GAD-ab-associated movement disorder in a male patient with breast cancer

Abstract

GAD-ab-associated paraneoplastic syndromes are a rare condition, especially in male patients. We describe the unusual case of a man with a combined movement disorder and ataxia due to breast cancer. This 52-year-old man from Russia presented with a progressive dysarthrophonia and a complex movement disorder. Initial symptoms started 9 months previously with exhaustion, fatigue, and a muscular weakness. The symptoms were classified as endogenous depression and treatment was started with sertraline (for 4 weeks) and olanzapine (for 2 weeks). In spite of this, the symptoms worsened and the medication was stopped. Two months later, slurred speech and spontaneous movements of the oromandibular and brachial muscles occurred. Especially the impaired phonation was very disabling for the patient because of his profession as an opera singer. His past medical history was significant for a breast carcinoma 10 years earlier. He had been treated with radical mastectomy, but no chemotherapy or radiation treatment. The patient presented in our hospital in May 2010 with a severe dysarthrophonia and dysphagia. He showed permanent dystonic movements of the platysma and the submandibular muscles, athetotic movements of the upper and lower extremities, and a body swaying. While some hyperkinetic movements seemed to be rhythmic, he also presented asymmetric myoclonic jerks and an ataxia of the trunk and extremities. A chest CT was performed (Fig. 1) and multiple focal lesions in the lung led to a CT-controlled puncture. Biopsy proved metastases of the mamma carcinoma. Because of the high probability of a paraneoplastic syndrome, a laboratory testing for paraneoplastic antibodies in serum and CSF was performed. Glutamate decarboxylase antibodies (GAD) were elevated (serum 1,600 U/ml, liquor 2,200 U/ ml). Two leukocytes were detected in the CSF and the protein was slightly elevated (53 mg/dl), and oligoclonal bands and other antibodies were negative (Anti-Yo, -Hu, Ri, -2CV). Brain MRI with multiple sequences including Gd contrast was normal. Electromyographic findings were consistent with a cerebellar tremor. With the diagnosis of a GAD-Ab-associated paraneoplastic syndrome, we started four cycles of immunoabsorption therapy [1]. Within 1.5 weeks, the patient’s neurological symptoms nearly completely disappeared. GAD-Ab were no longer detectable in a control 10 days after the last immunoadsorption. Subsequently, chemotherapy with cisplatin and gemcitabine was started [2] and the patient was relocated to his home country. The rapid response to immunoadsorption suggests the elimination of pathogenic antibodies in the serum. Whether the GAD-antibodies that were detectable before but not after the therapy are just a marker of the paraneoplastic disease or really play a role in the pathogenesis of the movement disorder remains elusive. Glutamate decarboxylase is the rate-limiting enzyme for GABA synthesis. It is well known as a major autoantigen in type 1 diabetes mellitus [3]. It is also well known to be positive in patients with stiff-person syndrome [4]. Over the years, a variety of other neurological syndromes have been described in connection with GAD positivity, for example cerebellar ataxia, epilepsy, myasthenia gravis, and limbic encephalitis [5]. The majority of patients are female C. Venker (&) M. Kramer P. Berlit Department of Neurology, Alfried Krupp-Hospital Essen, Essen, Germany e-mail: conrad.venker@gmx.de