Brainstem and spinal cord involvement in a paraneoplastic syndrome associated with anti-Yo antibody and breast cancer

Abstract

Paraneoplastic neurological syndromes (PNS) are associated with breast cancer in\1% of cases [1]. Anti-Yo/PCA-1 antibody is usually detected in female patients with breast or gynaecologic cancer and is most commonly associated with progressive cerebellar degeneration (PCD) [2][3][4][5].Here we describe a case of a 60-year-old woman who, in May 2008, complained of progressive weakness of lower limbs followed, after 2 months, by dysesthesias in the four limbs, dysphagia, diplopia and sensory ataxia. Total body computed tomography (CT) scan, brain and spinal cord magnetic resonance imaging (MRI) were normal, electromyography (EMG) showed evidence of acute and chronic denervation in the four limb muscles, oligoclonal bands were present in the cerebrospinal fluid and serum anti-onconeural antibodies were negative. She was treated with steroids for several months with partial benefit but soon after drug discontinuation her symptoms worsened. At our first neurological examination in January 2010, the patient was unable to walk for severe sensory ataxia and showed lower limb weakness and spasticity, mild dysarthria, dysphagia, diplopia and dysesthesias in the four limbs. Sensory and motor evoked potentials were altered both at upper and lower limbs and EMG showed evidence of acute and chronic denervation in the muscles of upper and lower extremities. At that time, serum anti-Yo/PCA-1 antibody was positive. Total body CT scan and mammography showed evidence of a nodular opacity associated with two clusters of retroareolar microcalcifications in the left breast. A total body 2-deoxy-2-18 F-fluoro-D-glucose positron emission tomography ( 18 FDG PET)/CT imaging showed high metabolic activity in the right axillary lymph nodes but ultrasound scan (US) and MRI confirmed the left breast calcifications with no evidence of axillary lymph node pathological alterations bilaterally. The left mammary lesion was surgically removed in March 2010. Histopathological examination revealed the presence of foci of ductal carcinoma in situ of G2 grade. Radiotherapy and hormonal therapy were started in April 2010. Soon after the surgery, the neurological symptoms progressively improved. At the last neurological examination in July 2010, the ataxia was reduced and the patient was ambulatory without aid or rest for about 10 m, with only a mild proximal weakness of the legs and diplopia persisting. The EMG evaluation showed improvement mainly at the lower limbs with reduction of acute denervation signs.Despite the fact that, in our patient, the clinical picture was not evocative of a classical PNS, we suspected a paraneoplastic encephalomyelitis; we repeated tests for anti-onconeural antibodies and diagnostic investigations for cancer, and we found serum positivity for anti-Yo/ PCA-1 antibody associated with a ductal breast carcinoma in situ.Very few cases of anti-Yo/PCA-1 antibody associated PNS, different from PCD, have already been described including several cases of peripheral neuropathy [6, 7] and a case of motor neuron disease involving bot...

Neural antigen‐specific autoimmune disorders

“…The most profound and frequent but not exclusive neurological manifestation is subacute cerebellar ataxia. Cerebrocortical, brainstem, spinal cord, and peripheral/autonomic manifestations are also encountered and sometimes are the initial, predominant, or exclusive finding(s) . These diverse neurological manifestations are consistent with the distribution of the PCA‐1 antigen which is not confined to the cerebellum and is expressed in spinal motor neurons and Schwann cells of peripheral nerve .…”

Case Report: A False Negative Case of Anti-Yo Paraneoplastic Myelopathy

“…Most cases of PNM are associated with antibodies against amphiphysin, Hu, or CV2/CRMP5, while anti-Yo antibodies are typically associated with PCD (19). Anti-Yo PCD with superimposed myelopathy is uncommon (24,(26)(27)(28) and isolated anti-Yo myelopathy [(24), case 7] or myeloneuropathy rarer still (10). It is unknown why some anti-Yo patients lack obvious cerebellar findings on exam though this does not preclude subclinical cerebellar dysfunction.…”