Annals of Movement Disorders

: 2023  |  Volume : 6  |  Issue : 1  |  Page : 33--35

Paraneoplastic cerebellar degeneration heralding recurrent metastatic carcinoma breast

Ram Bhupal Reddy Nagireddy, Anand Kumar, Deepika Joshi 
 Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Correspondence Address:
Deepika Joshi
Department of Neurology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh – 221005

How to cite this article:
Nagireddy RB, Kumar A, Joshi D. Paraneoplastic cerebellar degeneration heralding recurrent metastatic carcinoma breast.Ann Mov Disord 2023;6:33-35

How to cite this URL:
Nagireddy RB, Kumar A, Joshi D. Paraneoplastic cerebellar degeneration heralding recurrent metastatic carcinoma breast. Ann Mov Disord [serial online] 2023 [cited 2023 May 28 ];6:33-35
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Paraneoplastic cerebellar degeneration (PCD) is a rare condition, commonly associated with breast, gynecological, and lung cancer and lymphomas.[1] PCD may rarely present several years after treatment of primary breast malignancy, revealing metastatic disease [2].

A 47-year-old woman presented with progressive unsteadiness while walking with worsening truncal instability],[ slurring of speech],[ and increasing difficulty with fine motor tasks due to incoordination for 6 months. At the time of admission],[ she needed the support of one person to walk. There were no constitutional symptoms],[ headaches],[ seizures],[ and hearing or visual disturbances. Her past history revealed that she had a stage-T4BN1M0 infiltrative ductal malignancy in the right breast. Her hormone receptors (estrogen receptor/progesterone receptor) were negative. In addition],[ she was Her2Neu 3+],[ for which she was treated with neoadjuvant chemotherapy and modified radical mastectomy 4 years ago. Histopathological examination showed grade-2 ductal carcinoma with all margins free from the tumor. There was no known family history of malignancy. Her vitals and general physical examination (including breast) were normal. There was no lymphadenopathy. Neurological assessment revealed prominent cerebellar signs],[ including bilateral upper limb dysmetria],[ intention tremor],[ scanning speech],[ and gait and truncal ataxia [Videos 1 and 2] [SUPPORTING:1] [SUPPORTING:2]. The Scale for the Assessment and Rating of Ataxia (SARA scale)[3] revealed a score of 29/40. She had normal muscle tone, power, sensation, and symmetrical reflexes throughout her upper and lower limbs. Examination of the cranial nerves did not reveal any abnormalities. Gaze-evoked nystagmus was observed. Her routine laboratory tests were unremarkable, and the serum tumor markers were within the normal range. Chest X-ray and ultrasound of the abdomen and pelvis revealed no abnormality. Brain and spine magnetic resonance imaging were normal. Cerebrospinal fluid analysis revealed no cells, normal sugar levels, slightly increased protein level (70 mg/dl) with no oligoclonal bands, and it was negative for malignant cells. Serum was tested for onconeural antibodies, including anti-Yo, anti-Hu, anti-Ri, anti-CV2, anti-Ma2, and anti-amphiphysin. A high titer of anti-Yo antibodies (1:1,000) was detected in the serum sample using immunoblot assay with the dilution of 1:101. Therefore, the possibility of recurrence of breast cancer was considered and whole-body positron emission tomography–computed tomography was performed, which showed hypermetabolic right infraclavicular retro pectoral node with no evidence of active disease elsewhere. Ultrasound-guided fine-needle aspiration cytology of the lymph node was positive for metastatic cells. Following the oncology consultation, the patient was started on chemotherapy and surgery was planned (excision of the lymph node); however, patient did not provide consent for surgery. A pulse dose of 1 g of methylprednisolone for 5 days was given with a repeating pulse after 1 month. During the 3-month follow-up, she demonstrated symptomatic improvement with a SARA score of 22/40.

PCD is one of the common subtypes of paraneoplastic neurological syndromes. It is characterized by subacute onset of gait instability that progresses to a pancerebellar syndrome with vertigo, diplopia, dysarthria, and truncal and appendicular ataxia, which eventually stabilizes but leaves the patient incapacitated. PCD occurs as a consequence of autoimmune-mediated destruction of the cerebellar Purkinje cells,[4] because of cross-reactivity between onconeural antigens (anti-Yo) and dendritic Purkinje cells. Anti-Yo antibodies specifically target the cerebellar Purkinje cells, resulting in extensive Purkinje cell death. The underlying mechanism is generally considered to be an immunological response to cerebellar degeneration-related protein 2, which is ectopically expressed by tumor cells.[4] Studies have suggested that HER2-positive breast cancers are prone to early regional lymph node invasion, favoring the development of anti-Yo antibodies in the cerebellar degeneration-related protein 2-positive cancer cells, which are restricted to HER2-positive breast tumors.[5] The tumors most frequently associated with PCD are small-cell lung carcinoma, ovarian and breast cancers, and Hodgkin’s lymphoma, with anti-Yo (Purkinje cell cytoplasmic autoantibody type 1) being the most frequent (70%) antibody associated with breast and gynecological malignancies.[4] The other main autoantibodies associated with PCD are listed in [Table 1]. In approximately 60% of the cases, the patients present with PCD months or years before underlying malignancy is diagnosed. Approximately 30% of the patients with presumed paraneoplastic syndromes do not have detectable antibodies. Our patient had been treated for an infiltrative ductal malignancy approximately 4 years ago and was in complete remission for the next 3.5 years when she developed a cerebellar syndrome with anti-Yo antibodies positivity. A metastatic right infraclavicular retro pectoral node was detected on positron emission tomography–computed tomography. Therefore, the occurrence of PCD revealed an occult metastatic lymph node in our patient, which is extremely rare and has been previously described in only two case reports.[2],[6] The patient had symptomatic improvement in her disabling ataxia, and chemotherapy and surgery were considered for the tumor.{Table 1}

The presence of characteristic anti-onconeural antibodies can guide the search for an underlying tumor. Early detection helped us reinstitute symptomatic treatment (for ataxia) as well as specific treatment (for malignancy), which improved the patient’s quality of life.

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