RESUMO
INTRODUCTION: Neurofascin155 (NF155) is a target antigen for autoantibodies in a subset of chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: We report the cases of 4 patients with anti-NF155 immunoglobulin G4 (IgG4) antibody-positive CIDP who underwent sural nerve biopsies. RESULTS: All patients were relatively young at onset. Three patients experienced tremors, and 2 patients had severe ataxia. Although the response to intravenous immunoglobulin was poor in all patients, plasma exchange and corticosteroids were at least partially effective. Immunoadsorption plasmapheresis was performed in 1 patient but was ineffective. Electron microscopic examination of sural nerve biopsies revealed loss of paranodal transverse bands in all patients. DISCUSSION: Anti-NF155 IgG4 antibody-positive CIDP shows distinctive clinicopathological features, indicating that the IgG4 antibody is directly associated with the pathogenic mechanisms of anti-NF155 IgG4 antibody-positive CIDP. Muscle Nerve 57: 498-502, 2018.
Assuntos
Corticosteroides/uso terapêutico , Moléculas de Adesão Celular/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Fatores de Crescimento Neural/imunologia , Troca Plasmática , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Adulto , Autoanticorpos/sangue , Feminino , Humanos , Masculino , Microscopia Eletrônica , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate the morphological features of chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies directed against paranodal junctional molecules, particularly focusing on the fine structures of the paranodes. METHODS: We assessed sural nerve biopsy specimens obtained from 9 patients with CIDP with anti-neurofascin-155 antibodies and 1 patient with anti-contactin-1 antibodies. 13 patients with CIDP without these antibodies were also examined to compare pathological findings. RESULTS: Characteristic light and electron microscopy findings in transverse sections from patients with anti-neurofascin-155 and anti-contactin-1 antibodies indicated a slight reduction in myelinated fibre density, with scattered myelin ovoids, and the absence of macrophage-mediated demyelination or onion bulbs. Teased-fibre preparations revealed that segmental demyelination tended to be found in patients with relatively higher frequencies of axonal degeneration and was tandemly found at consecutive nodes of Ranvier in a single fibre. Assessment of longitudinal sections by electron microscopy revealed that detachment of terminal myelin loops from the axolemma was frequently found at the paranode in patients with anti-neurofascin-155 and anti-contactin-1 antibody-positive CIDP compared with patients with antibody-negative CIDP. Patients with anti-neurofascin-155 antibodies showed a positive correlation between the frequencies of axo-glial detachment at the paranode and axonal degeneration, as assessed by teased-fibre preparations (p<0.05). CONCLUSIONS: Paranodal dissection without classical macrophage-mediated demyelination is the characteristic feature of patients with CIDP with autoantibodies to paranodal axo-glial junctional molecules.
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Autoanticorpos/análise , Axônios/patologia , Moléculas de Adesão Celular/imunologia , Contactina 1/imunologia , Bainha de Mielina/patologia , Fatores de Crescimento Neural/imunologia , Neuroglia/patologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Nós Neurofibrosos/patologia , Nervo Sural/patologia , Adolescente , Adulto , Idoso , Axônios/imunologia , Biópsia , Feminino , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Bainha de Mielina/imunologia , Neuroglia/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Nós Neurofibrosos/imunologia , Células de Schwann/imunologia , Células de Schwann/patologia , Nervo Sural/imunologia , Adulto JovemRESUMO
OBJECTIVE: To evaluate the usefulness of 3D nerve-sheath signal increased with inked rest-tissue rapid acquisition of relaxation enhancement imaging (SHINKEI) in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: This institutional review board-approved retrospective study included 14 CIDP patients and nine normal subjects. The signal-to-noise ratio (SNR), contrast ratio (CR), and the size of the cervical ganglions and roots were measured by two raters. RESULTS: The SNRs of the ganglions and roots were larger in patients with CIDP (9.55 ± 3.87 and 9.81 ± 3.64) than in normal subjects (7.21 ± 2.42 and 5.70 ± 2.14, P < 0.0001, respectively). The CRs of the ganglions and roots were larger in patients with CIDP (0.77 ± 0.08 and 0.68 ± 0.12) than in normal subjects (0.72 ± 0.07 and 0.53 ± 0.11, P < 0.0001, respectively). The sizes of the ganglions and the roots were larger in patients with CIDP (6.44 ± 1.61 mm and 4.89 ± 1.94 mm) than in normal subjects (5.24 ± 1.02 mm and 3.39 ± 0.80 mm, P < 0.0001, respectively). CONCLUSIONS: Patients with CIDP could be distinguished from controls on 3D SHINKEI. KEY POINTS: ⢠3D SHINKEI could visualize brachial plexus with high spatial resolution. ⢠CIDP patients showed increased SNR, CR, and the size of brachial plexus. ⢠3D SHINKEI could discriminate CIDP patients from normal subjects.
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Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico por imagem , Adulto , Idoso , Plexo Braquial/diagnóstico por imagem , Feminino , Gânglios Simpáticos/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Razão Sinal-Ruído , Adulto JovemRESUMO
OBJECTIVES: To clarify the clinical features of combined central and peripheral demyelination (CCPD) via a nationwide survey. METHODS: The following characteristics were used to define CCPD: T2 high-signal intensity lesions in the brain, optic nerves or spinal cord on MRI, or abnormalities on visual-evoked potentials; conduction delay, conduction block, temporal dispersion or F-wave abnormalities suggesting demyelinating neuropathy based on nerve conduction studies; exclusion of secondary demyelination. We conducted a nationwide survey in 2012, sending questionnaires to 1332 adult and paediatric neurology institutions in Japan. RESULTS: We collated 40 CCPD cases, including 29 women. Age at onset was 31.7±14.1â years (mean±SD). Sensory disturbance (94.9%), motor weakness (92.5%) and gait disturbance (79.5%) were common. Although cerebrospinal fluid protein levels were increased in 82.5%, oligoclonal IgG bands and elevated IgG indices were detected in 7.4% and 18.5% of cases, respectively. Fifteen of 21 patients (71.4%) had abnormal visual-evoked potentials. Antineurofascin 155 antibodies were positive in 5/11 (45.5%). Corticosteroids, intravenous immunoglobulins and plasmapheresis resulted in an 83.3%, 66.7% and 87.5% improvement, respectively, whereas interferon-ß was effective in only 10% of cases. CCPD cases with simultaneous onset of central nervous system (CNS) and peripheral nervous system (PNS) involvement exhibited greater disability, but less recurrence and more frequent extensive cerebral and spinal cord MRI lesions compared to those with temporarily separated onset, whereas optic nerve involvement was more common in the latter. CONCLUSIONS: CCPD shows different characteristics from classical demyelinating diseases, and distinctive features exist between cases with simultaneous and temporarily separated onset of CNS and PNS involvement.
Assuntos
Doenças Desmielinizantes/epidemiologia , Corticosteroides/uso terapêutico , Adulto , Moléculas de Adesão Celular/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/epidemiologia , Doenças Desmielinizantes/complicações , Avaliação da Deficiência , Potenciais Evocados Visuais , Feminino , Transtornos Neurológicos da Marcha/etiologia , Inquéritos Epidemiológicos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Japão/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Fatores de Crescimento Neural/líquido cefalorraquidiano , Condução Nervosa , Doenças do Nervo Óptico/epidemiologia , Doenças do Nervo Óptico/etiologia , Doenças do Sistema Nervoso Periférico/epidemiologia , Prognóstico , Transtornos de Sensação/etiologia , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
Autoimmune nodopathy (AN), a newly established category of autoimmune disease, refers to an immune-mediated neuropathy associated with development of autoantibodies against membrane proteins, including neurofascin 186, neurofascin 155, contactin-1, and contactin-associated protein 1 located in the nodes of Ranvier or paranodes. Subclass analysis of these autoantibodies reveals predominant elevation of immunoglobulin (G4. Patients with AN show clinical and laboratory characteristics such as distal-predominant sensorimotor disturbance, sensory ataxia, poor response to intravenous immunoglobulin, and highly elevated cerebrospinal fluid protein levels. B cell-depletion therapy using an anti-CD20 monoclonal antibody is effective for patients with AN. Autoantibody measurement is beneficial not only for diagnosis but also for deciding treatment strategies for AN.
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Autoanticorpos , Humanos , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Doenças Autoimunes do Sistema Nervoso/imunologia , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/terapiaRESUMO
We describe a 44-year-old man with a complaint of atonic seizures of the left upper limb, followed by generalized seizures. Brain MRI showed isolated juxtacortical white matter T2 hyperintensity with gadolinium (Gd) enhancement of the adjacent cortical gray matter and subcortical white matter in the right frontal convexity. Treatment with levetiracetam was effective for seizure suppression, and he had no other neurological abnormalities. Human leukocyte antigen typing revealed B54 and Cw1, which indicated the possibility of neuro-Sweet disease. However, a general examination, which included vital signs and eye and skin findings, was normal. A cerebrospinal fluid test showed a mild elevation in protein levels without pleocytosis and a normal range of interleukin-6. Electroencephalography showed intermittent slow waves without epileptic discharge in the bilateral temporal lobes. We detected subtle flow voids in the pia mater of the left frontal lobe, which suggested cerebrovascular disease, and specifically, the possibility of dural arteriovenous fistulas. Computed tomography angiography showed abnormally dilated perimedullary veins in the left frontal lobe. Cerebral angiography confirmed the existence of four dural arteriovenous fistulas, which included two retrograde leptomeningeal venous drainages in the right frontal cortical veins supplied by the anterior branch of the right middle meningeal artery. The other dural arteriovenous fistulas were retrograde leptomeningeal venous drainages in the left frontal cortical veins supplied by the anterior and posterior convexity branches of the left middle meningeal artery. The patient underwent successful endovascular embolization of all dural arteriovenous fistulas with Onyx injection. A follow-up MRI showed gradual improvement of the T2 hyperintensity and Gd enhancement. He remained seizure-free for 2 years following endovascular embolization.
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Human immunodeficiency virus (HIV)-associated neuropathy is a common complication of HIV infection and has several clinical subtypes. HIV-associated chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a demyelinating neuropathy whose clinical features are known to differ from those of CIDP in the HIV-uninfected population. We herein report a case of CIDP in an HIV-infected patient who was finally diagnosed with anti-neurofascin 155 (NF155) antibody-positive neuropathy. The clinical features, including clinical findings and therapeutic responses, were typical of paranodal antibody-mediated neuropathy. To our knowledge, this is the first case of anti-NF155 antibody-associated neuropathy in an HIV-infected patient.
Assuntos
Infecções por HIV , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , HIV , Infecções por HIV/complicações , Autoanticorpos , Moléculas de Adesão Celular/uso terapêutico , Fatores de Crescimento NeuralRESUMO
Autoantibodies against nodal and paranodal proteins, such as neurofascin 140/186, neurofascin 155, contactin 1, and contactin-associated protein 1, have been identified in subsets of patients with chronic inflammatory demyelinating polyneuropathy. Their distinctive characteristics including poor response to immunoglobulin led to the establishment of a new disease entity called "autoimmune nodopathies." IgM monoclonal antibodies against myelin-associated glycoproteins cause intractable sensory-dominant demyelinating polyneuropathy. IgM anti-GM1 and IgG anti-LM1 antibodies are associated with multifocal motor neuropathy and chronic inflammatory demyelinating polyneuropathy, respectively. Monoclonal IgM against disialosyl ganglioside epitopes induces chronic ataxic neuropathy with ophthalmoplegia and cold agglutinin.
Assuntos
Polineuropatias , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Autoanticorpos , Anticorpos Monoclonais , Imunoglobulina G , Imunoglobulina MRESUMO
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is recognized as a syndrome caused by multiple pathologies. Since the 2010s, it has been clarified that autoantibodies against membranous proteins localized in the nodes of Ranvier and paranodes are positive in subsets of CIDP patients, leading to proposing a new disease concept called autoimmune nodopathies, which is independent of CIDP, in the revised international CIDP guidelines. This article reviews the significance of these autoantibodies, especially anti-neurofascin 155 and anti-contactin 1 antibodies, which have been the most prevalent and achieved a higher degree of consensus.
Assuntos
Moléculas de Adesão Celular , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Humanos , Nós Neurofibrosos/metabolismo , Nós Neurofibrosos/patologia , Autoanticorpos/metabolismo , Fatores de Crescimento NeuralRESUMO
We herein report a 77-year-old man with a 4-month history of progressive gait and sensory disturbances of the extremities. A nerve conduction study indicated demyelinating polyneuropathy. Serum IgG4 levels and anti-contactin 1 IgG4 antibodies were markedly increased. The sural nerve biopsy specimen showed IgG4-positive plasma cell infiltration in the epineurium. Treatment with steroids resulted in an amelioration of functional status, improvement of nerve conduction parameters, decreased serum IgG4 levels, and negative conversion of anti-contactin 1 antibody. Further studies are needed to clarify the significance of IgG4-positive plasma cell infiltration in anti-contactin 1 antibody-positive neuropathies.
Assuntos
Doenças do Sistema Nervoso Periférico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Masculino , Humanos , Idoso , Imunoglobulina G , Contactina 1 , Nervos Periféricos , Inflamação , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Condução Nervosa/fisiologia , AutoanticorposRESUMO
BACKGROUND AND OBJECTIVES: The objective of this study was to discover novel nodal autoantibodies in chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: We screened for autoantibodies that bind to mouse sciatic nerves and dorsal root ganglia (DRG) using indirect immunofluorescence (IFA) assays with sera from 113 patients with CIDP seronegative for anti-neurofascin 155 and anticontactin-1 antibodies and 127 controls. Western blotting, IFA assays using HEK293T cells transfected with relevant antigen expression plasmids, and cell-based RNA interference assays were used to identify target antigens. Krox20 and Periaxin expression, both of which independently control peripheral nerve myelination, was assessed by quantitative real-time PCR after application of patient and control sera to Schwann cells. RESULTS: Sera from 4 patients with CIDP, but not control sera, selectively bound to the nodal regions of sciatic nerves and DRG satellite glia (p = 0.048). The main immunoglobulin G (IgG) subtype was IgG4. IgG from these 4 patients stained a 60-kDa band on Western blots of mouse DRG and sciatic nerve lysates. These features indicated leucine-rich repeat LGI family member 4 (LGI4) as a candidate antigen. A commercial anti-LGI4 antibody and IgG from all 4 seropositive patients with CIDP showed the same immunostaining patterns of DRG and cultured rat Schwann cells and bound to the 60-kDa protein in Western blots of LGI4 overexpression lysates. IgG from 3 seropositive patients, but none from controls, bound to cells cotransfected with plasmids containing LGI4 and a disintegrin and metalloprotease domain-containing protein 22 (ADAM22), an LGI4 receptor. In cultured rat Schwann and human melanoma cells constitutively expressing LGI4, LGI4 siRNA effectively downregulated LGI4 and reduced patients' IgG binding compared with scrambled siRNA. Application of serum from a positive patient to Schwann cells expressing ADAM22 significantly reduced the expression of Krox20, but not Periaxin. Anti-LGI4 antibody-positive patients had a relatively old age at onset (mean age 58 years), motor weakness, deep and superficial sensory impairment with Romberg sign, and extremely high levels of CSF protein. Three patients showed subacute CIDP onset resembling Guillain-Barré syndrome. DISCUSSION: IgG4 anti-LGI4 antibodies are found in some elderly patients with CIDP who present subacute sensory impairment and motor weakness and are worth measuring, particularly in patients with symptoms resembling Guillain-Barré syndrome.
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Autoanticorpos , Síndrome de Guillain-Barré , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Idoso , Animais , Humanos , Camundongos , Pessoa de Meia-Idade , Ratos , Proteínas ADAM , Autoanticorpos/sangue , Autoanticorpos/química , Síndrome de Guillain-Barré/diagnóstico , Células HEK293 , Imunoglobulina G , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologiaRESUMO
Exercise-induced reflex seizures are a rare form of reflex seizures that are exclusively induced by a specific type of exercise. Many patients with exercise-induced reflex seizures exhibit drug-resistance, and are therefore advised to avoid the triggering exercise. Here, we describe a focal epilepsy patient with shadowboxing-induced reflex seizures. His semiology included focal aware seizures with speech and behavioral arrest that evolved to head version to the right, preceded by cephalic aura. We identified a specific motion that induced these seizures during shadowboxing using video-electroencephalographic recording, and the patient was able to continue boxing by avoiding this motion. We speculate that a broad brain network may be the pathological substrate of his exercise-induced reflex seizures. Identification of the specific motion that induces exercise-induced reflex seizures is useful for not only understanding the underlying pathophysiology, but also for minimizing the therapeutic restriction of the exercise.
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Charles Bonnet syndrome refers to visual hallucinations in patients with visual acuity loss or visual field loss without dementia. We report a case of Charles Bonnet syndrome following syphilitic optic neuritis. A 62-year-old man was admitted to our hospital suffering acute bilateral visual loss in a few months. On admission, he was almost blind and his optic discs were found to be atrophic on fundoscopy. In addition to increased cell counts and protein concentration in cerebrospinal fluid (CSF), serum and CSF rapid plasma reagin tests were positive. A diagnosis of syphilitic optic neuritis was made and he was treated with intravenous penicillin G (24 million units per day for 14 days) without any recovery. After treatment finished, he began to experience complex, vivid, elaborate and colored visual hallucinations. He recognized these visions as unreal and felt distressed by them. No cognitive impairment was observed on several neuropsychological tests. We diagnosed the patient as suffering from Charles Bonnet syndrome. Brain MRI revealed diffuse mild atrophy of the cerebral cortex and multiple T2 high signal intensity lesions in the deep cerebral white matter. Single photon emission computed tomography revealed decreased regional cerebral blood flow in bilateral medial occipital lobes. Administration of olanzapine resulted in a partial remission of visual hallucinations. Charles Bonnet syndrome following syphilitic optic neuritis is rare. In the present case, visual loss and dysfunction of bilateral medial occipital lobes may have triggered the visual hallucinations, which were alleviated by olanzapine.
Assuntos
Alucinações/etiologia , Neurossífilis/complicações , Neurite Óptica/complicações , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Combined central and peripheral demyelination (CCPD) causes demyelination in both the central and peripheral nervous systems. Anti-neurofascin 155 antibody plays an important pathogenic role in CCPD, but evidence concerning an association between this antibody and CCPD remains inconclusive. Although there have been no reports of precedent optic neuritis developing into CCPD, we herein report a Japanese man in whom optic neuritis recurred four times over nine years and who developed CCPD without positive anti-neurofascin 155 antibody. This case suggests the possibility of developing CCPD after optic nerve neuritis and the existence of an unknown antibody that induces CCPD.
Assuntos
Doenças Desmielinizantes , Neurite Óptica , Doenças Desmielinizantes/diagnóstico , Humanos , Japão , Masculino , Neurite Óptica/diagnóstico , Neurite Óptica/etiologiaAssuntos
Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/epidemiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/epidemiologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Japão/epidemiologia , Masculino , Esclerose Múltipla/diagnóstico , Fatores de TempoAssuntos
Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/terapia , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/terapia , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/terapia , Adulto , Feminino , Humanos , Masculino , Esclerose Múltipla/diagnóstico , Guias de Prática Clínica como AssuntoRESUMO
A 41-year-old man noticed numbness of the fingers and toes, and gradually developed limb weakness and sensory impairment. The patient was diagnosed with typical chronic inflammatory demyelinating polyradiculoneuropathy. Over the course of clinical diagnosis, the limb and trunk ataxia, and finger tremor became prominent, and the presence anti-neurofascin-155 antibody was examined and confirmed positive. The effects of corticosteroids, intravenous immunoglobulin, and plasma apheresis were limited, and the disease progressed slowly and noticeably. Therefore, cyclosporine was introduced as treatment, and the patient's weakness and ataxia significantly improved. Rituximab treatment is expected to be effective in patients with the same antibody and immunosuppressant treatment may be useful in intractable cases.
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Autoanticorpos/sangue , Moléculas de Adesão Celular/imunologia , Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Fatores de Crescimento Neural/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Adulto , Biomarcadores/sangue , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Masculino , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologiaRESUMO
The patient was a 40-year-old woman who was previously diagnosed with systemic lupus erythematosus and myasthenia gravis and had received prednisolone and tacrolimus for more than 7 years. In February 2017, she noticed pain in her lower back and weakness of the lower limbs, and was referred to our hospital on day 5. She had shingles in the right lower thoracic dermatomes and Brown-Séquard syndrome with right-sided dominant weakness in her lower limbs and left-sided superficial sensory disturbance below the L1 level. Varicella zoster virus (VZV)-associated myelopathy was suspected because of her symptoms and clinical findings. Despite the immediate administration of intravenous acyclovir after hospitalization, she lost consciousness and experienced a seizure related to cerebral hemorrhage in the left temporal lobe on the night of day 5. MRI showed enhanced lesions along the spinal cord and leptomeninges of the brainstem and temporal lobe. VZV-IgG and VZV-DNA were positive in the cerebrospinal fluid. Based on these clinical features and laboratory findings, she was diagnosed as VZV-associated vasculopathy and myelopathy. She subsequently had multiple cerebral infractions and hemorrhage, and developed sudden cardiopulmonary arrest on day 6, culminating in death on day 17. Autopsy showed that inflammatory mononuclear cells had infiltrated the vascular walls of the spinal cord. Immunohistochemistry revealed that some neurons and macrophages in the white matter of the spinal cord were positive for VZV. In addition, atrophic neurons, satellite cells surrounding these neurons, and infiltrating macrophages were immune-positive for VZV at the L2 dorsal root ganglia. These findings were consistent with VZV-associated vasculopathy and myelitis. Under immunosuppressive conditions, VZV can cause shingles and neuronal complications such as vasculopathy and myelitis, which are sometimes fatal despite the immediate administration of intravenous acyclovir. New treatment drugs or drugs to prevent VZV activation are desired.
Assuntos
Encefalite por Varicela Zoster/diagnóstico , Encefalite por Varicela Zoster/etiologia , Encefalite Viral/diagnóstico , Encefalite Viral/etiologia , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Prednisolona/efeitos adversos , Tacrolimo/efeitos adversos , Adulto , Autopsia , Sistema Nervoso Central/diagnóstico por imagem , Sistema Nervoso Central/patologia , Sistema Nervoso Central/virologia , Encefalite por Varicela Zoster/patologia , Encefalite por Varicela Zoster/virologia , Encefalite Viral/patologia , Encefalite Viral/virologia , Evolução Fatal , Feminino , Humanos , Imageamento por Ressonância Magnética , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To characterize the frequency and patterns of optic, trigeminal, and facial nerve involvement by neuroimaging and electrophysiology in IgG4 anti-neurofascin 155 antibody-positive (NF155+ ) chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Thirteen IgG4 NF155+ CIDP patients with mean onset age of 34 years (11 men) were subjected to neurological examination, blink reflex, and visual-evoked potential (VEP) testing, and axial and/or coronal T2-weighted head magnetic resonance imaging (MRI). RESULTS: Among 13 patients, facial sensory impairment, facial weakness, and apparent visual impairment were observed in three (23.1%), two (15.4%), and two (15.4%) patients, respectively. All 12 patients tested had blink reflex abnormalities: absent and/or delayed R1 in 11 (91.7%), and absent and/or delayed R2 in 10 (83.3%). R1 latencies had strong positive correlations with serum anti-NF155 antibody levels (r = 0.9, P ≤ 0.0001 on both sides) and distal and F wave latencies of the median and ulnar nerves. Absent and/or prolonged VEPs were observed in 10/13 (76.9%) patients and 17/26 (65.4%) eyes. On MRI, hypertrophy, and high signal intensity of trigeminal nerves were detected in 9/13 (69.2%) and 10/13 (76.9%) patients, respectively, whereas optic nerves were normal in all patients. The intra-orbital trigeminal nerve width on coronal sections showed a significant positive correlation with disease duration. INTERPRETATION: Subclinical demyelination frequently occurs in the optic, trigeminal, and facial nerves in IgG4 NF155+ CIDP, suggesting that both central and peripheral myelin structures of the cranial nerves are involved in this condition, whereas nerve hypertrophy only develops in myelinated peripheral nerve fibers.
Assuntos
Autoanticorpos/sangue , Moléculas de Adesão Celular/imunologia , Doenças do Nervo Facial , Fatores de Crescimento Neural/imunologia , Doenças do Nervo Óptico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Doenças do Nervo Trigêmeo , Adulto , Idoso , Piscadela/fisiologia , Potenciais Evocados Visuais/fisiologia , Doenças do Nervo Facial/etiologia , Doenças do Nervo Facial/imunologia , Doenças do Nervo Facial/patologia , Doenças do Nervo Facial/fisiopatologia , Feminino , Células HEK293 , Humanos , Imunoglobulina G , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Condução Nervosa/fisiologia , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/imunologia , Doenças do Nervo Óptico/patologia , Doenças do Nervo Óptico/fisiopatologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Doenças do Nervo Trigêmeo/etiologia , Doenças do Nervo Trigêmeo/imunologia , Doenças do Nervo Trigêmeo/patologia , Doenças do Nervo Trigêmeo/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated peripheral neuropathy that is currently classified into several clinical subtypes, which are presumed to have different pathogenic mechanisms. Recently, studies identified a subgroup of patients with CIDP who were positive for IgG4 autoantibodies against paranodal proteins, such as neurofascin-155 and contactin-1, who respond poorly to first-line therapies for typical CIDP, including intravenous immunoglobulin therapy. OBJECTIVE: This study aims to evaluate the efficacy and safety of intravenous rituximab according to IgG4 autoantibody status in patients with refractory CIDP. METHODS: The Evaluation of the Efficacy and Safety of Rituximab in Refractory CIDP Patients with IgG4 Autoantibodies in the Exploratory Clinical (RECIPE) trial consists of 2 cohorts: a multicenter, placebo-controlled, randomized study cohort of 15 patients with IgG4 autoantibody-positive CIDP (rituximab:placebo = 2:1) and an open-label trial cohort of 10 patients with antibody-negative CIDP. The primary endpoint is improvement in functional outcome assessed using the adjusted Inflammatory Neuropathy Cause and Treatment Disability Scale score at 26, 38, or 52 weeks after the start of treatment with rituximab in patients with CIDP and anti-paranodal protein antibodies. Secondary outcome measures include grip strength, manual muscle testing sum scores, results of nerve conduction studies, and other functional scales. RESULTS: We plan to enroll 25 cases for the full analysis set. Recruitment is ongoing, with 14 patients enrolled as of January 2020. Enrollment will close in September 2020, and the study is planned to end in December 2021. CONCLUSIONS: This randomized controlled trial will determine if rituximab is safe and effective in patients with anti-paranodal antibodies. An open-label study will provide additional data on the effects of rituximab in patients with antibody-negative CIDP. The results of the RECIPE trial are expected to provide evidence for the positioning of rituximab as a pathogenesis-based therapeutic for refractory CIDP. TRIAL REGISTRATION: ClinicalTrials.gov NCT03864185, https://clinicaltrials.gov/ct2/show/NCT03864185 ; The Japan Registry of Clinical Trials jRCT2041180037, https://jrct.niph.go.jp/en-latest-detail/jRCT2041180037. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17117.