to report the clinical characteristics and long-term outcome of CASPR2 autoimmunity in children to expand the disease spectrum. METHODS: Children who were hospitalized in our hospital with clinically suspected AE from May 2015 to April 2022 and underwent neuronal surface antibodies detections were retrospectively analyzed. Clinical data of patients with CASPR2 autoimmunity were collected. RESULTS: Patients who were positive for NMDAR-IgG, CASPR2-IgG, LGI1-IgG and IgLON5-IgG occupied 95.2%(119/125),3.2%(4/125),0.8%(1/125) and 0.8%(1/125), respectively.The median onset age of the 4 patients with CASPR2-IgG was 5.6 years. The most common symptoms were psychiatric symptoms/abnormal behavior(3/4) and sleep dysfunction(3/4). One patient developed a phenotype of Rasmussen encephalitis(RE). Tumor was absent in our patients. Two patients showed abnormal findings on initial brain magnetic resonance imaging(MRI) scans. All the patients showed favorable response to immunotherapy except the patient with RE experienced recurrent symptoms who finally achieved remission after surgery. All the patients had a favorable long-term outcome at the last follow-up(33-58months). CONCLUSIONS: CASPR2 autoimmunity may be the second most common anti-neuronal surface antibodies associated neurological disease in children. Psychiatric symptoms/abnormal behavior and sleep disorder were common in children with CASPR2-associated AE. Tumor was rare in those patients. Most pediatric patients had a favorable long-term outcome.


Assuntos
Autoanticorpos , Encefalite , Proteínas de Membrana , Proteínas do Tecido Nervoso , Humanos , Masculino , Feminino , Criança , Encefalite/imunologia , Encefalite/diagnóstico , Estudos Retrospectivos , Proteínas do Tecido Nervoso/imunologia , Proteínas de Membrana/imunologia , Pré-Escolar , Doença de Hashimoto/imunologia , Doença de Hashimoto/diagnóstico , Adolescente
13.
Int J Mol Sci ; 25(15)2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39126055

RESUMO

Rasmussen's encephalitis (RE) stands as a rare neurological disorder marked by progressive cerebral hemiatrophy and epilepsy resistant to medical treatment. Despite extensive study, the primary cause of RE remains elusive, while its histopathological features encompass cortical inflammation, neuronal degeneration, and gliosis. The underlying molecular mechanisms driving disease progression remain largely unexplored. In this case study, we present a patient with RE who underwent hemispherotomy and has remained seizure-free for over six months, experiencing gradual motor improvement. Furthermore, we conducted molecular analysis on the excised brain tissue, unveiling a decrease in the expression of cell-cycle-associated genes coupled with elevated levels of BDNF and TNF-α proteins. These findings suggest the potential involvement of cell cycle regulators in the progression of RE.


Assuntos
Encefalite , Humanos , Encefalite/genética , Encefalite/patologia , Encefalite/metabolismo , Masculino , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Encéfalo/patologia , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Cerebral/patologia , Córtex Cerebral/metabolismo , Feminino , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Ciclo Celular/genética
14.
Neurol India ; 72(4): 877-880, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39216051

RESUMO

Super refractory status epilepticus (SRSE) is a condition associated with high rates of mortality and morbidity. We report the treatment protocol of magnesium sulphate infusion adapted for the management of a case of super refractory status epilepticus that lasted for 4 weeks. A young lady presented in altered sensorium with a history of fever followed by uncontrolled seizures of 2 weeks duration. Her serum tested weakly positive for GABA-B receptor antibody. Her seizures were not controlled despite being on multiple antiepileptics and anesthetic induction. Intravenous magnesium infusion was initiated and serum magnesium was titrated up to a final target concentration of 3.8-6.5 mg/dl. Seizure control was achieved after 11 days of the infusion. This case is the longest reported successful use of magnesium sulfate infusion for control of super refractory status epileptics.


Assuntos
Encefalite , Sulfato de Magnésio , Estado Epiléptico , Humanos , Estado Epiléptico/tratamento farmacológico , Sulfato de Magnésio/administração & dosagem , Feminino , Encefalite/tratamento farmacológico , Adulto , Anticonvulsivantes/administração & dosagem , Doença de Hashimoto/tratamento farmacológico , Doença de Hashimoto/complicações , Receptores de GABA-B/imunologia , Infusões Intravenosas , Autoanticorpos/sangue
15.
Brain Behav Immun ; 121: 303-316, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39098438

RESUMO

BACKGROUND: Cerebral Palsy (CP) is a major cause of motor and cognitive disability in children due to injury to the developing brain. Early intensive sensorimotor rehabilitation has been shown to change brain structure and reduce CP symptoms severity. We combined environmental enrichment (EE) and treadmill training (TT) to observe the effects of a one-week program of sensorimotor stimulation (EETT) in animals exposed to a CP model and explored possible mechanisms involved in the functional recovery. METHODS: Pregnant Wistar rats were injected with Lipopolysaccharide (LPS - 200 µg/kg) intraperitoneally at embryonic days 18 and 19. At P0, pups of both sexes were exposed to 20' anoxia at 37 °C. From P2 to P21, hindlimbs were restricted for 16 h/day during the dark cycle. EETT lasted from P21 to P27. TT - 15 min/day at 7 cm/s. EE - 7 days in enriched cages with sensorimotor stimulus. Functional 3D kinematic gait analysis and locomotion were analyzed. At P28, brains were collected for ex-vivo MRI and histological assessment. Neurotrophins and key proteins involved in CNS function were assessed by western blotting. RESULTS: CP model caused gross and skilled locomotor disruption and altered CNS neurochemistry. EETT reversed locomotor dysfunction with minor effects over gait kinematics. EETT also decreased brain inflammation and glial activation, preserved myelination, upregulated BDNF signaling and modulated the expression of proteins involved in excitatory synaptic function in the brain and spinal cord. CONCLUSIONS: Using this translational approach based on intensive sensorimotor rehabilitation, we highlight pathways engaged in the early developmental processes improving neurological recovery observed in CP.


Assuntos
Paralisia Cerebral , Modelos Animais de Doenças , Locomoção , Plasticidade Neuronal , Ratos Wistar , Animais , Paralisia Cerebral/reabilitação , Paralisia Cerebral/fisiopatologia , Plasticidade Neuronal/fisiologia , Ratos , Feminino , Locomoção/fisiologia , Masculino , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Gravidez , Recuperação de Função Fisiológica/fisiologia , Encefalite/metabolismo , Encefalite/fisiopatologia , Encefalite/reabilitação , Marcha/fisiologia , Condicionamento Físico Animal/fisiologia , Condicionamento Físico Animal/métodos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/fisiopatologia
16.
J Comp Pathol ; 213: 73-77, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39146622

RESUMO

A 10-year-old spayed mixed breed dog presented with severe neurological signs. Computed tomography revealed a cranial mediastinal mass, osteolysis of the right second rib and second thoracic vertebra, tracheobronchial and mesenteric lymph node enlargement, pneumonia and pleural effusion. Magnetic resonance imaging detected lesions in the white matter of the right frontal lobe and left cerebral hemisphere with contrast-enhanced T1-weighted images showing demarcated enhancement. On cut section, the surface of the right cerebral frontal lobe and left cerebral hemisphere corticomedullary junctions were indistinct and the white matter was discoloured. Microscopically, multicentric granulomatous inflammation was seen in the brain, cranial mediastinal mass, masses on the right second rib, tracheobronchial and mesenteric lymph nodes, heart, kidneys, lungs and oesophagus. Necrosis and hyaline fungal structures were frequently observed in the centre of the granulomas. These fungi had septae, Y-shaped branching and were 2-3 µm in width. Sequence analysis of DNA from formalin-fixed paraffin-embedded samples identified the fungi as Schizophyllum commune. Based on these findings, this case was diagnosed as disseminated S. commune infection. This is the first report of granulomatous encephalitis caused by S. commune in a dog.


Assuntos
Doenças do Cão , Encefalite , Schizophyllum , Animais , Cães , Doenças do Cão/microbiologia , Doenças do Cão/patologia , Encefalite/veterinária , Granuloma/veterinária , Feminino , Micoses/veterinária
17.
Arq Neuropsiquiatr ; 82(7): 1-15, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39089672

RESUMO

BACKGROUND: Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis. OBJECTIVE: With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method. METHODS: A total of 25 panelists, including adult and child neurologists, participated in the study. RESULTS: The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSION: The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system.


ANTECEDENTES: Encefalites autoimunes (EAIs) são um grupo de doenças inflamatórias caracterizadas pela presença de anticorpos contra antígenos neuronais e gliais, que ocasionam sintomas psiquiátricos subagudos, queixas de memória e distúrbios anormais do movimento. A maioria dos pacientes é jovem, e o atraso no tratamento está associado a pior prognóstico. OBJETIVO: Com o apoio da Academia Brasileira de Neurologia (ABN) e da Sociedade Brasileira de Neurologia Infantil (SBNI), desenvolvemos um consenso sobre o diagnóstico e o tratamento da EAIs no Brasil utilizando a metodologia Delphi. MéTODOS: Um total de 25 especialistas, incluindo neurologistas e neurologistas infantis, foram convidados a participar. RESULTADOS: Os especialistas concordaram que os pacientes com critérios de possíveis EAIs devem ser submetidos ao rastreio de anticorpos antineuronais no soro e no líquido cefalorraquidiano (LCR) por meio das técnicas de ensaio baseado em tecidos (tissue-based assay, TBA, em inglês) e ensaio baseado em células (cell-based assay, CBA, em inglês). As crianças também devem ser submetidas ao rastreio de de anticorpo contra a glicoproteína da mielina de oligodendrócitos (anti-myelin oligodendrocyte glycoprotein, anti-MOG, em inglês). O tratamento deve ser iniciado dentro das primeiras 4 semanas dos sintomas, sendo as opções de primeira linha metilprednisolona combinada com imunoglobulina intravenosa (IGIV) ou plasmaférese. O tratamento de segunda linha inclui rituximabe e ciclofosfamida. Bortezomib e tocilizumab são opções de tratamento de terceira linha. A maioria das crises epilépticas nas EAIs são sintomáticas, e os fármacos anticrise podem ser desmamadas após a fase aguda. Em relação à encefalite antirreceptor de N-metil-D-aspartato (anti-N-methyl-D-aspartate receptor, anti-NMDAR, em inglês), os especialistas concordaram que agentes imunossupressores orais não devem ser usados. Os pacientes devem ser avaliados na fase aguda e pós-aguda mediante escalas funcionais e cognitivas, como Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Modified Rankin Scale (mRS), e Clinical Assessment Scale in Autoimmune Encephalitis (CASE). CONCLUSãO: Esta pesquisa oferece evidências tangíveis do manejo efetivo de pacientes com EAIs no sistema de saúde Brasileiro.


Assuntos
Consenso , Encefalite , Humanos , Encefalite/diagnóstico , Encefalite/terapia , Encefalite/imunologia , Brasil , Criança , Adulto , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/terapia , Técnica Delphi , Autoanticorpos/sangue
18.
Brain Behav Immun ; 122: 266-278, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39142424

RESUMO

Anti-contactin associated protein receptor 2 (CASPR2) encephalitis is a severe autoimmune encephalitis with a variable clinical phenotype including behavioral abnormalities, cognitive decline, epileptic seizures, peripheral nerve hyperexcitability and neuropathic pain. The detailed mechanisms of how CASPR2 autoantibodies lead to synaptic dysfunction and clinical symptoms are largely unknown. Aiming for analyses from the molecular to the clinical level, we isolated antibody-secreting cells from the cerebrospinal fluid of two patients with CASPR2 encephalitis. From these we cloned four anti-CASPR2 human monoclonal autoantibodies (mAbs) with strong binding to brain and peripheral nerves. All were highly hypermutated and mainly of the IgG4 subclass. Mutagenesis studies determined selective binding to the discoidin domain of CASPR2. Surface plasmon resonance revealed affinities with dissociation constants KD in the pico- to nanomolar range. CASPR2 mAbs interrupted the interaction of CASPR2 with its binding partner contactin 2 in vitro and were internalized after binding to CASPR2-expressing cells. Electrophysiological recordings of rat hippocampal slices after stereotactic injection of CASPR2 mAbs showed characteristic afterpotentials following electrical stimulation. In vivo experiments with intracerebroventricular administration of human CASPR2 mAbs into mice and rats showed EEG-recorded brain hyperexcitability but no spontaneous recurrent seizures. Behavioral assessment of infused mice showed a subtle clinical phenotype, mainly affecting sociability. Mouse brain MRI exhibited markedly reduced resting-state functional connectivity without short-term structural changes. Together, the experimental data support the direct pathogenicity of CASPR2 autoantibodies. The minimally invasive EEG and MRI techniques applied here may serve as novel objective, quantifiable tools for improved animal models, in particular for subtle neuropsychiatric phenotypes or repeated measurements.


Assuntos
Anticorpos Monoclonais , Autoanticorpos , Encefalite , Imageamento por Ressonância Magnética , Proteínas de Membrana , Proteínas do Tecido Nervoso , Animais , Autoanticorpos/imunologia , Autoanticorpos/metabolismo , Ratos , Humanos , Camundongos , Imageamento por Ressonância Magnética/métodos , Proteínas do Tecido Nervoso/imunologia , Proteínas do Tecido Nervoso/metabolismo , Masculino , Encefalite/imunologia , Encefalite/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Membrana/imunologia , Modelos Animais de Doenças , Feminino , Encéfalo/metabolismo , Hipocampo/metabolismo , Comportamento Animal/fisiologia
19.
Epilepsy Res ; 206: 107439, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39197377

RESUMO

INTRODUCTION: Seizures and epilepsy are well-documented in association with autoimmune encephalitis. Despite this, a notable gap exists in understanding the persistence of seizures beyond the acute phase, particularly within the context of low- and low-middle-income settings. OBJECTIVE: To evaluate the frequency, clinical characteristics, diagnosis, and potential factors associated with the occurrence and persistence of seizures in autoimmune encephalitis patients. METHODS: This was a retrospective, cross-sectional study. Patients diagnosed with possible, probable or confirmed autoimmune encephalitis according to the Graus criteria at the "Instituto Nacional de Ciencias Neurológicas" in Lima, Peru, were included between January 2018 and April 2023. Demographic, clinical, diagnosis, and management information was recorded. A bivariate analysis was performed considering the persistence of seizures at one-year follow-up and a second analysis was performed to compare the groups according to the anti N-methyl-D-aspartate receptor (NMDAR) antibody results. RESULTS: Sixty patients predominantly male (40; 66.7 %) were included. Only 36 (60 %) patients were tested for antibodies, 16 (44.4 %) were NMDAR positive. 46 (76.7 %) patients had at least one seizure and 13 (37.1 %) had seizures after 1 year of follow-up. Patients with seizure relapse were younger, 20 (IQR: 18-28) versus 29.5 years (IQR: 21-48), p=0.049. Four (44.4 %) patients with persistent seizures had positive NMDAR results. Similar sex distributions, no differences in seizure characteristics, and higher CSF cell count in the NMDAR-positive group were observed. Neuroimaging, EEG findings, and follow-up times were comparable between the groups. CONCLUSIONS: We found a 37.1 % seizures rate after one year of follow-up, predominantly in younger patients.


Assuntos
Encefalite , Convulsões , Humanos , Masculino , Feminino , Estudos Retrospectivos , Estudos Transversais , Adulto , Encefalite/epidemiologia , Encefalite/complicações , Encefalite/diagnóstico , Peru/epidemiologia , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Doença de Hashimoto/epidemiologia , Autoanticorpos/sangue
20.
Medicine (Baltimore) ; 103(33): e39146, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39151524

RESUMO

RATIONALE: Anti-Myelin oligodendrocyte glycoprotein (MOG) and anti-metabotropic glutamate receptor 5 (mGluR5) double antibody positive encephalitis characterized by optic neuritis is extremely rare. We present a case of overlapping syndrome of MOG-IgG-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis. PATIENT CONCERNS: A 60-year-old Chinses woman presented to the hospital with progressive vision loss and headache for 1 week. The cerebrospinal fluid examination was within the normal range. Visual evoked potentials study disclosed prolonged latency of P100 bilaterally. Fundus examination revealed indistinct boundaries of both optic discs. Her brain magnetic resonance imaging showed patchy hyperintensity in the posterior horn of the left ventricle and the left optic nerve. Her serum was positive for anti-MOG and anti-mGluR5 antibodies. DIAGNOSIS: The patient was diagnosed with overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis mainly based on the clinical symptoms and further test of the antibody in serum. INTERVENTIONS AND OUTCOMES: She was subsequently subjected to empirical treatment with intravenous methylprednisolone. After discharge, she was given a tapering dose of oral prednisone, alongside mycophenolate mofetil. On outpatient follow-up, her symptoms showed no relapse after 1 month, and her condition remained stable. LESSONS: Early recognition of autoimmune encephalitis is crucial. The detection of cerebrospinal fluid and serum of autoimmune encephalitis and demyelinating diseases of the CNS, including MOG-IgG and mGluR5-IgG, should be strengthened in order to make a precise diagnosis and develop a comprehensive treatment plan in a timely manner.


Assuntos
Autoanticorpos , Glicoproteína Mielina-Oligodendrócito , Neurite Óptica , Receptor de Glutamato Metabotrópico 5 , Humanos , Feminino , Neurite Óptica/diagnóstico , Neurite Óptica/imunologia , Neurite Óptica/tratamento farmacológico , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Autoanticorpos/sangue , Encefalite/diagnóstico , Encefalite/imunologia , Encefalite/tratamento farmacológico , Metilprednisolona/uso terapêutico , Imageamento por Ressonância Magnética , Síndrome
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