Long-term efficiency of intravenously administered immunoglobulin in anti-Yo syndrome with paraneoplastic cerebellar degeneration

Paraneoplastic cerebellar degeneration (PCD) is a rare heterogeneous group of disorders associated with cancer and anti-neuronal antibodies. Patients display symptoms reflecting cerebellar dysfunction including dysarthria, severe ataxia and abnormal oculomotor functions. Anti-Yo antibodies, also often called Purkinje cell antibodies type 1 (PCA-1), occur in patients with PCD having a history of tumors of the ovary, endometrium, fallopian tube or breast cancer [6, 11]. The treatment of PCD associated with antiYo antibodies is very limited and does usually not respond to immunosuppressive or tumor therapy. We report improvement and stabilization in a patient with an anti-Yo syndrome with PCD secondary to ovarian carcinoma through 10 years of treatment with intravenous immunoglobuline (IVIG). A 72-year-old female patient was diagnosed with an ovarian carcinoma with TNM-classification pT3, pN1, G3 at the age of 61 years. The patient subsequently underwent surgery followed by chemotherapy with Taxol 175 mg/m and carboplatin (according AUC 6) under hyperthermic conditions. The therapy was well tolerated without serious side effects. However, treatment resulted in a mild axonal motor and accentuated sensory polyneuropathy. At age 62 years, she presented with a progressive cerebellar syndrome with low saccadic eye movement and saccadic dysmetria, diplopia and horizontal spontaneous nystagmus as well as persistent ptosis bilaterally. She displayed marked limb and cerebellar ataxia with inability to walk unaided, an increased tendency to fall, and severe limb pain. Deep tendon reflexes were decreased in lower extremities; no pathological reflexes were seen. Additionally distal symmetric sensible polyneuropathy with hypaesthesia was present. Analysis of blood and cerebrospinal fluid (CSF) showed an elevated titer for Yo antibodies (serum 1:7,680, CSF 1:240) and a slight pleocytosis. MRI of the brain was normal. Under the diagnosis of anti-Yo syndrome with PCD, this patient was treated with IVIG initiated at age 62 years. Initially a total of 150 g of IVIG was applied every 3 weeks. The response was prompt with improvement of gait ataxia and pain. Walking was much easier and no further falls were reported. During IVIG therapy the antibody titers decreased to levels of about 1:480. Follow-up MRIs of the brain displayed normal findings. Treatment intervals could be prolonged and she received a total of 40 dosages of an average of 145 g of IVIG (90–200 g of IVIG) within the last 10 years with an average interval of 3 months (Fig. 1). Worsening of ataxia re-occurred after about 2 months after the last IVIG treatment. The IVIG product had to be changed three times after showing mild side effects such as fever and headache, which was also the reason for the dosage variation. IVIG is given with the comedication of i.v. prednisolone and i.v. dimetindenmaleat, an antihistamine. At the age of 68 years, a treatment escalation with rituximab (four times 375 mg/m body surface area) showed no further clinical benefits. During treatment with the co-medication 3,4-diaminopyridine, oculomotor dysfunctions like diplopia and nystagmus disappeared. Until today all cancer follow up examinations revealed no evidence of any new tumor or metastasis. Anti-Yo antibodies are, with a few exceptions, detected in patients with PCD secondary to breast, ovary and female genital tract carcinomas. Immunosuppressive or immunomodulatory therapies were considered due to the J. Schessl (&) M. Schuberth P. Reilich P. Schneiderat N. Strigl-Pill M. C. Walter B. Schlotter-Weigel B. Schoser Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians University of Munich, Ziemssenstr. 1 A, 80336 Munchen, Germany e-mail: joachim.schessl@med.uni-muenchen.de