Abstract
<strong>Background:</strong> Antibodies against glutamic acid decarboxylase (GAD) are associated with Stiff Person Syndrome (SPS). <strong>Case report:</strong> A 50-year-old woman presented with symptoms progressed over 9 years, resulting in a cerebellar ataxia and right upper limb tremor. Investigations revealed elevated serum and CSF anti-GAD antibody titres (98.6 and 53.4 μ/ml, respectively). Treatment included intravenous immunoglobulin and immunomodulation (infliximab and rituximab), improving her stiffness, but with no impact on the ataxia-related symptoms. Subsequent high-dose steroids led to diabetic ketoacidosis and unmasking of an insulin-dependent diabetes mellitus. <strong>Discussion:</strong> This case illustrates several key features: (1) the combined clinical picture of SPS and cerebellar ataxia is a rare phenotype associated with anti-GAD antibodies; (2) the cerebellar ataxia described was progressive and poorly responsive to immunomodulatory therapy; and (3) the potential for development of further autoimmune sequelae in response to immunosuppression, namely, the development of insulin-dependent diabetes in response to treatment with high-dose oral steroids.
Highlights
Antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme involved in γ-aminobutyric acid (GABA) synthesis, are associated with several neurological disorders, including Stiff Person Syndrome (SPS), epilepsy, myasthenia gravis, limbic encephalitis and cerebellar ataxia.[1,2]
This case illustrates some of the systemic features of disease associated with GAD auto-antibodies, which are more typically associated with the destruction of pancreatic islet beta cells in autoimmune type 1 diabetes.[6]
In spite of >45 case reports and case series describing cohorts of individuals with features of SPS and raised anti-GAD titres,[7] the constellation of symptoms described in this case, namely, the combination of SPS and insidious-onset but progressive cerebellar ataxia, remains rarely reported
Summary
Antibodies against glutamic acid decarboxylase (GAD), the rate-limiting enzyme involved in γ-aminobutyric acid (GABA) synthesis, are associated with several neurological disorders, including Stiff Person Syndrome (SPS), epilepsy, myasthenia gravis, limbic encephalitis and cerebellar ataxia.[1,2] concurrent presentation of SPS, cerebellar ataxia and positive anti-GAD antibodies has only been reported in a limited number of cases previously.[3,4,5] Here, we describe such a case which demonstrates (1) this rare combination of clinical features, including SPS and cerebellar ataxia, with limb and bulbar features; (2) symptom resistance, most notably the cerebellar ataxia, to multiple immunomodulatory therapies; and (3) development of further autoimmune sequelae, namely, insulin- dependent diabetes, following treatment with high-dose steroids. Clinical examination at this time demonstrated ongoing involuntary stiffness of the right side, but no overt clinical signs of ataxia.
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