Subject(s)
Autoantibodies/immunology , Cerebellar Ataxia/immunology , Glutamate Decarboxylase/immunology , Nystagmus, Pathologic/immunology , Aged , Azathioprine/therapeutic use , Cerebellar Ataxia/drug therapy , Diagnosis, Differential , Diplopia , Female , Humans , Immunosuppressive Agents/therapeutic use , Nystagmus, Pathologic/drug therapy , Steroids/therapeutic use , West IndiesABSTRACT
METHODS: This retrospective and descriptive study evaluated the clinical characteristics and outcomes of patients with CA-GAD-ab. RESULT: Three patients with cerebellar ataxia, high GAD-ab titers and autoimmune endocrine disease were identified. Patients 1 and 2 had classic stiff person syndrome and insidious-onset cerebellar ataxia, while Patient 3 had pure cerebellar ataxia with subacute onset. Patients received intravenous immunoglobulin therapy with no response in Patients 1 and 3 and partial recovery in Patient 2. CONCLUSION: CA-GAD-ab is rare and its clinical presentation may hamper diagnosis. Clinicians should be able to recognize this potentially treatable autoimmune cerebellar ataxia.
Subject(s)
Autoantibodies/blood , Cerebellar Ataxia/complications , Glutamate Decarboxylase/blood , Adult , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/drug therapy , Cerebellar Ataxia/immunology , Female , Glutamate Decarboxylase/immunology , Humans , Immunoglobulins, Intravenous/therapeutic use , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
ABSTRACT The enzyme glutamic acid decarboxylase (GAD), present in GABAergic neurons and in pancreatic beta cells, catalyzes the conversion of gamma-aminobutyric acid (GABA). The cerebellum is highly susceptible to immune-mediated mechanisms, with the potentially treatable autoimmune cerebellar ataxia associated with the GAD antibody (CA-GAD-ab) being a rare, albeit increasingly detected condition. Few cases of CA-GAD-ab have been described. Methods This retrospective and descriptive study evaluated the clinical characteristics and outcomes of patients with CA-GAD-ab. Result Three patients with cerebellar ataxia, high GAD-ab titers and autoimmune endocrine disease were identified. Patients 1 and 2 had classic stiff person syndrome and insidious-onset cerebellar ataxia, while Patient 3 had pure cerebellar ataxia with subacute onset. Patients received intravenous immunoglobulin therapy with no response in Patients 1 and 3 and partial recovery in Patient 2. Conclusion CA-GAD-ab is rare and its clinical presentation may hamper diagnosis. Clinicians should be able to recognize this potentially treatable autoimmune cerebellar ataxia.
RESUMO A enzima ácido glutâmico descarboxilase (GAD), presente nos neurônios GABAérgicos e células beta do pâncreas, catalisa a conversão do ácido gama-aminobutírico (GABA). O cerebelo é altamente susceptível a mecanismos imunomediados, sendo a ataxia cerebelar associada ao anticorpo anti-GAD (CA-GAD) uma doença potencialmente tratável. Embora rara, sua frequência é crescente, com poucos casos descritos. Métodos Estudo retrospectivo e descritivo avaliando características clínicas e desfechos da CA-GAD. Resultados Três pacientes com CA-GAD, altos títulos de anti-GAD e doença endócrina autoimune foram identificados. Os pacientes 1 e 2 tinham síndrome da pessoa rígida em forma clássica e apresentação insidiosa da ataxia cerebelar, enquanto o paciente 3 tinha ataxia cerebelar pura e apresentação subaguda. Os pacientes 1 e 3 não melhoraram com imunoglobulina intravenosa e o paciente 2 teve recuperação parcial. Conclusão A CA-GAD é rara e pode ter apresentação clínica desafiadora. Os médicos devem ser capazes de reconhecer essa forma potencialmente tratável de ataxia cerebelar autoimune.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Autoantibodies/blood , Cerebellar Ataxia/complications , Glutamate Decarboxylase/blood , Magnetic Resonance Imaging , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/immunology , Cerebellar Ataxia/drug therapy , Retrospective Studies , Treatment Outcome , Immunoglobulins, Intravenous/therapeutic use , Glutamate Decarboxylase/immunologySubject(s)
Antigens, Neoplasm/blood , Autoantibodies/blood , Cerebellar Ataxia/complications , Encephalitis/complications , Hashimoto Disease/complications , Hearing Loss/etiology , Nerve Tissue Proteins/blood , Adult , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/immunology , Encephalitis/diagnosis , Encephalitis/immunology , Hashimoto Disease/diagnosis , Hashimoto Disease/immunology , Humans , MaleSubject(s)
Autoantibodies/blood , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/immunology , Glutamate Decarboxylase/immunology , Seizures/immunology , Vitiligo/immunology , Cerebellar Ataxia/blood , Cerebellar Ataxia/complications , Diagnosis, Differential , Female , Humans , Thyroid Diseases/blood , Thyroid Diseases/diagnosis , Thyroid Diseases/immunology , Vitiligo/blood , Vitiligo/diagnosis , Young AdultABSTRACT
Neurological disorders associated with glutamic acid decarboxylase (GAD) antibodies are rare pleomorphic diseases of uncertain cause, of which stiff-person syndrome (SPS) is the best-known. Here, we described nine consecutive cases of neurological disorders associated with anti-GAD, including nine patients with SPS and three cases with cerebellar ataxia. Additionally, four had hypothyroidism, three epilepsy, two diabetes mellitus and two axial myoclonus.
Subject(s)
Antibodies/blood , Cerebellar Ataxia/immunology , Glutamate Decarboxylase/immunology , Stiff-Person Syndrome/immunology , Adolescent , Adult , Brazil , Cerebellar Ataxia/cerebrospinal fluid , Cerebellar Ataxia/diagnosis , Child , Electrodiagnosis/methods , Female , Humans , Male , Middle Aged , Parietal Cells, Gastric/immunology , Stiff-Person Syndrome/cerebrospinal fluid , Stiff-Person Syndrome/diagnosis , Young AdultABSTRACT
Neurological disorders associated with glutamic acid decarboxylase (GAD) antibodies are rare pleomorphic diseases of uncertain cause, of which stiff-person syndrome (SPS) is the best-known. Here, we described nine consecutive cases of neurological disorders associated with anti-GAD, including nine patients with SPS and three cases with cerebellar ataxia. Additionally, four had hypothyroidism, three epilepsy, two diabetes mellitus and two axial myoclonus.
Distúrbios neurológicos associados com anticorpos anti-GAD são doenças pleomórficas, raras, de causa incerta, das quais a rigidez muscular espasmódica (SPR) é a mais conhecida. Neste estudo, descrevemos nove casos consecutivos de distúrbios neurológicos associados com a presença de anticorpos anti-GAD, incluindo nove pacientes com SPR e três casos com ataxia cerebelar. Adicionalmente, foram encontrados quatro casos com hipotireoidismo, três com epilepsia, dois com diabetes mellitus e dois casos com mioclonia axial.
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Young Adult , Antibodies/blood , Cerebellar Ataxia/immunology , Glutamate Decarboxylase/immunology , Stiff-Person Syndrome/immunology , Brazil , Cerebellar Ataxia/cerebrospinal fluid , Cerebellar Ataxia/diagnosis , Electrodiagnosis/methods , Parietal Cells, Gastric/immunology , Stiff-Person Syndrome/cerebrospinal fluid , Stiff-Person Syndrome/diagnosisSubject(s)
Humans , Male , Middle Aged , Autoantibodies/blood , Autoimmune Diseases/immunology , Cerebellar Ataxia/immunology , Glutamate Decarboxylase/immunology , Immunoglobulins, Intravenous/therapeutic use , Autoimmune Diseases/therapy , Cerebellar Ataxia/therapy , Immunoglobulins, Intravenous/immunology , Severity of Illness Index , Treatment OutcomeSubject(s)
Autoantibodies/blood , Autoimmune Diseases/immunology , Cerebellar Ataxia/immunology , Glutamate Decarboxylase/immunology , Immunoglobulins, Intravenous/therapeutic use , Autoimmune Diseases/therapy , Cerebellar Ataxia/therapy , Humans , Immunoglobulins, Intravenous/immunology , Male , Middle Aged , Severity of Illness Index , Treatment OutcomeABSTRACT
A family suffering an autosomal dominant form of late onset hereditary cerebellar ataxia is described. Eight affected family members were personally studied, and data from another four were obtained through anamnesis. The mean age of onset was 37.1 +/- 5.4 years (27-47 years). The clinical picture consisted basically of a pure ataxic cerebellar syndrome. CT-scan disclosed diffuse cerebellar atrophy with relative sparing of the brainstem and no involvement of supratentorial structures. Neurophysiological studies (nerve conduction, VEP and BAEP) were normal. Twenty-six individuals were typed for HLA histocompatibility antigens. Lod scores were calculated with the computer program LINKMAP. Close linkage of the ataxia gene with the HLA system in this family could be excluded--0 = 0.02, z = (-2.17)--and the overall analysis of the lod scores suggest another chromosomal location than chromosome 6.
Subject(s)
Cerebellar Ataxia/genetics , Chromosome Aberrations/genetics , Chromosomes, Human, Pair 6 , Genetic Linkage/genetics , HLA Antigens/isolation & purification , Adult , Cerebellar Ataxia/immunology , Chromosome Disorders , Female , Humans , Male , Middle Aged , PedigreeABSTRACT
Descreve-se uma família afetada por forma autossômica dominante de ataxia cerebelar de início tardio (acima dos 20 anos). Oito membros da família säo estudados e dados de outros quatro afetados pela doença foram obtidos por anamnese. A média de idade de início da doença foi 37,1 ñ 5,4 anos (27-47 anos). O quadro clínico consistia basicamente de síndrome cerebelar de caráter lentamente progressivo, sem ocorrência concomitante de sinais ou sintomas decorrentes de envolvimento de outros sistemas. Estudo tomográfico computadorizado mostra atrofia cerebelar difusa com relativa preservaçäo do tronco cerebral e das estruturas supratentoriais. Estudos neurofisiológicos (neuroconduçäo motora/sensitiva, potenciais evocados visuais e auditivos) foram normais. Vinte e seis pessoas da família foram tipados para antígenos de histocompatibilidade HLA. Escores lod foram calculados utilizando programa de computador denominado LINKMAP. Ligaçäo estreita com o sistema HLA nesta família foi excluida - 0=0,02, z=(-2,17) - e a análise global dos escores lod sugerem que o gene mutante nesta família näo se localiza no cromossomo 6