anti-Yo Positive Paraneoplastic Cerebellar Degeneration Research Articles

Anti-Yo Positive Paraneoplastic Cerebellar Degeneration Associated with Ovarian Cancer: A Case Report and a Review of the Literature

Paraneoplastic cerebellar degeneration (PCD) is a rare n eurological disorder in cancer patients, characterized by a widespread loss of Purkinje cells associated with a progressive pancerebellar dysfunction. Furthermore, PCD is characterized by acute or subacute onset of neurological symptoms such as cerebellar ataxia, dysarthria and nystagmus due to tumor-induced autoimmunity against cerebellar antigens. It is believed that anti-Yo occurs usually in women and is most likely associated with gynecologic or breast cancers. PCD often precedes the cancer diagnosis by months to years. Here, we present a case involving a 52-year-old woman who developed PCD symptoms two months before the diagnosis of ovarian cancer, which was associated with high levels of anti-Yo antibodies

Acute Onset, Rapidly Progressive Anti-Yo Positive Paraneoplastic Cerebellar Degeneration, Associated with Ovarian Cancer, in the Setting of Immune Checkpoint Inhibitor Pembrolizumab Use: a Case Report (P8-1.004)

Acute Onset, Rapidly Progressive Anti-Yo Positive Paraneoplastic Cerebellar Degeneration, Associated with Ovarian Cancer, in the Setting of Immune Checkpoint Inhibitor Pembrolizumab Use: a Case Report (P8-1.004)

Anti-Yo positive paraneoplastic cerebellar degeneration associated with ovarian cancer: a rare case report

Anti-Yo positive paraneoplastic cerebellar degeneration associated with ovarian cancer: a rare case report

A case of anti-Yo positive paraneoplastic cerebellar degeneration masquerading as post-infectious cerebellitis

A case of anti-Yo positive paraneoplastic cerebellar degeneration masquerading as post-infectious cerebellitis

Anti-Yo positive paraneoplastic cerebellar degeneration in the setting of cholangiocarcinoma

Paraneoplastic neurological syndromes are a rare complication of malignancy. Subacute cerebellar ataxia, or paraneoplastic cerebellar degeneration, usually presents in women with a subcate onset of gait instability, followed by progressive limb and trunk ataxia, dysarthria, diplopia, and dysphagia that occurs in the setting of, or precedes the diagnosis of, a gynecologic or breast malignancy and clinically stabilizes within six months. The most common autoantibody associated with PCD is purkinje cell cytoplasmic antibody type 1, also known as anti-Yo. Here we describe the first reported case of a man with anti-Yo positive paraneoplastic cerebellar degeneration in the setting of occult cholangiocarcinoma.

Paraneoplastic cerebellar degeneration with anti-Yo antibodies associated with metastatic uveal melanoma

Paraneoplastic cerebellar degeneration (PCD) is characterized by subacute development of pancerebellar dysfunction as a remote effect of a systemic cancer and usually develops in patients affected by gynecological tumors. Uveal melanoma is a very rare disease with a severe prognosis.A 58-year-old man affected by uveal melanoma developed anti-Yo positive paraneoplastic cerebellar degeneration (PCD) 42months after the initial diagnosis. The onset and worsening of the neurological symptoms were parallel to the course of liver metastasis.To our knowledge this is the first case of PCD in a patient with uveal melanoma. We speculate that the cerebellar degeneration-related protein 2 (CDR2), to which the anti-Yo antibodies are directed, may have been expressed in melanoma cells and conferred proliferative advantage to the disease.

Diffuse cerebellar MR imaging changes in anti-Yo positive paraneoplastic cerebellar degeneration

A 48 year old lady presented with a month’s history of vertigo, nausea, and vomiting. Examination revealed nystagmus, mild limb-clumsiness (predominantly left sided) and mild gait ataxia. MR imaging demonstrated diffuse signal change within the cerebellar hemispheres (most prominent on the left), predominantly affecting the white matter but also the cerebellar cortex (Fig. 1). CSF examination revealed 52 lymphocytes (‘‘bland’’ on cytology), oligoclonal bands were not detected. The cerebellar findings progressed rapidly and she developed dysarthric speech and marked limb/truncal ataxia. Her symptoms plateaued within 3 months, by which time she was bedbound. An Anti-Yo antibody was detected in the serum. CT imaging demonstrated an area of abnormal tissue in the left breast; biopsy confirmed breast adenocarcinoma with axillary lymph node spread. She declined repeat cerebral imaging. While our patient’s clinical course is typical for an anti-Yo positive paraneoplastic cerebellar degeneration (PCD), the imaging findings are most unusual. Despite profound ataxia, brain imaging in PCD is usually ‘‘remarkably unremarkable’’, although cerebellar atrophy may be observed eventually [5, 6]. Very rarely PCD has been reported with imaging abnormalities, early in the course of the disease, in the context of anti-Tr [1] and anti-CRMP5 (anti-CV2) antibodies [2]. McHugh et al. [4] reported a case of anti-Yo positive PCD (secondary to ovarian adenocarcinoma) associated with signal abnormality in the right mesial temporal lobe on MRI. Interval imaging, following tumour resection, showed resolution of the temporal abnormality but a new focal cerebellar hyperintensity. To our knowledge, our case is the first to demonstrate diffuse cerebellar signal change on MRI in the context of anti-Yo positive PCD, expanding the radiological features recognised in this condition. The sensitivity of MRI for detecting such changes may be increased by imaging at high field strengths, as in this case (3.0 Telsa Philips Achieva; Best, The Netherlands). The pathological substrate of these imaging changes is unclear. Peterson et al. [5] examined three cases of anti-Yo positive PCD at postmortem, observing a diffuse loss of Purkinje cells but a notable absence of inflammatory infiltrates in the cerebellar cortex. However, inflammatory changes may be seen much earlier in the disease course. Giometto et al. [3] reported the post-mortem findings in a patient who died of a myocardial infarct 4 months after developing an anti-Yo positive PCD, observing CD8? lymphocyte infiltration in the cerebellum and cerebral cortex, and diffuse microglial upregulation of MHC-II throughout the brain. In conclusion, we describe a case of PCD with very unusual imaging features, characterised by diffuse signal abnormality within the cerebellar hemispheres. In order to C. P. Gilmore (&) P. Maddison Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, UK e-mail: chris.gilmore@nottingham.ac.uk

Paraneoplastic Cerebellar Degeneration with Anti-Yo Antibody in a Patient with HER2neu Overexpressing Breast Cancer: A Case Report with a Current Literature Review

Paraneoplastic cerebellar degeneration (PCD) is a rare paraneoplastic syndrome, occurring in <1% of breast cancers. We describe a 32-year-old female presenting with ataxia subsequently diagnosed with poorly differentiated breast cancer. She was serum anti-Yo antibody positive, with estrogen/progesterone receptor negative and HER2/neu receptor positive breast cancer. Neurological symptoms progressed despite modified radical mastectomy, supraclavicular lymphadenectomy, intravenous immunoglobulin, corticosteroids, transtuzumab, and combination chemotherapy. We performed a literature search, which found a possible association between anti-Yo positive PCD and HER2/neu-expressing breast cancer.

Unusual MRI abnormalities in anti-Yo positive "pure" paraneoplastic cerebellar degeneration

Sirs: anti-Yo or anti-Purkinje Cell Antibody (PCA) is one of the commonest onco-neural antibodies recognized within the CNS. The associated paraneoplastic cerebellar degeneration (PCD) is a clearly defined syndrome with over 200 reported cases in the literature [6]. Magnetic resonance imaging (MRI) is “remarkably unremarkable” in anti-Yo associated PCD although cerebellar atrophy can be seen early in the course of the disease [7, 8]. The negative imaging in anti-Yo positive PCD contrasts PCD associated with other onconeural antibodies, notably anti-Hu but also with anti-Ma2, anti-CV2, and with antibody negative PCD. In such cases PCD occurs in the setting of a more widespread encephalomyelitis and may demonstrate multifocal MRI and functional imaging abnormalities [2, 3, 5]. To date there are no reports demonstrating MRI evidence of cerebellar or extra-cerebellar inflammation in a living patient with anti-Yo associated PCD. A 62 year-old right-handed woman presented with a two-week history of predominantly left-sided limb ataxia, dysarthria and weight loss. Over four weeks in the hospital, her ataxia became generalized with symmetrical limb involvement, horizontal nystagmus, truncal ataxia, and scanning dysarthria. She had normal cognition and no evidence of sensory neuropathy. Initial MRI brain scan was normal. CSF demonstrated a lymphocytic pleocytosis (WBC 9/mm3) and oligoclonal bands. Despite normal serum tumor markers and clear CT imaging of chest, abdomen, and pelvis, Positron Emission Tomography (PET) revealed a hypermetabolic area in the left pelvis, which was subsequently investigated at laparoscopy. Anti-neuronal antibody screening was positive for anti-Yo antibodies and negative for anti Hu, Ri, Ma, Tr and PCA2. A small poorly differentiated ovarian adenocarcinoma was found and bilateral salpingo-oophorectomy performed. A second MRI scan was performed six weeks after onset of symptoms due to clinical deterioration with anti-neuronal antibody status yet unknown. This demonstrated an abnormality in the right medial temporal lobe. This was hyperintense on FLAIR and enhanced with gadolinium (Fig. 1). No cerebellar abnormalities were seen. Following surgical treatment of the tumor, a follow-up scan (at 12 weeks) showed resolution of the medial temporal lobe changes but demonstrated a focal right cerebellar hyperintensity on gadolinium enhanced T1-MRI (Fig. 1). There was no meaningful clinical improvement in her ataxia following surgery and chemotherapy for the tumor. This patient’s case is clinically typical of anti-Yo associated PCD demonstrating a purely cerebellar syndrome with subacute progression resulting in severe disability over 10 weeks. The evolving MRI abnormalities are atypical for the disorder. We believe they represent inflammation. Inflammatory changes have been demonstrated radiologically in other reports of PCD but never in association with anti-Yo [3, 5]. It has been suggested that an inflammatory phase precedes cerebellar atrophy in PCD and that this may even precede clinical presentation [8]. The MRI of the brain was normal at two weeks from symptom presentation. The follow-up scan at six weeks showed right mesial temporal abnormality but no cerebellar change. MRI following resection of the tumor showed resolution of the temporal abnormality but a new focal cerebellitis. No immunosuppressive drugs were given over this period. Although non-inflammatory etiologies such as infection, ischemia, or metastasis could account for the MRI lesions of the cerebellum and temporal lobe in a patient with cancer, the appearance and evolution of this patient’s MRI abnormalities are not consistent with such differentials. Pathologic change in anti-Yo associated PCD is generally restricted to the cerebellum with cortical atrophy and selective Purkinje cell loss. Inflammatory cells may occasionally be seen in the leptomeninges or in the dentate nucleus. In one post mortem study inflammatory changes were noted in the medulla and pons, corresponding to the known expression of the PCA/Yo antigen (a 62 kDa cytoplasmic protein) in cerebellar and brainstem neurons [4, 9]. Therefore it is possible that anti-Yo could be responsible for mesial temporal inflammation. LETTER TO THE EDITORS

Anti-Yo Positive Paraneoplastic Cerebellar Degeneration Associated with Ovarian Carcinoma: Case Report and Review of the Literature

Paraneoplastic cerebellar degeneration (PCD) is a rare nonmetastatic neurological complication in cancer patients. Anti-Yo is one of the anti-onconeural antibodies found in PCD patients. It is believed that anti-Yo occurs almost always in women and is most likely associated with gynecologic or breast cancers, although exceptions exist. Here we report a PCD patient with ovarian cancer having high-titer anti-Yo. The acute onset of her PCD symptoms mimicked that of a stroke. Her ovarian cancer tissue contained abundant plasma cells and lymphocytes. After a thorough review of the literature, we propose a schematic hypothesis for the autoimmune pathogenesis of PCD. Despite anecdotal case reports of neurological improvement with different combinations of treatment, including IVIg, there is still no definitely effective treatment for PCD. Further research on the pathogenesis of PCD may lead to more effective therapies.

Anti-Yo positive paraneoplastic cerebellar degeneration: a report of three cases and review of the literature

Anti-Yo is an anti-Purkiney cell cytoplasmic antibody found in approximately 50% of patients with parancoplastic cerebellar degeneration (PCD). We report three patients with anti-Yo positive PCD (one ovarian carcinoma and two poorly differentiated adenocarcinomas consistent with breast origin). Two were treated with chemotherapy and plasmapheresis but died within months of the diagnosis from progressive neurological disease. The other was given gamma-globulin and has remained table at 6 months follow up. Anti-Yo antibodies are highly specific with almost all patients having breast or gynaecological malignanies. Commonly the tumour is of small volume and asymptomatic. Attempts at treatment are usually unsuccessful but there are a number of reports of stabilisation or improvement when treatment is begun before the development of severe neurological disability. The detection of anti-Yo antibodies is very useful for the diagnosis of PCD allowing early tumour detection and prompt institution of treatment.

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.