RESUMO
RATIONALE: Miller-Fisher syndrome (MFS) is a rare subtype of Guillain-Barre syndrome with classic features of ataxia, areflexia, and ophthalmoplegia that can be caused by a preceding infection including COVID-19. We present a current, asymptomatic thrombocytopenic COVID-19 infection as a cause of MFS in a 60-year-old male with a concurrent chronic immune neuropathy. PATIENT CONCERNS: A 60-year-old male presenting with acute symptoms of MFS including ataxia, areflexia, and ophthalmoplegia on a chronic immune neuropathy for at least 1 year and concurrent asymptomatic COVID-19 positive infection. DIAGNOSIS: MFS suspected secondary to a current thrombocytopenic COVID-19 infection. INTERVENTIONS: Five days of intravenous immune globulin with continued monthly intravenous immune globulin as an outpatient, follow-up long-term in a neuromuscular clinic, electromyography as an outpatient, and continued physical therapy. OUTCOMES: The patient significantly improved after initial treatment. LESSONS: The full effect of COVID-19 on the various Guillain-Barre syndrome subtypes is unknown, although it clearly can be a cause of the various variants including being caused by a current, asymptomatic infection.
Assuntos
COVID-19 , Imunoglobulinas Intravenosas , Síndrome de Miller Fisher , Humanos , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/imunologia , Masculino , COVID-19/complicações , COVID-19/imunologia , Pessoa de Meia-Idade , Imunoglobulinas Intravenosas/uso terapêutico , SARS-CoV-2 , TrombocitopeniaRESUMO
Importance: The discovery of the anti-GQ1b antibody has expanded the nosology of classic Miller Fisher syndrome to include Bickerstaff brainstem encephalitis, Guillain-Barré syndrome with ophthalmoplegia, and acute ophthalmoplegia without ataxia, which have been brought under the umbrella term anti-GQ1b antibody syndrome. It seems timely to define the phenotypes of anti-GQ1b antibody syndrome for the proper diagnosis of this syndrome with diverse clinical presentations. This review summarizes these syndromes and introduces recently identified subtypes. Observations: Although ophthalmoplegia is a hallmark of anti-GQ1b antibody syndrome, recent studies have identified this antibody in patients with acute vestibular syndrome, optic neuropathy with disc swelling, and acute sensory ataxic neuropathy of atypical presentation. Ophthalmoplegia associated with anti-GQ1b antibody positivity is complete in more than half of the patients but may be monocular or comitant. The prognosis is mostly favorable; however, approximately 14% of patients experience relapse. Conclusions and Relevance: Anti-GQ1b antibody syndrome may present diverse neurological manifestations, including ophthalmoplegia, ataxia, areflexia, central or peripheral vestibulopathy, and optic neuropathy. Understanding the wide clinical spectrum may aid in the differentiation and management of immune-mediated neuropathies with multiple presentations.
Assuntos
Autoanticorpos , Gangliosídeos , Síndrome de Miller Fisher , Oftalmoplegia , Humanos , Gangliosídeos/imunologia , Oftalmoplegia/imunologia , Oftalmoplegia/diagnóstico , Síndrome de Miller Fisher/imunologia , Síndrome de Miller Fisher/diagnóstico , Autoanticorpos/sangue , Autoanticorpos/imunologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/diagnósticoRESUMO
Fisher syndrome is recognized as a variant of Guillain-Barré syndrome, encompassing acute onset immune-mediated neuropathies marked by the classical triad of ataxia, areflexia, and ophthalmoplegia. Generally, Fisher syndrome follows a self-limited course with a good prognosis. Ophthalmoplegia, typically bilateral, progresses to complete external ophthalmoplegia within 1-2 weeks. Ataxia, often very severe, may cause an inability to walk without support despite normal strength. Fisher syndrome is also frequently concomitant with additional clinical features, including ptosis, internal ophthalmoplegia, facial nerve palsy, sensory deficits, and bulbar palsy. The confirmation of an antecedent infection is often established. Among the ganglioside antibodies, anti-GQ1b antibodies exhibit positivity in over 80% of patients. The syndrome manifests in three distinct types: a partial subtype exhibiting only a subset of the triad symptoms, Bickerstaff's brainstem encephalitis marked by impaired consciousness and pyramidal tract signs, and an overlapping subtype with Guillain-Barré syndrome, characterized by weakness in the extremities.
Assuntos
Síndrome de Miller Fisher , Humanos , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/imunologia , Síndrome de Miller Fisher/terapia , Síndrome de Miller Fisher/fisiopatologia , Gangliosídeos/imunologia , Prognóstico , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/terapiaRESUMO
BACKGROUND AND PURPOSE: Antiganglioside antibodies (AGAs) might be involved in the etiopathogenesis of many neurological diseases, such as Miller-Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS). Available comprehensive reference data regarding AGA positivity rates and cross-responsiveness among AGAs (where one line immunoblot is positive for ≥1 AGA) during routine clinical care are scant. METHODS: In this 10-year monocentric retrospective study, 3560 immunoglobulin (Ig) G and IgM line blots (GA Generic Assays' Anti-Ganglioside Dot kit) obtained using cerebrospinal fluid (CSF) and serum samples from 1342 patients were analyzed for AGA positivity in terms of 14 diagnosis categories and AGA cross-responsiveness. RESULTS: Of all 3560 line blots 158 (4.4%) and of all CSF samples 0.4% (4/924) CSF line blots were AGA positive. For serum IgG, blots with positivity rates higher than the standard deviation of 15.6% were associated with MFS (GD3, GD1a, GT1a and GQ1b) and acute motor axonal neuropathy (AMAN) (GM1, GD1a and GT1a). For serum IgM, blots with positivity rates higher than the standard deviation of 8.1% were associated with AMAN (GM2, GT1a and GQ1b), MFS (GM1, GT1a and GQ1b), multifocal motor neuropathy (MMN) (GM1, GM2 and GQ1b) and chronic inflammatory demyelinating polyneuropathy (CIDP) (GM1). Cross-responsiveness was observed in 39.6% of all positive serum AGA. CONCLUSIONS: Testing for AGAs during routine clinical care rarely led to positive findings, both in serum and even less in CSF, except for the diagnoses AMAN, MFS, MMN and CIDP. Nonspecific findings found as cross-responsiveness between different AGA samples occur frequently, impacting the positivity of most AGA subtypes.
Assuntos
Autoanticorpos , Gangliosídeos , Humanos , Estudos Retrospectivos , Gangliosídeos/imunologia , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Feminino , Masculino , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Síndrome de Miller Fisher/sangue , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/imunologia , Síndrome de Miller Fisher/líquido cefalorraquidiano , Imunoglobulina M/sangue , Imunoglobulina M/líquido cefalorraquidiano , Adulto , Síndrome de Guillain-Barré/sangue , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/imunologia , IdosoRESUMO
Guillain-Barré syndrome (GBS) is an ascending demyelinating polyneuropathy often associated with recent infection. Miller Fisher syndrome represents a variant with predominant facial and cranial nerve involvement, although Miller Fisher and Guillain-Barré overlap syndromes can occur. Guillain-Barré spectrum syndromes have been thought to be rare among solid organ transplant recipients. We describe an immunocompromised patient with a liver transplant who presented with ophthalmoplegia and bulbar deficits. His symptoms rapidly progressed to a state of descending paralysis involving the diaphragm; he then developed acute respiratory failure and eventually developed quadriparesis. Electromyography and a nerve conduction study demonstrated a severe sensorimotor axonal polyneuropathy consistent with Miller Fisher variant Guillain-Barré syndrome. Despite several negative nasopharyngeal swabs for COVID-19 polymerase chain reaction, a serology for SARS-CoV-2 IgG was positive. He was diagnosed with Miller Fisher-Guillain-Barré overlap syndrome with rapid recovery following treatment with plasma exchange. Although Guillain-Barré is a rare complication in solid organ transplant recipients, this case highlights the importance of rapid diagnosis and treatment of neurologic complications in transplant patients. Furthermore, it demonstrates a possible case of neurological complications from COVID-19 infection.
Assuntos
COVID-19/complicações , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/virologia , Síndrome de Miller Fisher/imunologia , Síndrome de Miller Fisher/virologia , Síndrome de Guillain-Barré/terapia , Humanos , Hospedeiro Imunocomprometido , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/terapia , Plasmaferese , SARS-CoV-2 , TransplantadosRESUMO
Miller-Fisher syndrome (MFS) together with Guillan-Barré syndrome (GBS) and Bickerstaff brainstem encephalitis (BBE) are considered to form a continuous clinical spectrum of the same disease, possibly affecting the peripheral and/or central nervous systems, with monophasic symptoms. The frequency of overlapping clinical signs and the risk of recurrence are independent and very low, but no cases of GQ1b-seropositive recurrent MFS overlapping with GBS and BBE have been described so far. Here, we describe for the first time an atypical case of recurrent GQ1b-seropositive MFS overlapping GBS and BBE, 12 years after a previous GQ1b-seronegative typical MFS episode. Our case expands the clinical spectrum of recurrent MFS, and it should prompt clinicians to investigate the presence of anti-ganglioside antibodies in recurrent MFS even when these were negative in the previous episode, especially in those presenting with overlapping spectrum symptoms and a critically ill picture during the second episode.
Assuntos
Encefalite , Síndrome de Guillain-Barré , Síndrome de Miller Fisher , Adulto , Autoanticorpos/imunologia , Autoantígenos/imunologia , Tronco Encefálico , Encefalite/imunologia , Encefalite/fisiopatologia , Feminino , Gangliosídeos/imunologia , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Síndrome de Miller Fisher/imunologia , Síndrome de Miller Fisher/fisiopatologia , RecidivaRESUMO
BACKGROUND: Bickerstaff's brainstem encephalitis (BBE) and Fisher syndrome (FS) are immune-mediated diseases associated with anti-ganglioside antibodies, specifically the anti-GQ1b IgG antibody. These two diseases potentially lie on a continuous spectrum with Guillain-Barré Syndrome (GBS). There are some reports of family cases of GBS and fewer of FS. However, there are no reports of family cases of BBE and FS. CASE PRESENTATION: We report a familial case of an 18-year-old son who had BBE and his 52-year-old mother diagnosed with FS within 10 days. The son showed impaired consciousness 1 week after presenting with upper respiratory symptoms and was brought to our hospital by his mother. He showed decreased tendon reflexes, limb ataxia, albuminocytologic dissociation in his spinal fluid, and positive serum anti-GQ1b antibodies. Haemophilus influenzae was cultured from his sputum. He was diagnosed with BBE and treated with intravenous immunoglobulin (IVIg) therapy, which led to an improvement in symptoms. The mother presented with upper respiratory symptoms 3 days after her son was hospitalized. Seven days later, she was admitted to the hospital with diplopia due to limited abduction of the left eye. She showed mild ataxia and decreased tendon reflexes. Her blood was positive for anti-GQ1b antibodies. She was diagnosed with FS and treated with IVIg, which also led to symptomatic improvement. CONCLUSIONS: There are no previous reports of familial cases of BBE and FS; therefore, this valuable case may contribute to the elucidation of the relationship between genetic predisposition and the pathogenesis of BBE and FS.
Assuntos
Encefalite/imunologia , Gangliosídeos/imunologia , Predisposição Genética para Doença , Síndrome de Miller Fisher/imunologia , Adolescente , Tronco Encefálico/patologia , Encefalite/tratamento farmacológico , Encefalite/patologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/tratamento farmacológico , Síndrome de Miller Fisher/patologia , Mães , Núcleo FamiliarRESUMO
RATIONALE: The Miller Fisher syndrome (MFS) is an acute polyradiculoneuritis regarded as an uncommon clinical variant of the Guillain-Barre syndrome (GBS). It is characterized by the clinical triad of ophthalmoplegia, ataxia, and areflexia. The diagnosis of MFS is based on clinical presentation, presence of albuminocytologic dissociation in the cerebrospinal fluid (CSF), and normal brain imaging results. The presence of anti-ganglioside antibodies (GQlb) in the serum is helpful for the diagnosis. A history of upper respiratory tract infection or diarrhea 3âdays to 6âweeks before the onset of MFS is common. However, there are some patients with atypical manifestations who are difficult to diagnose. Here, we present an incomplete form of MFS where antibodies against GQ1b were detected in the serum following an Epstein Barr virus (EBV) infection. PATIENT CONCERNS: A 77-year-old Chinese woman was admitted to the hospital with acute diplopia and right blepharoptosis. She had a history of mild upper respiratory tract infection 2 weeks ago. In 1âweek, the symptoms rapidly progressed into bilateral ophthalmoplegia and hyporeflexia of the limbs without ataxia. CSF analysis on the third day after onset was normal, without albuminocytologic dissociation. EBV immunoglobulin G (IgG) antibodies were detected in the CSF. GQ1b and GD1b IgG antibodies were positive in the serum and negative in the CSF. No responsible lesion was found on brain imaging examination. DIAGNOSES: In accordance with the progressive bilateral ophthalmoplegia and hyporeflexia, the history of upper respiratory tract infection, the detection of EBV and GQ1b antibodies, and the negative brain imaging examination, the diagnosis of MFS was confirmed. INTERVENTIONS: The patient was administered intravenous immunoglobulin for 5âdays. OUTCOMES: She had a favorable outcome after treatment. At the 6-week follow-up, bilateral ocular movement limitation and tendon reflexes had recovered. LESSONS: The diagnosis of MFS can be challenging, especially when encountered with incomplete symptoms and normal CSF results. Attention should be paid to the presence of anti-GQ1b IgG antibodies when the clinical manifestations are incomplete. Furthermore, EBV primary infection could be associated with MFS and considered a potential causative agent.
Assuntos
Infecções por Vírus Epstein-Barr/complicações , Gangliosídeos/imunologia , Síndrome de Miller Fisher/etiologia , Síndrome de Miller Fisher/imunologia , Idoso , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/tratamento farmacológicoAssuntos
Autoanticorpos/imunologia , Síndrome Miastênica de Lambert-Eaton/fisiopatologia , Síndrome de Miller Fisher/fisiopatologia , Condução Nervosa/fisiologia , Potenciais de Ação/fisiologia , Idoso , Doenças Assintomáticas , Ataxia/fisiopatologia , Blefaroptose/fisiopatologia , Canais de Cálcio Tipo P/imunologia , Canais de Cálcio Tipo Q/imunologia , Diplopia/fisiopatologia , Eletrodiagnóstico , Eletromiografia , Feminino , Gangliosídeos/imunologia , Humanos , Hipestesia/fisiopatologia , Síndrome Miastênica de Lambert-Eaton/complicações , Síndrome Miastênica de Lambert-Eaton/imunologia , Nervo Mediano/fisiopatologia , Síndrome de Miller Fisher/complicações , Síndrome de Miller Fisher/imunologia , Debilidade Muscular/fisiopatologia , Midríase/fisiopatologia , Músculos Oculomotores/fisiopatologia , Nervo Tibial/fisiopatologia , Nervo Ulnar/fisiopatologiaRESUMO
Guillain-Barré syndrome (GBS), including its variant Miller Fisher syndrome (MFS), is an acute peripheral neuropathy that involves autoimmune mechanisms leading to the production of autoantibodies to gangliosides; sialic acid-containing glycosphingolipids. Although association with various genetic polymorphisms in the major histocompatibility complex (MHC) is shown in other autoimmune diseases, GBS is an exception, showing no such link. No significant association was found by genome wide association studies, suggesting that GBS is not associated with common variants. To address the involvement of rare variants in GBS, we analyzed Siglec-10, a sialic acid-recognizing inhibitory receptor expressed on B cells. Here we demonstrate that two rare variants encoding R47Q and A108V substitutions in the ligand-binding domain are significantly accumulated in patients with GBS. Because of strong linkage disequilibrium, there was no patient carrying only one of them. Recombinant Siglec-10 protein containing R47Q but not A108V shows impaired binding to gangliosides. Homology modeling revealed that the R47Q substitution causes marked alteration in the ligand-binding site. Thus, GBS is associated with a rare variant of the SIGLEC10 gene that impairs ligand binding of Siglec-10. Because Siglec-10 regulates antibody production to sialylated antigens, our finding suggests that Siglec-10 regulates development of GBS by suppressing antibody production to gangliosides, with defects in its function predisposing to disease.
Assuntos
Gangliosídeos/imunologia , Predisposição Genética para Doença , Síndrome de Guillain-Barré/imunologia , Lectinas/imunologia , Mutação de Sentido Incorreto/imunologia , Polimorfismo de Nucleotídeo Único/imunologia , Receptores de Superfície Celular/imunologia , Alelos , Sequência de Aminoácidos , Autoanticorpos/imunologia , Sítios de Ligação/genética , Feminino , Gangliosídeos/metabolismo , Frequência do Gene , Genótipo , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/metabolismo , Humanos , Lectinas/genética , Lectinas/metabolismo , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/genética , Síndrome de Miller Fisher/imunologia , Síndrome de Miller Fisher/metabolismo , Mutação de Sentido Incorreto/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Homologia de Sequência de AminoácidosRESUMO
OBJECTIVE: To determine whether IgG subclasses of antiparanodal autoantibodies are related to disease course and treatment response in acute- to subacute-onset neuropathies, we retrospectively screened 161 baseline serum/CSF samples and 66 follow-up serum/CSF samples. METHODS: We used ELISA and immunofluorescence assays to detect antiparanodal IgG and their subclasses and titers in serum/CSF of patients with Guillain-Barré syndrome (GBS), recurrent GBS (R-GBS), Miller-Fisher syndrome, and acute- to subacute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). We evaluated clinical data retrospectively. RESULTS: We detected antiparanodal autoantibodies with a prevalence of 4.3% (7/161), more often in A-CIDP (4/23, 17.4%) compared with GBS (3/114, 2.6%). Longitudinal subclass analysis in the patients with GBS revealed IgG2/3 autoantibodies against Caspr-1 and against anti-contactin-1/Caspr-1, which disappeared at remission. At disease onset, patients with A-CIDP had IgG2/3 anti-Caspr-1 and anti-contactin-1/Caspr-1 or IgG4 anti-contactin-1 antibodies, IgG3 being associated with good response to IV immunoglobulins (IVIg). In the chronic phase of disease, IgG subclass of one patient with A-CIDP switched from IgG3 to IgG4. CONCLUSION: Our data (1) confirm and extend previous observations that antiparanodal IgG2/3 but not IgG4 antibodies can occur in acute-onset neuropathies manifesting as monophasic GBS, (2) suggest association of IgG3 to a favorable response to IVIg, and (3) lend support to the hypothesis that in some patients, an IgG subclass switch from IgG3 to IgG4 may be the correlate of a secondary progressive or relapsing course following a GBS-like onset.
Assuntos
Autoanticorpos , Moléculas de Adesão Celular Neuronais/imunologia , Contactina 1/imunologia , Síndrome de Guillain-Barré , Imunoglobulina G , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica , Adulto , Autoanticorpos/sangue , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/imunologia , Seguimentos , Síndrome de Guillain-Barré/sangue , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Síndrome de Guillain-Barré/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina G/imunologia , Síndrome de Miller Fisher/sangue , Síndrome de Miller Fisher/líquido cefalorraquidiano , Síndrome de Miller Fisher/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/sangue , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/líquido cefalorraquidiano , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Estudos RetrospectivosRESUMO
The immune-mediated neuropathies are a broad category of diseases differentiated by time course, affected nerve fibers, and disease associations. This article spans the common, well-defined inflammatory demyelinating polyradiculoneuropathies (Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy) to the rarer, acquired demyelinating neuropathy variants (Miller-Fisher syndrome and multifocal motor neuropathy), vasculitic neuropathies, and sensory neuronopathies (dorsal root ganglionopathies). These case studies illustrate the characteristic clinical patterns of the immune-mediated neuropathies encountered in neurologic practice. Recommendations for diagnostic evaluation and treatment approach accompany each case. Prompt recognition of these disorders is imperative; delays in treatment may result in prolonged morbidity and permanent disability.
Assuntos
Síndrome de Guillain-Barré/diagnóstico por imagem , Síndrome de Guillain-Barré/imunologia , Síndrome de Miller Fisher/diagnóstico por imagem , Síndrome de Miller Fisher/imunologia , Polineuropatias/diagnóstico por imagem , Polineuropatias/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/diagnóstico por imagem , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Síndrome de Guillain-Barré/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/terapia , Polineuropatias/terapia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapiaRESUMO
A 56-year-old man with a remote history of bilateral recurrent facial palsies presented with a week of ophthalmoplegia with intact deep tendon reflexes and lack of ataxia, cerebrospinal fluid with albuminocytologic dissociation and elevated serum anti-ganglioside Q1b (GQ1b) IgG antibody. We diagnosed the patient with acute ophthalmoplegia without ataxia, a condition under the spectrum of anti-GQ1b antibody syndromes which also includes Miller Fisher syndrome. Given the rarity of recurrent facial palsies and anti-GQ1b antibody syndromes as well as reports associating facial palsies and this syndrome, we suggest that our case may be an unusual presentation of an anti-GQ1b antibody syndrome beginning with recurrent facial palsies several years prior to ophthalmoplegia. Prior studies of human nerves provide insight into the pathophysiology, including ganglioside distribution and cross-reactivities underlying the heterogeneity of anti-GQ1b antibody syndromes. This report may expand the differential diagnosis in patients with recurrent facial palsies and broaden the phenotype of anti-GQ1b syndromes.
Assuntos
Autoanticorpos/sangue , Gangliosídeos/sangue , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/imunologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Miller-Fisher syndrome and Bickerstaff brainstem encephalitis, among others, constitute the anti-GQ1b syndrome, with a common immune pathophysiologic pathway characterized by the presence of anti-GQ1b antibodies, which react against the different nervous system GQ1b sites according to their different accessibility. The Miller-Fisher syndrome has a prevalence of 0.09 cases per 100 000 people-year but there are not epidemiological studies about Bickerstaff brainstem encephalitis, that it seems to be less frequent. In spite of having a good natural outcome, the immunoglobulin administration has been established as efficacious at improving it. A twelveyear- old boy suffering from Miller-Fisher-Bickerstaff syndrome after an acute Campylobacter jejuni diarrhea with positive titers of anti-GQ1b and anti-QGT1a antibodies is presented. We communicate a very uncommon pediatric disease with the aim of warning about the importance of its early suspicion and the need of specific laboratory determinations.
El síndrome anti-GQ1b reúne el síndrome de Miller-Fisher y la encefalitis del tronco cerebral de Bickerstaff, entre otras entidades. Tienen etiopatogenia común, constituida por la presencia de anticuerpos anti-GQ1b que reaccionan contra los sitios GQ1b del sistema nervioso según sea su accesibilidad. La prevalencia anual del síndrome de Miller-Fisher es de 0,09 casos por 100 000 habitantes por año y no existen estudios epidemiológicos sobre la encefalitis del tronco cerebral de Bickerstaff, que sería menos frecuente. De evolución natural hacia la mejoría, se beneficia del tratamiento con gammaglobulina endovenosa. Se presenta a un paciente de 12 años con síndrome de Miller- FisherBickerstaff tras un episodio de diarrea aguda por Campylobacter jejuni en el que los anticuerpos anti-GQ1b resultaron positivos. Es nuestro objetivo comunicar sobre un síndrome de presentación poco habitual en pediatría a fin de advertir acerca de la necesidad de su sospecha precoz y solicitud de estudios de laboratorio específicos.
Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Encefalite/diagnóstico , Gangliosídeos/imunologia , Síndrome de Miller Fisher/diagnóstico , Autoanticorpos/sangue , Autoantígenos/sangue , Biomarcadores/sangue , Criança , Encefalite/sangue , Encefalite/imunologia , Encefalite/fisiopatologia , Humanos , Masculino , Síndrome de Miller Fisher/sangue , Síndrome de Miller Fisher/imunologia , Síndrome de Miller Fisher/fisiopatologia , SíndromeRESUMO
OBJECTIVE: To report 2 patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented acutely with Miller Fisher syndrome and polyneuritis cranialis, respectively. METHODS: Patient data were obtained from medical records from the University Hospital "Príncipe de Asturias," Alcalá de Henares, and the University Hospital "12 de Octubre," Madrid, Spain. RESULTS: A 50-year-old man presented with anosmia, ageusia, right internuclear ophthalmoparesis, right fascicular oculomotor palsy, ataxia, areflexia, albuminocytologic dissociation, and positive testing for anti-GD1b-immunoglobulin G antibody. Five days previously, he had developed a cough, malaise, headache, low back pain, and fever. A 39-year-old man presented with ageusia, bilateral abducens palsy, areflexia, and albuminocytologic dissociation. Three days previously, he had developed diarrhea, a low-grade fever, and poor general condition. Oropharyngeal swab test for SARS-CoV-2 by qualitative real-time reverse transcriptase PCR assay was positive in both patients and negative in the CSF. The first patient was treated with IV immunoglobulin and the second with acetaminophen. Two weeks later, both patients made a complete neurologic recovery, except for residual anosmia and ageusia in the first case. CONCLUSIONS: Our 2 cases highlight the rare occurrence of Miller Fisher syndrome and polyneuritis cranialis during the coronavirus disease 2019 (COVID-19) pandemic. These neurologic manifestations may occur because of an aberrant immune response to COVID-19. The full clinical spectrum of neurologic symptoms in patients with COVID-19 remains to be characterized.
Assuntos
Infecções por Coronavirus/fisiopatologia , Doenças dos Nervos Cranianos/fisiopatologia , Síndrome de Miller Fisher/fisiopatologia , Neurite (Inflamação)/fisiopatologia , Pneumonia Viral/fisiopatologia , Adulto , Ageusia/etiologia , Ageusia/fisiopatologia , Betacoronavirus , COVID-19 , Infecções por Coronavirus/complicações , Doenças dos Nervos Cranianos/etiologia , Doenças dos Nervos Cranianos/imunologia , Gangliosídeos/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/etiologia , Síndrome de Miller Fisher/imunologia , Neurite (Inflamação)/etiologia , Neurite (Inflamação)/imunologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Pandemias , Pneumonia Viral/complicações , SARS-CoV-2 , Índice de Gravidade de Doença , EspanhaRESUMO
Ophthalmoplegia, ataxia and areflexia characterise the clinical triad of Miller-Fisher Syndrome (MFS). When the disease presents acutely, it can mimic posterior circulation stroke. We describe a case of an adult patient presenting with sudden dizziness, diplopia, vomiting, and loss of balance. She was initially managed as a case of a brainstem stroke, but the progression of craniopathies without deterioration in sensorium coupled with areflexia clinched the diagnosis of MFS two days into her admission. On the third day, her MFS progressed rapidly to acute motor and sensory axonal neuropathy (AMSAN) variant of Guillain-Barre Syndrome, a rare occurrence in patients with MFS, with only four reported cases including our own. Among the four cases, ours is the only one still non-ambulatory eight months after the initial onset of symptoms. The case highlights the importance of early recognition of MFS in patients with ophthalmoplegia and ataxia despite initially normal reflexes.
Assuntos
Síndrome de Guillain-Barré/diagnóstico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndrome de Miller Fisher/diagnóstico , Recuperação de Função Fisiológica/fisiologia , Diagnóstico Diferencial , Diplopia/etiologia , Progressão da Doença , Tontura/etiologia , Feminino , Síndrome de Guillain-Barré/tratamento farmacológico , Síndrome de Guillain-Barré/imunologia , Síndrome de Guillain-Barré/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Síndrome de Miller Fisher/tratamento farmacológico , Síndrome de Miller Fisher/imunologia , Síndrome de Miller Fisher/fisiopatologia , Exame Neurológico , Equilíbrio Postural , Recuperação de Função Fisiológica/imunologia , Fatores de Tempo , Resultado do Tratamento , Vômito/etiologiaAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Autoanticorpos/sangue , Gangliosídeos/imunologia , Síndrome de Miller Fisher/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/sangue , Síndrome de Miller Fisher/imunologia , Couro Cabeludo/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
Anti-GQ1b antibodies can be detected in the serum of patients with Miller Fisher syndrome (MFS) and its incomplete forms such as acute ophthalmoparesis (AO), acute ptosis, acute mydriasis, acute oropharyngeal palsy and acute ataxic neuropathy (AAN), as well as in pharyngeal-cervical-brachial weakness, Bickerstaff brainstem encephalitis (BBE) and in overlap syndromes with Guillain-Barré syndrome (MFS-GBS, BBE-GBS). We searched the laboratory medicine database at University Hospitals Leuven between 2002 and 2017 for serum samples with anti-GQ1b IgG antibodies. We identified eight patients with anti-GQ1b antibodies: 4 MFS, 2 AO, 1 MFS-GBS and 1 AAN. Mean age was 57 years and five patients were males. Preceding illness was present in all patients. At nadir, we observed most frequently gait disturbance, external ophthalmoplegia and absent/decreased reflexes. Albumino-cytological dissociation was present in four patients. Mean time between onset and nadir was 4 days, between onset and recovery 2.5 months. Five patients recovered completely and three had minor residual symptoms. Interestingly, one patient with AO experienced a second identical episode, approximately 1 year after the first one. Our data confirm the broad clinical spectrum associated with the presence of anti-GQ1b IgG antibodies. Incomplete MFS subtypes such as AO are a challenge for diagnosis, because of the limited (though invalidating) clinical presentation and the lack of confirming ancillary tests. Subacute onset of ophthalmoplegia and/or ataxia should urge the clinician to include the anti-GQ1b antibody syndrome in the differential diagnosis.
Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Gangliosídeos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoantígenos/imunologia , Feminino , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/diagnóstico , Síndrome de Miller Fisher/imunologia , Oftalmoplegia/diagnóstico , Oftalmoplegia/imunologia , Paraplegia/diagnóstico , Paraplegia/imunologia , Síndrome , Adulto JovemAssuntos
Anticorpos/sangue , Gangliosídeo G(M3)/imunologia , Gangliosídeos/imunologia , Síndrome de Miller Fisher/sangue , Síndrome de Miller Fisher/imunologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Síndrome de Miller Fisher/fisiopatologia , Síndrome de Miller Fisher/terapia , Condução Nervosa/fisiologia , NeuraminidaseRESUMO
INTRODUCTION: Our aim was to study dengue-related immune-mediated neurological complications (IMNC) during the recent epidemic. MATERIALS AND METHODS: This was a cross-sectional observational study of 79 IMNC cases from 1627 laboratory confirmed dengue cases from January 2015 to January 2016 and their follow-up for 3 months. According to the World Health Organization, cases were categorized into those having dengue fever (DF), and those having a severe syndrome that includes dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Laboratory as well as clinicoradiological data, the predictors of outcome, and the role of immunomodulation in determining the final result were analyzed. RESULTS: Out of the 1627 confirmed dengue cases, 14.6% developed neurological complications and only 4.86% cases had IMNC. Among the IMNC seen, the majority of the patients had the onset of their manifestations in the subacute (7-30 days) latency period; however, there was no mortality seen. We found Miller Fisher syndrome (MFS), limbic encephalitis, and immune-mediated cerebellar demyelination (IMCD) as the new findings in the IMNC spectrum. Patients with DF were more prone to developing brachial plexus neuritis and polyneuritis cranialis, whereas those patients with a severe syndrome were more commonly associated with Guillain-Barre syndrome (GBS). Significant (P < 0.001) predictors of central nervous system involvement were anemia, an elevated hematocrit, and the presence of DSS, whereas patients with a higher mean body temperature, DF, and elevated hematocrit were more prone to developing peripheral nervous system manifestations. The platelets counts and the hemoglobin levels had a negative correlation whereas the hematocrit value, the mean body temperature, and the alanine aminotransferase levels had a moderately significant positive correlation for the development of IMNC. The immunomodulatory therapy (IMT), if initiated after fever abatement led to a significant clinically favorable outcome at 3 months, especially in patients with GBS, polyneuritis cranialis, and brachial plexus neuritis. CONCLUSION: The spectrum of IMNC is vast and may include MFS, limbic encephalitis and IMCD. Early initiation of IMT, in the presence of significant predictors, may reduce the IMNC-related morbidity.