RESUMEN
Acquired cerebellar ataxia is a rare, in many cases immune-modulated and paraneoplastic illness. Acute and slowly progredient processes are possible. An early treatment is important for a good clinical outcome. Here we present the case of female patient in her 60s with an antirecoverin associated cerebellitis without retinopathia and neoplasia. After an immunosuppressive therapy with steroids and rituximab the symptoms improved, and the progression could be stopped.
Asunto(s)
Autoanticuerpos/sangre , Ataxia Cerebelosa/diagnóstico , Ataxia de la Marcha/diagnóstico , Inmunosupresores/uso terapéutico , Recoverina/inmunología , Edad de Inicio , Autoanticuerpos/inmunología , Ataxia Cerebelosa/sangre , Ataxia Cerebelosa/tratamiento farmacológico , Ataxia Cerebelosa/inmunología , Cerebelo/diagnóstico por imagen , Cerebelo/inmunología , Tecnología de Seguimiento Ocular , Femenino , Ataxia de la Marcha/sangre , Ataxia de la Marcha/tratamiento farmacológico , Ataxia de la Marcha/inmunología , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Imagen por Resonancia Magnética , Persona de Mediana Edad , Rituximab/uso terapéuticoRESUMEN
BACKGROUND & AIMS: Celiac disease is an autoimmune disorder induced by ingestion of gluten that affects 1% of the population and is characterized by gastrointestinal symptoms, weight loss, and anemia. We evaluated the presence of neurologic deficits and investigated whether the presence of antibodies to Transglutaminase 6 (TG6) increases the risk of neurologic defects in patients with a new diagnosis of celiac disease. METHODS: We performed a prospective cohort study at a secondary-care gastroenterology center of 100 consecutive patients who received a new diagnosis of celiac disease based on gastroscopy and duodenal biopsy. We collected data on neurologic history, and patients were evaluated in a clinical examination along with magnetic resonance imaging of the brain, magnetic resonance (MR) spectroscopy of the cerebellum, and measurements of antibodies against TG6 in serum samples. The first 52 patients recruited underwent repeat MR spectroscopy at 1 year after a gluten-free diet (GFD). The primary aim was to establish if detection of antibodies against TG6 can be used to identify patients with celiac disease and neurologic dysfunction. RESULTS: Gait instability was reported in 24% of the patients, persisting sensory symptoms in 12%, and frequent headaches in 42%. Gait ataxia was found in 29% of patients, nystagmus in 11%, and distal sensory loss in 10%. Sixty percent of patients had abnormal results from magnetic resonance imaging, 47% had abnormal results from MR spectroscopy of the cerebellum, and 25% had brain white matter lesions beyond that expected for their age group. Antibodies against TG6 were detected in serum samples from 40% of patients-these patients had significant atrophy of subcortical brain regions compared with patients without TG6 autoantibodies. In patients with abnormal results from MR spectroscopy of the cerebellum, those on the GFD had improvements detected in the repeat MR spectroscopy 1 year later. CONCLUSIONS: In a prospective cohort study of patients with a new diagnosis of celiac disease at a gastroenterology clinic, neurologic deficits were common and 40% had circulating antibodies against TG6. We observed a significant reduction in volume of specific brain regions in patients with TG6 autoantibodies, providing evidence for a link between autoimmunity to TG6 and brain atrophy in patients with celiac disease. There is a need for early diagnosis, increased awareness of the neurologic manifestations among clinicians, and reinforcement of adherence to a strict GFD by patients to avoid permanent neurologic disability.
Asunto(s)
Autoanticuerpos/inmunología , Encéfalo/diagnóstico por imagen , Enfermedad Celíaca/inmunología , Ataxia de la Marcha/inmunología , Cefalea/inmunología , Enfermedades del Sistema Nervioso Periférico/inmunología , Transglutaminasas/inmunología , Sustancia Blanca/diagnóstico por imagen , Adulto , Anciano , Atrofia , Encéfalo/patología , Enfermedad Celíaca/diagnóstico por imagen , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/fisiopatología , Cerebelo/diagnóstico por imagen , Estudios de Cohortes , Dieta Sin Gluten , Femenino , Proteínas de Unión al GTP , Ataxia de la Marcha/diagnóstico por imagen , Ataxia de la Marcha/fisiopatología , Gliadina/inmunología , Antígenos HLA-DQ , Cefalea/diagnóstico por imagen , Cefalea/fisiopatología , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Nistagmo Patológico/inmunología , Nistagmo Patológico/fisiopatología , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Estudios Prospectivos , Proteína Glutamina Gamma Glutamiltransferasa 2 , Resultado del Tratamiento , Adulto JovenAsunto(s)
Afasia/inmunología , Autoanticuerpos/metabolismo , Demencia/inmunología , Ataxia de la Marcha/inmunología , Proteínas de la Membrana/inmunología , Proteínas del Tejido Nervioso/inmunología , Neoplasias de la Próstata/inmunología , Anciano , Afasia/tratamiento farmacológico , Encéfalo/fisiopatología , Demencia/diagnóstico , Demencia/tratamiento farmacológico , Diagnóstico Diferencial , Resultado Fatal , Ataxia de la Marcha/diagnóstico , Ataxia de la Marcha/tratamiento farmacológico , Humanos , Inmunoglobulina G/metabolismo , Masculino , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/psicología , SíndromeAsunto(s)
Autoanticuerpos/sangre , Enfermedades Autoinmunes/inmunología , Gangliósidos/inmunología , Inmunoglobulina M/sangre , Enfermedad de la Neurona Motora/inmunología , Conducción Nerviosa/fisiología , Neuritis/inmunología , Oftalmoplejía/inmunología , Parestesia/inmunología , Adulto , Anciano , Enfermedades Autoinmunes/diagnóstico , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Ataxia de la Marcha/diagnóstico , Ataxia de la Marcha/inmunología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/diagnóstico , Neuritis/diagnóstico , Examen Neurológico , Oftalmoplejía/diagnóstico , Parestesia/diagnósticoRESUMEN
Opsoclonus-myoclonus-ataxia syndrome (OMS) is a rare neurological disorder of probably autoimmune origin. Most cases are associated with a remote neoplasm or a viral infection; however in some instances no underlying aetiology can be demonstrated. We report the presence of anti-glutamic acid decarboxylase antibodies (anti-GAD Abs) in the serum and CSF of a patient with idiopathic OMS. Treatment with intravenous immunoglobulin led to a remarkable clinical improvement with parallel reduction of anti-GAD titers. Anti-GAD Abs have been associated with several neurological syndromes. They could also be responsible for the clinical triad of OMS, by impairing GABAergic transmission in specific brainstem and cerebellar circuits. We propose that testing for anti-GAD Abs should be performed in OMS, especially when no other aetiological association can be demonstrated.
Asunto(s)
Autoanticuerpos/análisis , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/inmunología , Ataxia de la Marcha/etiología , Ataxia de la Marcha/inmunología , Glutamato Descarboxilasa/inmunología , Mioclonía/etiología , Mioclonía/inmunología , Trastornos de la Motilidad Ocular/etiología , Trastornos de la Motilidad Ocular/inmunología , Adulto , Antiinflamatorios/uso terapéutico , Anticonvulsivantes/uso terapéutico , Autoanticuerpos/sangre , Autoanticuerpos/líquido cefalorraquídeo , Femenino , Ataxia de la Marcha/tratamiento farmacológico , Humanos , Metilprednisolona/uso terapéutico , Mioclonía/tratamiento farmacológico , Trastornos de la Motilidad Ocular/tratamiento farmacológico , Radioinmunoensayo , Síndrome , Ácido Valproico/uso terapéuticoRESUMEN
We describe the clinical course, with special attention to the disturbance of eye movements, of a 29-year-old man with chronic ataxic neuropathy with ophthalmoplegia, IgM paraprotein, cold agglutinins and anti-GD1b disialosyl antibodies (CANOMAD). Using the magnetic search coil technique, we documented convergence during upward saccades and other features suggestive of dorsal midbrain syndrome. Thus, in common with Miller Fisher syndrome, CANOMAD may present with clinical findings implicating involvement of the central nervous system, which contains ganglioside antigens to anti-GD1b antibodies.
Asunto(s)
Anemia Hemolítica Autoinmune/diagnóstico , Autoanticuerpos/sangre , Ataxia de la Marcha/diagnóstico , Gangliósidos/inmunología , Inmunoglobulina M/sangre , Mesencéfalo , Oftalmoplejía/diagnóstico , Paraproteinemias/diagnóstico , Adulto , Anemia Hemolítica Autoinmune/inmunología , Anemia Hemolítica Autoinmune/terapia , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Diagnóstico Diferencial , Ataxia de la Marcha/inmunología , Ataxia de la Marcha/terapia , Humanos , Masculino , Examen Neurológico , Oftalmoplejía/inmunología , Oftalmoplejía/terapia , Paraproteinemias/inmunología , Paraproteinemias/terapia , Intercambio Plasmático , Rituximab , SíndromeAsunto(s)
Autoanticuerpos/inmunología , Vaina de Mielina/inmunología , Glicoproteína Asociada a Mielina/inmunología , Polineuropatías/inmunología , Polirradiculoneuropatía/inmunología , Anciano , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales de Origen Murino , Autoanticuerpos/sangre , Evaluación de la Discapacidad , Ataxia de la Marcha/inmunología , Ataxia de la Marcha/fisiopatología , Humanos , Hipoestesia/inmunología , Hipoestesia/fisiopatología , Factores Inmunológicos/uso terapéutico , Pierna/inervación , Pierna/fisiopatología , Masculino , Vaina de Mielina/patología , Nervios Periféricos/inmunología , Nervios Periféricos/patología , Nervios Periféricos/fisiopatología , Polineuropatías/sangre , Polineuropatías/tratamiento farmacológico , Polirradiculoneuropatía/sangre , Polirradiculoneuropatía/tratamiento farmacológico , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/inmunología , Rituximab , Hermanos , Resultado del TratamientoRESUMEN
An elderly woman complaining of a gait disorder was found to have the GALOP syndrome (gait ataxia, late-onset polyneuropathy). She exhibited mild distal weakness and sensory loss in the legs, a positive Romberg, and an unsteady gait. Serum immunofixation disclosed a monoclonal IgM-kappa protein. There was specific IgM binding to galopin, a central nervous system white matter antigen. Periodic treatment with intravenous immunoglobulin has alleviated her neurologic symptoms. She has now been followed for 7 years and maintained significant improvement in neurologic symptoms and signs.
Asunto(s)
Ataxia de la Marcha/inmunología , Ataxia de la Marcha/terapia , Polineuropatías/inmunología , Polineuropatías/terapia , Edad de Inicio , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Ataxia de la Marcha/diagnóstico , Humanos , Polineuropatías/diagnóstico , SíndromeRESUMEN
We previously have described a group of patients with gluten sensitivity presenting with ataxia (gluten ataxia) and suggested that this disease entity may account for a large number of patients with sporadic idiopathic ataxia. We have therefore investigated the prevalence of gluten sensitivity amongst a large cohort of patients with sporadic and familial ataxia and looked at possible genetic predisposition to gluten sensitivity amongst these groups. Two hundred and twenty-four patients with various causes of ataxia from North Trent (59 familial and/or positive testing for spinocerebellar ataxias 1, 2, 3, 6 and 7, and Friedreich's ataxia, 132 sporadic idiopathic and 33 clinically probable cerebellar variant of multiple system atrophy MSA-C) and 44 patients with sporadic idiopathic ataxia from The Institute of Neurology, London, were screened for the presence of antigliadin antibodies. A total of 1200 volunteers were screened as normal controls. The prevalence of antigliadin antibodies in the familial group was eight out of 59 (14%), 54 out of 132 (41%) in the sporadic idiopathic group, five out of 33 (15%) in the MSA-C group and 149 out of 1200 (12%) in the normal controls. The prevalence in the sporadic idiopathic group from London was 14 out of 44 (32%). The difference in prevalence between the idiopathic sporadic groups and the other groups was highly significant (P < 0.0001 and P < 0.003, respectively). The clinical characteristics of 68 patients with gluten ataxia were as follows: the mean age at onset of the ataxia was 48 years (range 14-81 years) with a mean duration of the ataxia of 9.7 years (range 1-40 years). Ocular signs were observed in 84% and dysarthria in 66%. Upper limb ataxia was evident in 75%, lower limb ataxia in 90% and gait ataxia in 100% of patients. Gastrointestinal symptoms were present in only 13%. MRI revealed atrophy of the cerebellum in 79% and white matter hyperintensities in 19%. Forty-five percent of patients had neurophysiological evidence of a sensorimotor axonal neuropathy. Gluten-sensitive enteropathy was found in 24%. HLA DQ2 was present in 72% of patients. Gluten ataxia is therefore the single most common cause of sporadic idiopathic ataxia. Antigliadin antibody testing is essential at first presentation of patients with sporadic ataxia.
Asunto(s)
Ataxia/complicaciones , Enfermedad Celíaca/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos/análisis , Ataxia/inmunología , Ataxia/patología , Estudios de Casos y Controles , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/patología , Ataxia Cerebelosa/complicaciones , Ataxia Cerebelosa/inmunología , Ataxia Cerebelosa/patología , Cerebelo/patología , Femenino , Ataxia de Friedreich/complicaciones , Ataxia de Friedreich/inmunología , Ataxia de Friedreich/patología , Ataxia de la Marcha/complicaciones , Ataxia de la Marcha/inmunología , Ataxia de la Marcha/patología , Predisposición Genética a la Enfermedad , Gliadina/inmunología , Antígenos HLA-DQ/análisis , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
A middle-aged patient presented with subacute muscular stiffness, myocloni of both extremity and facial muscles, gait ataxia and symmetrical distal painful paraesthesias. Electrophysiologically, neuromyotonia was confirmed. High titer anti-Hu antibodies were detected, but no other paraneoplastic antibodies were found. Small-cell lung cancer was diagnosed. Under chemotherapy tumor remission was achieved and, except for minor sensory deficits, neurological symptoms disappeared. This report shows that paraneoplastic syndromes associated with antibodies to neuronal nucleoproteins (anti-Hu antibodies) may be associated with a syndrome including neuromyotonia, sensory neuropathy, cerebellar symptoms and myocloni.