RESUMEN
BACKGROUND: In around 20% of cases, myelin oligodendrocyte glycoprotein (MOG) immunoglobulin (IgG)-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) first occurs in a postinfectious or postvaccinal setting. OBJECTIVE: To report a case of MOG-EM with onset after vaccination with the Pfizer BioNTech COVID-19 mRNA vaccine BNT162b2 (Comirnaty®) and to provide a comprehensive review of the epidemiological, clinical, radiological, electrophysiological and laboratory features as well as treatment outcomes of all published patients with SARS-CoV-2 vaccination-associated new-onset MOG-EM. METHODS: Case report and review of the literature. RESULTS: In our patient, MOG-IgG-positive (serum 1:1000, mainly IgG1 and IgG2; CSF 1:2; MOG-specific antibody index < 4) unilateral optic neuritis (ON) occurred 10 days after booster vaccination with BNT162b2, which had been preceded by two immunizations with the vector-based Oxford AstraZeneca vaccine ChAdOx1-S/ChAdOx1-nCoV-19 (AZD1222). High-dose steroid treatment with oral tapering resulted in complete recovery. Overall, 20 cases of SARS-CoV2 vaccination-associated MOG-EM were analysed (median age at onset 43.5 years, range 28-68; female to male ratio = 1:1.2). All cases occurred in adults and almost all after immunization with ChAdOx1-S/ChAdOx1 nCoV-19 (median interval 13 days, range 7-32), mostly after the first dose. In 70% of patients, more than one CNS region (spinal cord, brainstem, supratentorial brain, optic nerve) was affected at onset, in contrast to a much lower rate in conventional MOG-EM in adults, in which isolated ON is predominant at onset and ADEM-like phenotypes are rare. The cerebrospinal fluid white cell count (WCC) exceeded 100 cells/µl in 5/14 (36%) patients with available data (median peak WCC 58 cells/µl in those with pleocytosis; range 6-720). Severe disease with tetraparesis, paraplegia, functional blindness, brainstem involvement and/or bladder/bowel dysfunction and a high lesion load was common, and treatment escalation with plasma exchange (N = 9) and/or prolonged IVMP therapy was required in 50% of cases. Complete or partial recovery was achieved in the majority of patients, but residual symptoms were significant in some. MOG-IgG remained detectable in 7/7 cases after 3 or 6 months. CONCLUSIONS: MOG-EM with postvaccinal onset was mostly observed after vaccination with ChAdOx1-S/ChAdOx1 nCoV-19. Attack severity was often high at onset. Escalation of immunotherapy was frequently required. MOG-IgG persisted in the long term.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Encefalomielitis , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica , Autoanticuerpos , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , ChAdOx1 nCoV-19 , Encefalomielitis/etiología , Femenino , Humanos , Inmunoglobulina G , Masculino , ARN Viral , SARS-CoV-2 , Vacunación/efectos adversos , Vacunas Sintéticas , Vacunas de ARNmRESUMEN
We describe a 13-years-old girl, previously diagnosed with PTPN11-associated Noonan Syndrome (NS), who presented to the pediatric emergency department for fever and drowsiness, which gradually worsened within 48 h. On admission, brain magnetic resonance imaging (MRI) scan showed diffuse, symmetric, multiple, poorly demarcated, confluent hyperintense lesions on MRI T2w-images, located in the Central Nervous System (CNS). In the absence of a better explanation and according to the current diagnostic criteria, a diagnosis of Acute Disseminated Encephalomyelitis (ADEM) was performed. The patient was first treated with intravenous methylprednisolone, then with intravenous immunoglobulin (IVIG). Owing to the poor clinical response, three sessions of therapeutic plasma exchange (TPE) were finally performed, with a progressive improvement. Follow-up MRI performed after three months from the onset revealed a considerable reduction in brain lesions, while cervical and dorsal ones were substantially unmodified. Neurological examination showed a full recovery of cognitive function and improved strength and tone of the upper limbs, while tetrahyporeflexia and proximal weakness of lower limbs were still appreciable. To date, this is the first described case of ADEM occurring in a patient with NS.
Asunto(s)
Encefalomielitis/etiología , Síndrome de Noonan/complicaciones , Adolescente , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Encefalomielitis/complicaciones , Encefalomielitis/patología , Encefalomielitis/terapia , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Metilprednisolona/uso terapéutico , Síndrome de Noonan/genética , Síndrome de Noonan/patología , Intercambio PlasmáticoRESUMEN
Neurologic complications are being recognized as important outcomes of coronavirus disease 2019 (COVID-19). Pathogenesis is varied and incompletely understood, and may include neuroinvasion, indirect post-infectious neuroinflammation, and cerebrovascular pathologies. We present a case of COVID-19-related encephalomyeloradiculitis with clinical and magnetic resonance imaging characteristics of neuromyelitis optica spectrum disorders that was associated with anti-aquaporin-4 antibodies. Our case suggests post-infectious autoimmunity as a mechanism in at least a subset of patients with COVID-19-related neurologic disease.
Asunto(s)
Acuaporina 4/inmunología , Autoanticuerpos/análisis , Enfermedades Autoinmunes/etiología , COVID-19/complicaciones , Encefalomielitis/etiología , Radiculopatía/etiología , Azatioprina/uso terapéutico , Encéfalo/diagnóstico por imagen , COVID-19/diagnóstico por imagen , Encefalomielitis/diagnóstico por imagen , Encefalomielitis/inmunología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/etiología , Intercambio Plasmático , Radiculopatía/diagnóstico por imagen , Radiculopatía/inmunología , Columna Vertebral/diagnóstico por imagenRESUMEN
Complications involving the central nervous system (CNS) occur in 9-14% of patients following allogeneic hematopoietic stem cell transplantation (HSCT), including stroke-like episodes, demyelination, encephalitis, and nonspecific neurological symptoms. Here we report a case of multiple sclerosis (MS) like relapsing remitting encephalomyelitis following allogeneic HSCT, which did not respond to disease modifying therapies (DMTs) and "domino" autologous HSCT. A 53-year-old male was treated with allogeneic HSCT for lymphoid blast transformation of chronic myeloid leukemia. Ten months later he presented with confusion, slurred speech, left sided facial weakness and ataxia. A magnetic resonance imaging brain scan showed multiple enhancing tumefactive lesions. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein (MOG) antibodies were negative. After extensive investigations for infections, autoimmune disorders and recurrence of malignancy, he underwent brain biopsy, which showed a macrophage rich lesion with severe myelin loss but axonal preservation indicating a demyelinating pathology. Although his symptoms improved with corticosteroids, he relapsed five months later. In the absence of any systemic features suggesting graft versus host disease (GvHD), his presentation was thought to be compatible with MS. The illness followed an aggressive course that did not respond to glatiramer acetate and natalizumab. He was therefore treated with "domino" autologous HSCT, which also failed to induce long-term remission. Despite further treatment with ocrelizumab, he died of progressive disease. An autopsy limited to the examination of brain revealed multifocal destructive leukoencephalopathy with severe myelin and axonal loss. Immunohistochemistry showed macrophage located in the perivascular area, with no T or B lymphocytes. The appearance was unusual and not typical for chronic MS plaques. Reported cases of CNS demyelination following allogeneic HSCT are very limited in the literature, especially in relation to histopathological examination. Although the clinical disease course of our patient following allogeneic HSCT resembled an "MS-like" relapsing remitting encephalomyelitis, the autopsy examination did not show any evidence of active inflammation. The impact of DMTs and HSCT on the histological appearance of "MS-like" CNS pathologies is unknown. Therefore, reporting this and similar cases will improve our awareness and understanding of underlying disease mechanisms.
Asunto(s)
Encefalomielitis/etiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/cirugía , Esclerosis Múltiple Recurrente-Remitente/etiología , Corticoesteroides/uso terapéutico , Progresión de la Enfermedad , Encefalomielitis/tratamiento farmacológico , Resultado Fatal , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Humanos , Factores Inmunológicos/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Activación de Linfocitos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Recurrencia , Trasplante Autólogo/efectos adversos , Trasplante Homólogo/efectos adversosRESUMEN
A 4-week-old male neonate with a history of intermittent hypothermia in the newborn nursery presented with an acute onset of bilateral lower extremity paralysis and areflexia. Extensive workup demonstrated eosinophilic encephalomyelitis and multifocal hemorrhages of the brain and spinal cord. Funduscopic examination revealed bilateral chorioretinitis with macular scarring. The laboratory values were notable for peripheral eosinophilia and cerebrospinal fluid eosinophilic pleocytosis (28 white blood cells/µL, 28% eosinophils), markedly elevated protein (1214 mg/dL), and hypoglycorrhachia (20 mg/dL). Toxoplasma gondii immunoglobulin M (IgM) test result was positive. Reference testing obtained at the Palo Alto Medical Foundation Toxoplasma Serology Laboratory confirmed the diagnosis of congenital toxoplasmosis in the infant with a positive immunoglobulin G (IgG) dye test result, immunoglobulin A enzyme-linked immunosorbent assay, and IgM immunosorbent agglutination assay. The diagnosis of an infection acquired during gestation in the mother was established by a positive maternal IgG dye test result, IgM enzyme-linked immunosorbent assay, immunoglobulin A, immunoglobulin E, and low IgG avidity. At 6-month follow-up, the infant had marginal improvement in his retinal lesions and residual paraplegia with hyperreflexia and clonus of the lower extremities. A repeat MRI demonstrated interval development of encephalomalacia with suspected cortical laminar necrosis and spinal cord atrophy in the areas of previous hemorrhage. Clinicians should be aware of this severe spectrum of congenital toxoplasmosis disease and should remain vigilant for subtler signs that may prompt earlier testing, diagnosis, and treatment.
Asunto(s)
Encefalomielitis/etiología , Eosinofilia/complicaciones , Hemorragia/etiología , Enfermedades de la Médula Espinal/etiología , Toxoplasmosis Congénita/complicaciones , Anticuerpos Antiprotozoarios/sangre , Encefalomielitis/diagnóstico por imagen , Encefalomielitis/parasitología , Hemorragia/diagnóstico por imagen , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Enfermedades de la Médula Espinal/diagnóstico por imagen , Toxoplasma/inmunología , Toxoplasmosis Congénita/diagnóstico por imagenRESUMEN
We present a case of a 65-year-old African American male, immunosuppressed on Tacrolimus, who initially presented with cerebellar ataxia and rapidly developed Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) with positive anti-glutamic acid decarboxylase (GAD65) antibodies, no underlying malignancy, and normal neuroimaging. PERM is a rare spectrum of Stiff Person Syndrome (SPS), which is strongly associated with anti-GAD antibodies and characterized by flare-ups and remissions of encephalopathy, myelopathy and rigidity with myoclonus. PERM is diagnosed clinically and has been successfully treated with both Intravenous Immunoglobulin (IVIg) and plasmapheresis. Our patient was successfully treated with IVIg. On day 14 after starting IVIg treatment, his neurological symptoms started to improve and ultimately returned to baseline.
Asunto(s)
Autoanticuerpos/inmunología , Autoantígenos/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/etiología , Ataxia Cerebelosa/complicaciones , Encefalomielitis/etiología , Glutamato Descarboxilasa/inmunología , Inmunoglobulinas Intravenosas/uso terapéutico , Rigidez Muscular/etiología , Síndrome de la Persona Rígida/etiología , Anciano , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/terapia , Ataxia Cerebelosa/inmunología , Encefalomielitis/inmunología , Encefalomielitis/terapia , Humanos , Huésped Inmunocomprometido , Inmunoterapia , Trasplante de Riñón , Masculino , Rigidez Muscular/inmunología , Rigidez Muscular/terapia , Plasmaféresis , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/inmunología , Complicaciones Posoperatorias/terapia , Inducción de Remisión , Síndrome de la Persona Rígida/inmunología , Síndrome de la Persona Rígida/terapiaRESUMEN
A 33-year-old man was admitted to our hospital with bilateral facial nerve paralysis, dysphagia, and muscle weakness in the neck and trunk following fever, headache and throat pain. T2-weighted brain magnetic resonance imaging (MRI) showed hyperintense lesions in the tegmentum of the brain stem and the ventral region of the superior cervical cord. Based on the characteristic findings on the brain MRI, we diagnosed the patient with enteroviral encephalomyelitis. Steroid therapy was administered; however, his bilateral facial nerve paralysis and dysphagia were refractory to this therapy. Subsequently, enterovirus D68 was detected in the serum using polymerase chain reaction (PCR) analysis. At that time, an outbreak of enteroviral D68 infection was reported in Japan. Finally, we diagnosed encephalomyelitis caused by enteroviral D68 infection. Characteristic MRI findings were very useful in narrowing down the differential diagnosis in this patient. (Received March 3, 2017; Accepted April 20, 2017; Published August 1, 2017).
Asunto(s)
Trastornos de Deglución/etiología , Encefalomielitis/etiología , Infecciones por Enterovirus/complicaciones , Nervio Facial , Parálisis Facial/etiología , Adulto , Humanos , MasculinoRESUMEN
The most serious complications of the central nervous system that occur after venomous snake bite are intracranial hemorrhage and ischemic stroke.We present a rarely seen central nervous system complication, acute demyelinating encephalomyelitis, after a treated Deinagkistrodon's viper bite.On April 5, 2015, a 50-year-old male farmer was bitten on his right leg by a Deinagkistrodon's viper. The bite rendered the victim unconscious for 14 days, during which he was treated with tetanus toxoid and polyvalent antisnake venom. Acute demyelinating encephalomyelitis (ADEM) was suspected after magnetic resonance imaging of the brain. After a high dose of methylprednisolone was used as diagnostic treatment, the patient started recovering fast.ADEM is a rare complication after snake bite, and is triggered by venom or antivenin. Magnetic resonance imaging helps in the early diagnosis of ADEM, and high-dose corticosteroid therapy appears to be effective in ADEM after viper bite or antivenin management.
Asunto(s)
Enfermedades Desmielinizantes/etiología , Encefalomielitis/etiología , Mordeduras de Serpientes/complicaciones , Viperidae , Enfermedad Aguda , Animales , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Within the last decade, autoantibody-associated encephalitis and encephalomyelitis have stepped into the focus of clinical research and practice. Besides the "classic" autoantibodies against intracellular neuronal antigenes, a growing number of antibodies directed against pre- and postsynaptic surface proteins of neurons have been described since the millennium change. Whereas the "classic" are closely linked to paraneoplastic syndromes, this association is loose for most of the yet known surface antigen-antibodies. The immune-mediated encephalomyelitic syndromes are thus classified not only by their clinical symptoms, but also by their specific antibodies. The definition of the entity of N-methyl-D-aspartate-receptor encephalitis is a prominent example. The presented work gives an overview on the clinical and pathological correlates and the underlying immunologic processes of autoantibody-associated encephalitis from a neuropsychiatric perspective.
Asunto(s)
Enfermedades Autoinmunes/complicaciones , Encefalomielitis/etiología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Encefalomielitis/inmunología , HumanosRESUMEN
IMPORTANCE: Enterovirus 71 (EV71) causes a spectrum of neurological complications with significant morbidity and mortality. Further understanding of the characteristics of EV71-related neurological disease, factors related to outcome, and potential responsiveness to treatments is important in developing therapeutic guidelines. OBJECTIVE: To further characterize EV71-related neurological disease and neurological outcome in children. DESIGN, SETTING, AND PARTICIPANTS: Prospective 2-hospital (The Sydney Children's Hospitals Network) inpatient study of 61 children with enterovirus-related neurological disease during a 2013 outbreak of EV71 in Sydney, Australia. The dates of our analysis were January 1, to June 30, 2013. MAIN OUTCOMES AND MEASURES: Clinical, neuroimaging, laboratory, and pathological characteristics, together with treatment administered and functional motor outcomes, were assessed. RESULTS: Among 61 patients, there were 4 precipitous deaths (7%), despite resuscitation at presentation. Among 57 surviving patients, the age range was 0.3 to 5.2 years (median age, 1.5 years), and 36 (63%) were male. Fever (100% [57 of 57]), myoclonic jerks (86% [49 of 57]), ataxia (54% [29 of 54]), and vomiting (54% [29 of 54]) were common initial clinical manifestations. In 57 surviving patients, EV71 neurological disease included encephalomyelitis in 23 (40%), brainstem encephalitis in 20 (35%), encephalitis in 6 (11%), acute flaccid paralysis in 4 (7%), and autonomic dysregulation with pulmonary edema in 4 (7%). Enterovirus RNA was more commonly identified in feces (42 of 44 [95%]), rectal swabs (35 of 37 [95%]), and throat swabs (33 of 39 [85%]) rather than in cerebrospinal fluid (10 of 41 [24%]). Magnetic resonance imaging revealed characteristic increased T2-weighted signal in the dorsal pons and spinal cord. All 4 patients with pulmonary edema (severe disease) demonstrated dorsal brainstem restricted diffusion (odds ratio, 2; 95% CI, 1-4; P = .001). Brainstem or motor dysfunction had resolved in 44 of 57 (77%) at 2 months and in 51 of 57 (90%) at 12 months. Focal paresis was evident in 23 of 57 (40%) at presentation and was the most common persisting clinical and functional problem at 12 months (observed in 5 of 6 patients), with 1 patient also requiring invasive ventilation. Patients initially seen with acute flaccid paralysis or pulmonary edema had significantly greater frequencies of motor dysfunction at follow-up compared with patients initially seen with other syndromes (odds ratio, 15; 95% CI, 3-79; P < .001). CONCLUSIONS AND RELEVANCE: Enterovirus 71 may cause serious neurological disease in young patients. The distinct clinicoradiological syndromes, predominantly within the spinal cord and brainstem, enable rapid recognition within evolving outbreaks. Long-term functional neurological morbidity is associated with paresis linked to involvement of gray matter in the brainstem or spinal cord.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades Virales del Sistema Nervioso Central/etiología , Enterovirus Humano A/patogenicidad , Infecciones por Enterovirus/complicaciones , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Enfermedades Virales del Sistema Nervioso Central/diagnóstico , Enfermedades Virales del Sistema Nervioso Central/epidemiología , Preescolar , Encefalitis Viral/diagnóstico , Encefalitis Viral/epidemiología , Encefalitis Viral/etiología , Encefalomielitis/diagnóstico , Encefalomielitis/epidemiología , Encefalomielitis/etiología , Enterovirus Humano A/aislamiento & purificación , Infecciones por Enterovirus/diagnóstico , Infecciones por Enterovirus/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Imagen por Resonancia Magnética , Masculino , Nueva Gales del Sur/epidemiología , Parálisis/diagnóstico , Parálisis/epidemiología , Parálisis/etiologíaAsunto(s)
Enfermedades Desmielinizantes/diagnóstico , Enfermedades Desmielinizantes/etiología , Encefalomielitis/diagnóstico , Encefalomielitis/etiología , Infecciones por Mycoplasma/complicaciones , Infecciones por Mycoplasma/diagnóstico , Enfermedad Aguda , Antiinflamatorios/uso terapéutico , Encéfalo/patología , Preescolar , Enfermedades Desmielinizantes/tratamiento farmacológico , Diagnóstico Diferencial , Electroencefalografía , Encefalomielitis/terapia , Humanos , Inmunoglobulinas/uso terapéutico , Imagen por Resonancia Magnética , Masculino , Metilprednisolona/uso terapéutico , Infecciones por Mycoplasma/terapia , PlasmaféresisRESUMEN
UNLABELLED: Two distinct and potentially deceitful cases of neurologic melioidosis are reported. Case 1: A 39-year-old alcoholic and uncontrolled diabetic male presented with cough, fever, and left focal seizures with secondary generalization. An magnetic resonance imaging (MRI) brain scan revealed a small peripherally enhancing subdural collection along the interhemispheric fissure suggestive of minimal subdural empyema. Blood culture grew Burkholderia pseudomallei. Patient was diagnosed with disseminated bacteraemic melioidosis with subdural empyema. He was successfully treated with ceftazidime-cotrimoxazole-doxycycline. Case 2: A 45-year-old male presented with left lower limb weakness, difficulty in passing urine and stool, and back pain radiating to lower limbs. Neurological examination revealed flaccid left lower limb with absent deep tendon reflexes and plantar reflex. Spinal MRI showed T2 hyperintensity from D9 to L1 suggestive of demyelination. Patient was treated with high dose methylprednisolone. By day 3 of steroid treatment, lower limb weakness progressed. Subsequent MRI showed extensive cord hyperintensity on T2 weighted sequence extending from C5 to conus medullaris consistent with demyelination. Cerebrospinal fluid (CSF) culture grew B. pseudomallei, and the patient was given meropenem-cotrimoxazole. After three weeks of parenteral treatment, the lower limbs remained paralyzed. Patient was discharged on oral cotrimoxazole-doxycycline. CONCLUSIONS: Melioidosis should be considered as a differential in focal suppurative central nervous system (CNS) lesions, meningoencephalitis, or encephalomyelitis in endemic areas. CNS infections must be ruled out prior to steroid administration. The role of corticosteroids in demyelinating CNS melioidosis has been refuted. This is a rare documentation of effect of unintentional corticosteroid treatment in melioidosis.
Asunto(s)
Burkholderia pseudomallei/aislamiento & purificación , Empiema Subdural/etiología , Empiema Subdural/patología , Encefalomielitis/etiología , Encefalomielitis/patología , Melioidosis/diagnóstico , Melioidosis/patología , Adulto , Animales , Antibacterianos/uso terapéutico , Antiinflamatorios/uso terapéutico , Sangre/microbiología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/tratamiento farmacológico , Complicaciones de la Diabetes/patología , Empiema Subdural/complicaciones , Empiema Subdural/tratamiento farmacológico , Encefalomielitis/complicaciones , Encefalomielitis/tratamiento farmacológico , Humanos , India , Imagen por Resonancia Magnética , Masculino , Melioidosis/tratamiento farmacológico , Persona de Mediana Edad , Radiografía , Médula Espinal/diagnóstico por imagen , Médula Espinal/patologíaRESUMEN
Although CD8 T cells are key players in neuroinflammation, little is known about their trafficking cues into the central nervous system (CNS). We used a murine model of CNS autoimmunity to define the molecules involved in cytotoxic CD8 T-cell migration into the CNS. Using a panel of mAbs, we here show that the α4ß1-integrin is essential for CD8 T-cell interaction with CNS endothelium. We also investigated which α4ß1-integrin ligands expressed by endothelial cells are implicated. The blockade of VCAM-1 did not protect against autoimmune encephalomyelitis, and only partly decreased the CD8(+) T-cell infiltration into the CNS. In addition, inhibition of junctional adhesion molecule-B expressed by CNS endothelial cells also decreases CD8 T-cell infiltration. CD8 T cells may use additional and possibly unidentified adhesion molecules to gain access to the CNS.
Asunto(s)
Encéfalo/inmunología , Linfocitos T CD8-positivos/fisiología , Movimiento Celular , Encefalomielitis/etiología , Integrina alfa4beta1/fisiología , Animales , Encéfalo/citología , Linfocitos T CD8-positivos/citología , Moléculas de Adhesión Celular/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Microglía/fisiología , Molécula 1 de Adhesión Celular Vascular/fisiologíaRESUMEN
A 62-year-old woman with one-year history of type 1 diabetes mellitus was admitted to our hospital with progressive weakness in the lower extremities and urinary dysfunction following high fever. On admission, she had rigidity and myoclonus in the upper extremities with sensory ataxia. Cerebrospinal fluid examination revealed mild pleocytosis and oligoclonal band. Glutamic acid decarboxylase (GAD) antibodies were detected at high titer in serum, but antibodies to glycine receptor (GlyR), thyroid peroxidase, mitochondrial M2, and GM1 were also detected. She was diagnosed with progressive encephalomyelitis with rigidity and myoclonus (PERM), which probably developed on the basis of polyglandular autoimmune syndromes. The clinical symptoms began to improve after initiation of intravenous high-dose methylprednisolone. Muscle weakness might be related to GM1 antibodies. This is the first report of PERM, in which GM1 antibodies were detected with GAD and GlyR antibodies.
Asunto(s)
Autoanticuerpos/sangre , Encefalomielitis/etiología , Encefalomielitis/inmunología , Gangliósido G(M1)/inmunología , Glutamato Descarboxilasa/inmunología , Rigidez Muscular/etiología , Rigidez Muscular/inmunología , Mioclonía/etiología , Poliendocrinopatías Autoinmunes/complicaciones , Poliendocrinopatías Autoinmunes/inmunología , Receptores de Glicina/inmunología , Biomarcadores/sangre , Encefalomielitis/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Rigidez Muscular/diagnóstico , Poliendocrinopatías Autoinmunes/diagnósticoRESUMEN
Varicella zoster virus (VZV) causes the primary infection manifesting as varicella or chickenpox, with possibility of reactivation later in life. A 71-year-old man presented with headache and lower extremity weakness. There was no evidence of skin lesions to suggest a recent zoster infection. The patient had a history of multiple myeloma diagnosed 2 years earlier, treated with chemotherapy and autologous stem cell transplant. Antimicrobial prophylaxis was discontinued 12 months after the transplant. MRI of the brain demonstrated areas of T2/fluid-attenuated inversion recovery hyperintensity in bilateral cerebral white matter and MRI of the spine demonstrated enhancement along the cauda equine. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis and VZV DNA was detected by PCR in the CSF. The patient was treated with 8 weeks of antiviral therapy with complete resolution of symptoms. VZV should be considered in patients with haematopoietic stem cell transplantation presenting with similar neurological manifestations even in the absence of dermatological signs.
Asunto(s)
Encéfalo/virología , Varicela/diagnóstico , Encefalitis por Varicela Zóster/diagnóstico , Encefalomielitis/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Herpes Zóster/diagnóstico , Herpesvirus Humano 3 , Anciano , Antivirales/uso terapéutico , Varicela/líquido cefalorraquídeo , Varicela/etiología , Varicela/virología , ADN Viral , Encefalitis por Varicela Zóster/líquido cefalorraquídeo , Encefalitis por Varicela Zóster/etiología , Encefalitis por Varicela Zóster/virología , Encefalomielitis/líquido cefalorraquídeo , Encefalomielitis/etiología , Encefalomielitis/virología , Herpes Zóster/líquido cefalorraquídeo , Herpes Zóster/etiología , Herpes Zóster/virología , Herpesvirus Humano 3/genética , Humanos , Linfocitosis/líquido cefalorraquídeo , Masculino , Reacción en Cadena de la Polimerasa , Piel , Activación ViralRESUMEN
Amphiphysin antibody causes paraneoplastic stiff-person syndrome and can also result in a variety of neurological manifestations. Here, we investigated the clinical spectrum of 20 patients with non-stiff anti-amphiphysin syndrome and their responses to immunotherapy. The most common neurological manifestation was limbic encephalitis (n=10), followed by dysautonomia (n=9), and cerebellar dysfunction (n=6). Cancer was detected in only seven patients. Intravenous immunoglobulin or steroid treatment was effective in most patients, but three improved only after rituximab treatment. Our study suggests that anti-amphiphysin syndrome can manifest as non-stiff encephalomyelitis and is only partially associated with cancer. Active immunotherapy, including rituximab, would be beneficial.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Encefalitis Límbica/tratamiento farmacológico , Encefalitis Límbica/inmunología , Proteínas del Tejido Nervioso/inmunología , Síndrome de la Persona Rígida/tratamiento farmacológico , Síndrome de la Persona Rígida/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Enfermedades Cerebelosas/tratamiento farmacológico , Enfermedades Cerebelosas/etiología , Enfermedades Cerebelosas/inmunología , Encefalomielitis/tratamiento farmacológico , Encefalomielitis/etiología , Encefalomielitis/inmunología , Femenino , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Encefalitis Límbica/etiología , Masculino , Persona de Mediana Edad , Neoplasias/complicaciones , Disautonomías Primarias/tratamiento farmacológico , Disautonomías Primarias/etiología , Disautonomías Primarias/inmunología , Rituximab , Síndrome de la Persona Rígida/etiología , Resultado del TratamientoRESUMEN
Infection of the CNS (central nervous system) with a sublethal neurotropic coronavirus (JHMV) induces a vigorous inflammatory response. CD4⺠and CD8⺠T cells are essential to control infectious virus but at the cost of tissue damage. An enigma in understanding the contribution of T cell subsets in pathogenesis resides in their distinct migration pattern across the BBB (blood brain barrier). CD4⺠T cells transiently accumulate within the perivascular space, whereas CD8⺠T cells migrate directly into the CNS parenchyma. As MMPs (matrix metalloproteinases) facilitate migration across the glia limitans, specific expression of the TIMP (tissue inhibitor of MMPs)-1 by CD4⺠T cells present in the perivascular cuffs suggested that TIMP-1 is responsible for stalling CD4⺠T cell migration into the CNS parenchyma. Using TIMP-1 deficient mice, the present data demonstrate an increase rather than a decrease in CD4⺠T cell accumulation within the perivascular space during JHMV infection. Whereas virus control was not affected by perivascular retention of CD4⺠T cells, disease severity was decreased and associated with reduced IFNγ (interferon γ) production. Moreover, decreased CD4⺠T cell recruitment into the CNS parenchyma of TIMP-1 deficient mice was not associated with impaired T cell recruiting chemokines or MMP expression, and no compensation by other TIMP molecules was identified. These data suggest an MMP-independent role of TIMP-1 in regulating CD4⺠T cell access into the CNS parenchyma during acute JHMV encephalitis.
Asunto(s)
Barrera Hematoencefálica/metabolismo , Encefalomielitis/patología , Encefalomielitis/virología , Metaloproteinasas de la Matriz/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/deficiencia , Análisis de Varianza , Animales , Antígenos CD/metabolismo , Barrera Hematoencefálica/fisiopatología , Barrera Hematoencefálica/virología , Encéfalo/patología , Encéfalo/virología , Quimiocina CCL5/metabolismo , Quimiocina CXCL10/metabolismo , Coronavirus/fisiología , Infecciones por Coronavirus/complicaciones , Modelos Animales de Enfermedad , Encefalomielitis/etiología , Citometría de Flujo , Regulación Viral de la Expresión Génica/genética , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , ARN Mensajero/metabolismo , Inhibidor Tisular de Metaloproteinasa-1/genéticaRESUMEN
Traumatic brain injury (TBI) is a leading cause of mortality and disability. Acute postinjury insults after TBI, such as hypoxia, contribute to secondary brain injury and worse clinical outcomes. The functional and neuroinflammatory effects of brief episodes of hypoxia experienced following TBI have not been evaluated. Our previous studies have identified interleukin 6 (IL-6) as a potential mediator of mild TBI-induced pathology. In the present study, we sought to determine the effects of brief hypoxia on mild TBI and whether IL-6 played a role in the neuroinflammatory and functional deficits after injury. A murine model of mild TBI was induced by a weight drop (500 g from 1.5 cm). After injury, mice were exposed to immediate hypoxia (FIO2 = 15.1%) or normoxia (FIO2 = 21%) for 30 min. Serum and brain samples were analyzed for inflammatory cytokines 24 h after TBI. Neuron-specific enolase was measured as a serum biomarker of brain injury. Evaluation of motor coordination was performed for 5 days after TBI using a rotarod device. In some animals, anti-IL-6 was administered following TBI and hypoxia to neutralize systemic IL-6. Mice undergoing TBI had significant increases in brain injury. Exposure to brief hypoxia after TBI resulted in a more than 5-fold increase in serum neuron-specific enolase. This increase was associated with increases in serum and brain cytokine expression, suggesting that brief hypoxia exacerbates systemic and brain inflammation. Neutralization of IL-6 suppressed postinjury neuroinflammation and neuronal injury. In addition, TBI and hypoxia induced significant motor coordination deficits that were completely abrogated by IL-6 blockade. Exposure to hypoxia after TBI induces neuroinflammation and brain injury. These changes can be mitigated by neutralization of systemic IL-6. Interleukin 6 blockade also corrected the TBI-induced deficit in motor coordination. These data suggest that systemic IL-6 modulates the degree of neuroinflammation and contributes to reduced motor coordination after mild TBI.