anti-Yo Paraneoplastic Cerebellar Degeneration Research Articles

Anti-Yo Paraneoplastic Cerebellar Degeneration and Breast Cancer: A Long Survival of Persistent Cerebellar Syndrome

Paraneoplastic neurological syndromes (PNS) occur in 1–3% of all cancer patients with several cancer-related neurologic diseases involving any part of the nervous system. Paraneoplastic cerebellar degeneration (PCD) is a specific type of PNS characterized by sub-acute cerebellar syndrome with trunk and limb ataxia, dysarthria, diplopia, and vertigo. We report herein the case of a 70-year-old female patient with cerebellar symptoms and transient anti-Yo antibody PCD positivity manifested three years after a breast cancer diagnosis who is currently neurologically stable after an extended follow-up.

Combined Cerebellar and Spinal Cord Deficits Caused by an Underlying Gynecologic Malignancy

Paraneoplastic cerebellar degeneration (PCD) is an uncommon autoimmune disorder targeting antigens within the nervous system and is usually associated with an underlying malignancy. Neurologic symptoms frequently precede the cancer diagnosis, which is most often seen in women with breast or gynecologic tumors. Anti-Yo-related PCD is the most common PCD syndrome, and one of the best understood. Although cerebellar signs are characteristic of anti-Yo PCD, myelopathy is an unusual presentation of anti-Yo PCD based on published case series and reports. Unfortunately, the prognosis for anti-Yo PCD is often poor, and most patients become bedridden. We report a case highlighting a severe presentation of cerebellar degeneration along with an unusual finding of myelopathy in a patient with a newly diagnosed gynecologic cancer.

P14.102 Cerebellar atrophy patterns in paraneoplastic cerebellar degeneraiton and spinocerebellar ataxia 1 (SCA1)

Abstract BACKGROUND Brain and more specifically cerebellar atrophy is a major radiological finding in both Paraneoplastic Cerebellar Degeneration (PCD) with anti-Yo antibodies and Spinocerebellar Ataxia type 1 (SCA1).We sought to analyze the different brain volumetric patterns of cerebellar atrophy in these diseases. MATERIAL AND METHODS We performed a retrospective multicentric study (Paris, Lyon, Barcelona reference centres) with either anti-Yo PCD (n=16) or SCA1 (n=17) and 30 healthy subjects paired by age. We used VolBrain and CERES algorithms to obtain the brain and cerebellum segmentation, respectively as well as the cortical thickness. We used a Sparse Canonical Correlation Analysis (SCCAN) and Voxel Brain Morphometry (VBM) with family wise error correction to analyze volumetric differences between the different conditions. RESULTS SCA patients were younger than PCD patients (p<0.05, ANOVA). In univariate analysis, most of the atrophic regions (p<0.05) were common between PCD and SCA1 compared to controls. Isolated cortical thickness and grey matter analysis showed predominant atrophy in PCD patients. Multivariate analysis using SCCAN and VBM confirmed these results. We identified a particular atrophy pattern in PCD patients involving lobules III to VII. We observed a more diffuse atrophy distribution in SCA1 patients and a lower cortical atrophy in PCD patients. CONCLUSION We described the specific pattern of topographic cerebellar atrophy in PCD and SCA1 patients. The cerebellar atrophy in PCD is mainly localized in the neocerebellum.

Transcriptomic immune profiling of ovarian cancers in paraneoplastic cerebellar degeneration associated with anti-Yo antibodies

BackgroundParaneoplastic neurological syndromes are rare conditions where an autoimmune reaction against the nervous system appears in patients suffering from a tumour, but not linked to the spreading of the tumour. A break in the immune tolerance is thought to be the trigger.MethodsThe transcriptomic profile of 12 ovarian tumours (OT) from patients suffering from paraneoplastic cerebellar degeneration (PCD) linked to anti-Yo antibodies (anti-Yo PCD OT) was compared with 733 ovarian tumours (OT control) from different public databases using linear model analysis.ResultsA prominent significant transcriptomic over-representation of CD8+ and Treg cells was found in anti-Yo PCD OT, as compared to the OT control. However, the overall degree of immune cell infiltration was similar, according to the ESTIMATE immune score. We also found an under-representation of M2 macrophages in anti-Yo PCD OT. Furthermore, the differentially expressed genes were enriched for AIRE-related genes, a well-known transcription factor associated with a broad range of autoimmune diseases. Finally, we found that the differentially expressed genes were correlated to the transcriptomic profiling of the cerebellar structures.ConclusionsOur data pinpointed the enrichment of acquired immune response, particularly high density of CD8+ lymphocytes, and high-level expression of CDR-related antigens in anti-Yo PCD OT.

Complex HLA association in paraneoplastic cerebellar ataxia with anti-Yo antibodies

Anti-Yo paraneoplastic cerebellar degeneration (PCD) is a devastating autoimmune complication of gynecological cancers. We hypothesized that as for other autoimmune diseases, specific HLA haplotypes are associated. We conducted high resolution HLA typing of Class I/Class II in 40 cases versus ethnically matched controls. Three cases with anti-Yo antibodies and peripheral neuropathy were also included. We detected protective effects of DPA1*01:03~DPB1*04:01 (OR=0, p=0.0008), DRB1*04:01~DQA1*03:03(OR=0, p=0.0016) and DPA1*01:03~DPB1*04:01 (OR=0.35, p=0.0047) overall. Increased DRB1*13:01~DQA1*01:03~DQB1*06:03 was also found in PCD ovarian cases (OR=5.4, p=0.0016). These results suggest differential genetic susceptibility to anti-Yo per cancer and with a primary HLA Class II involvement.

P10.02 * UTERINE CARCINOSARCOMA WITH PARANEOPLASTIC CEREBELLAR DEGENERATION: CASE ANALYSIS WITH LITERATURE REVIEW

INTRODUCTION: Paraneoplastic neurologic syndromes (PNS), a heterogeneous group of oncologic immune-mediated neurologic disorders, often antedate cancer diagnosis. PNS recognition results in early cancer screening/treatment. Paraneoplastic cerebellar degeneration (PCD) is an aggressive/debilitating/fatal PNS characterized by pancerebellar symptoms – progressive ataxia/dysarthria/nystagmus/vertigo. PCD is predominantly associated with breast/gynecologic cancers. Though 12 onconeural antibodies are implicated in PCD, anti-Yo antibody is the most common/specific antibody seen in PCD. We present the first case of anti-Yo PCD associated with uterine carcinosarcoma. METHOD: Case analysis. CASE: 78yo female presented with month-long history of ataxia/gait instability/falls and abrupt onset diplopia/nausea/vomiting without fever/syncope/headache /dysarthria. Past medical history was significant for right breast T1 N0 invasive ductal carcinoma s/p partial mastectomy and adjuvant whole breast radiation that occurred 1 year prior to presentation. Neurologic exam revealed intact language/comprehension, left sixth cranial nerve palsy, truncal/limb ataxia, bilateral horizontal nystagmus, and symmetric 3+ deep tendon reflexes without focal deficits or dystonia noted. Routine blood work was unremarkable. Brain MRI with/without contrast noted no evidence of metastatic disease/demyelinating process/hemorrhage/infarction. She declined CSF studies. Within two months, she developed dysarthria/dysphagia and was unable to stand without assistance due to progressive ataxia. PNS laboratory evaluation yielded high titer of anti-Yo antibody (1/245,760) with positive Western blot assay as the only onconeural antibody. Chest/abdomen/pelvis CT scan demonstrated multiple soft tissue lesions in the omentum with bilateral sub-centimeter pulmonary nodules. Tumor marker analysis noted elevated CA-125/CA-27.29/CA-15.3. CT guided biopsy of omental lesions revealed poorly differentiated carcinosarcoma. Immunohistochemistry confirmed malignant stage IV uterine carcinosarcoma. Chemotherapy with IVIG was initiated. Though tumor burden size decreased, PCD progressed (bedbound, increased anti-Yo antibody titers). Rapid neurologic decline required hospice 8 months after PCD diagnosis associated with uterine carcinosarcoma. She died 1 month later. CONCLUSIONS: This case confirms anti-Yo PCD association with uterine carcinosarcoma. PCD requires early cancer screening/treatment and aggressive multi-modal immunotherapy interventions. Clinicians should have a low threshold for PCD. Double primary cancers must be considered. Prospective trials addressing anti-Yo PCD therapeutic interventions, illness progression, associated cancer, double primary, and survival are indicated. Clinicians require further education regarding PCD and other PNS.

Anti‐Yo mediated paraneoplastic cerebellar degeneration in the context of breast cancer: a case report and literature review

Paraneoplastic syndromes are of interest to psycho-oncologists because they may be misdiagnosed initially as primary psychiatric disorders and can have profound neuropsychiatric and psychosocial sequelae. Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic syndrome which destroys Purkinje cells of the cerebellum and causes trunk and limb ataxia, dysarthria, diplopia, and vertigo, which often precede the diagnosis of cancer. Anti-Yo PCD is a devastating syndrome that significantly worsens prognosis in terms of functional ability and survival. We present the case of a woman with progressive cerebellar deficits, which were misdiagnosed for several months before breast cancer and anti-Yo antibodies were discovered. PCD may be misdiagnosed as a primary psychiatric disorder. Results of neuropsychological assessment in this case found subtle attentional dysfunction but relatively preserved cognitive functioning in other domains. The literature relating to PCD and psychiatric manifestations of cerebellar disease are reviewed. The limitations of our current understanding of non-motor cerebellar function are highlighted, asserting the need for further study in this area.

Anti-Yo Associated Paraneoplastic Cerebellar Degeneration in a Man with Large Cell Cancer of the Lung

Purkinje cell cytoplasmic antibody type 1 (PCA-1), or anti-Yo, is the most frequently detected autoantibody in paraneoplastic cerebellar degeneration (PCD). The vast majority of cases of anti-Yo PCD, however, occur in females over 60 years old and are associated with gynecologic tumors. Only 10 cases have been reported in males, and only 2 were associated with cancer of the lung. Here we describe the youngest known case of PCA-1 positive PCD in a male, whose lung tumor was undetectable even on FDG-PET.

Pathogenesis of anti-Yo positive paraneoplastic cerebellar degeneration

Paraneoplastic cerebellar degeneration (PCD) is a neurological disorder affecting the cerebellum and is believed to be immune-mediated. Anti-Yo PCD is associated with gynaecological and breast cancer tumours and the presence of these tumours is believed to invoke an immune response. The immune response includes both anti-Yo antibodies and cytotoxic T-lymphocytes that are specific for the Cdr2 antigen expressed in Purkinje cells of the cerebellum. Although both have been implicated in the pathogenic manifestation of PCD neither have been shown to be directly involved. The detection of the anti-Yo antibody greatly aids in the diagnosis of PCD and helps in uncovering the underlying neoplasm before it becomes symptomatic. Treatment of PCD has been targeted at suppressing the immune response but has been unsuccessful so far. The lack of a suitable animal model makes it difficult to study the pathogenic process directly leaving many questions unanswered about PCD pathogenesis.