Case Of Paraneoplastic Cerebellar Degeneration Research Articles

A Case of Paraneoplastic Cerebellar Degeneration (PCD) in a Patient with Merkel Cell Carcinoma Treated with Nivolumab (P1-14.014)

A Case of Paraneoplastic Cerebellar Degeneration (PCD) in a Patient with Merkel Cell Carcinoma Treated with Nivolumab (P1-14.014)

Anti-Ma2 Antibody Paraneoplastic Cerebellar Degeneration Associated with Renal Cell Carcinoma: A Case Report. (P8-11.013)

<h3>Objective:</h3> To highlight a unique case of Anti-Ma2 antibody paraneoplastic cerebellar degeneration (PCD) associated with renal cell carcinoma (RCC). <h3>Background:</h3> Paraneoplastic neurologic syndromes are a group of immune mediated disorders with a multitude of presentations. PCD is a rare presentation of a rapidly progressive ataxia associated with a variety of antibodies. In 0.5–1% of patients, anti-Ma2 antibody has been known to cause PCD in the setting of neoplasms. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 70-year-old male presented with three-month history of progressive gait difficulty, poor balance and recurrent falls. He had a history of metastatic RCC for which he underwent a total left nephrectomy, radiation therapy and chemotherapy with nivolumab and axitinib. Initial evaluation noted end-gaze nystagmus, limb dysmetria, truncal ataxia and wide-based gait. Chemotherapy was discontinued at the onset of symptoms. Work-up demonstrated cerebellar atrophy and cerebrospinal fluid (CSF) studies revealed mildly elevated protein and oligoclonal bands. He was hospitalized one month later for rapidly worsening ataxia. Repeat serum and CSF studies were positive for anti-Ma2 antibodies. He underwent 5 sessions of plasmapheresis with minimal improvement. Despite treatment, disease continued to progress with patient becoming wheelchair bound. Further treatment with immunotherapies were discussed, but patient elected to pursue palliative care. <h3>Conclusions:</h3> Anti-Ma2 antibodies have been well characterized in PCD in the setting of neoplasms. Immune checkpoint inhibitors (ICI) have also been associated with anti-Ma2 antibodies, causing immune related adverse events including encephalitis and cranial neuropathies. Nivolumab has been reported with cerebellar ataxia in the absence of anti-Ma2 antibodies with symptoms starting shortly after the initiation of therapy. However, symptoms improved after discontinuation of nivolumab and treatment with steroids. In our case, symptoms started almost one year after the initiation of ICI and patient continued to decline even after discontinuation of ICI. This presentation demonstrates a unique case of anti-Ma2 antibody PCD associated with RCC. <b>Disclosure:</b> Dr. Zahra has nothing to disclose. Dr. Ahmed has nothing to disclose. Dr. Sivakumar has nothing to disclose. Dr. Urrea-Mendoza has nothing to disclose. Dr. Veerappan has nothing to disclose.

A Case of Paraneoplastic Cerebellar Degeneration and Autonomic Neuropathy in a Patient with P/Q Type Calcium Channel and CRMP-5 Antibodies and Prostate Adenocarcinoma (P11-1.001)

A Case of Paraneoplastic Cerebellar Degeneration and Autonomic Neuropathy in a Patient with P/Q Type Calcium Channel and CRMP-5 Antibodies and Prostate Adenocarcinoma (P11-1.001)

Paraneoplastic Cerebellar Degeneration Presented as Acute Vertigo

Paraneoplastic cerebellar degeneration is a rare neurological manifestation of nonmetastatic malignancy. Its usual manifestation is subacute to chronic dizziness, gait ataxia, and dysarthria. There have been only a few cases of paraneoplastic cerebellar degeneration with acute presentation. This study describes a patient with paraneoplastic cerebellar degeneration, who presented acute vestibular syndrome and then episodically developed horizontal gaze-evoked nystagmus and gait ataxia.

A Case of Paraneoplastic Cerebellar Degeneration with Anti-Yo Positivity

Paraneoplastic neurological syndrome (PNS) is a neurological picture that occurs in patients with cancer, does not occur with the direct effects of the underlying tumor, cannot be explained by metastasis and side effects of cancer treatment, and is accepted to occur by mechanisms of autoimmune origin. The most common PNS, paraneoplastic cerebellar degeneration (PCD) is a neurological picture that occurs due to autoimmune causes related to breast or gynecological cancers. Before the diagnosis of cancer, the patient may apply with cerebellar complaints and the diagnosis can be reached through autoantibodies such as anti-Yo. Here, a case that presented with PCD before being diagnosed with malignancy and had much better surveillance than known cases in terms of prognosis is presented.

Paraneoplastic Cerebellar Degeneration Associated with Anti-Yo Antibodies Appearing as a Leptomeningeal Cerebellar Carcinomatosis at MRI: a Case Report

Anti-Yo antibodies are the antibodies most frequently identified with paraneoplastic cerebellar degeneration (PCD). They are detected above all in PCD associated with breast and gynaecologic malignancies. Here, we report a third case of PCD with cerebellar contrast enhancement findings at MRI. In fact, AYA cross anti-cerebellar cortex immune reaction leads mainly to hyperintensity signals in T2-weighted MRI sequences, followed by cerebellar atrophy. As such, meningeal contrast enhancement could lead to a diagnostic pitfall as it can be considered a carcinomatosis—above all in serum antibody–negative cases as well as when a metastatic tumour is found. Our patient had no tumoural cells in the cerebrospinal fluid and her neurological syndrome remained stable after immunoglobulin treatment. Anti-Yo antibody serum finding was diriment for PCD diagnosis.

Paraneoplastic cerebellar degeneration in a patient with anti-Yo antibodies and prostate adenocarcinoma

Paraneoplastic cerebellar degeneration is the damage to cerebellar Purkinje cells by anti-Yo antibodies synthesized by the immune system in response to the generation of neuronal proteins by malignant prostate adenocarcinoma cells in 25% of cases. Neurological symptoms of cerebellar lesions appear on average 2 years before cancer manifestation in 70% of patients. During the early stages of the disease, when the tumor cannot be visualized nor clinically manifested, a high titer of anti-Yo antibodies in the cerebrospinal fluid of patients. The presence of anti-Yo antibodies prostate cancer with a clinically latent course was present in 90–98% of patients with cerebellar ataxia. Onconeural autoantibodies (IgG) are well detected in serum by immunoblotting and indirect immunofluorescence. The death of Purkinje cells of the granular and molecular layers of the cerebellar cortex, moderate perivascular lymphocytic infiltration, and further proliferation of microglia lead to atrophy. Inflammatory infiltrates may also be present in the brainstem and cortex, although in significantly less number in compar the cerebellum. This difference accounts for the presence of additional neurological symptoms. The results of the brain MR imaging at the initial stages of paraneoplastic cerebellar degeneration are of little informative value, and degenerative changes in the cerebellum are revealed only a few months later with a subsequent increase in neurological deficit. Removal of malignant tumors leads to the regression of neurological symptoms in 80% of cases. This finding confirms the advisability of a targeted oncological search in patients with symptoms of paraneoplastic cerebellar degeneration and positive onconeural antibodies in the serum. Immunomodulatory therapy, including the use of intravenous immunoglobulin, plasmapheresis, and hormone therapy, is also effective in the treatment of neurological disorders. This paper describes a clinical case of paraneoplastic cerebellar degeneration in a 65-year-old male, with the appearance of neurological symptoms 5 months before the diagnosis of prostate adenocarcinoma. The difficulties of differential diagnosis of this neurological disorder and the course of neurological diseases in the background of tumor removal and conducted immunotherapy are discussed.

PARANEOPLASTIC DAMAGE TO THE CENTRAL AND PERIPHERAL NERVOUS SYSTEM IN BREAST CANCER: A CASE REPORT

Paraneoplastic neurological syndrome involves the concurrent development of cancer and neurologicaldiseases. Breast cancer is the second most common cancer associated with paraneoplastic damage to the central and peripheral nervous system. Autoimmune genesis of the disease is characterized by the presence of highly specific onconeural antibodies, which selectively affect neurons in the brain cord, spinal cord and spinal ganglia, and cause the onset of neurological symptoms within 2 years before cancer is detected. Six well-characterized onconeural antibodies detected in the blood serum of breast cancer patients can be used for the laboratory diagnosis of paraneoplastic neurological syndrome. Of them, anti-Hu, anti-CV2 and anti-amphiphysin antibodies cause polyneuropathy most often. Anti-Yo antibody is usually associated with cerebellar degeneration. Multiple neuronal autoantibodies can be simultaneously detected in a patient. Removal of the tumor may lead to stabilization and even partial regression of the neurological symptoms in 70 % of patients. Therefore, the surgical treatment of cancer should consider not only the tumor extension, but also the severity and progression of neurological deficit. We present a case of paraneoplastic cerebellar degeneration and paraneoplastic polyneuropathy in a 50-year-old woman with the neurological symptoms appeared 5 months before breast infiltrating ductal carcinoma was detected. The current approaches to the diagnosis of paraneoplastic neurological syndrome, as well as feasibility of radical removal of the tumor due to progression of neurological deficit were discussed.

Paraneoplastic Cerebellar Degeneration: A Rare but Important Consideration

Paraneoplastic cerebellar degeneration is an uncommon autoimmune disorder characterized clinically by progressive, ultimately incapacitating ataxia and pathologically by destruction of cerebellar Purkinje cells, with variable loss of other cell populations. The paraneoplastic cerebellar degeneration can antedate the recognition of malignancy and hence can be a warning sign for occult tumor. We are reporting two cases of paraneoplastic cerebellar degeneration that presented before any evidence of tumor and later developed advanced stage of malignancy not amenable for surgery.

Occult Breast Carcinoma Presenting With Anti-Ri-Associated Paraneoplastic Cerebellar Degeneration Revealed With FDG-PET

Paraneoplastic neurological syndromes are rare diseases affecting less than 0,01 % of the cancerous patients. Here, we present a rare case of paraneoplastic cerebellar degeneration with anti-Ri antibodies as the presenting manifestation of an occult breast cancer. Our observation emphasizes the importance of the nature of the anti-neuronal antibody and the fluorodeoxyglucose-positron emission tomography to make a definitive diagnosis in patients with subactue onset of neurological deficit suggesting paraneoplastic cerebellar degeneration.

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.

Paraneoplastic cerebellar degeneration associated with noncutaneous Merkel cell carcinoma.

Paraneoplastic cerebellar degeneration (PCD) is a rare condition that often heralds an underlying tumor. The syndrome is often associated with small cell carcinoma of the lung, breast cancer, gynecologic cancers, and Hodgkin disease. Treatment options are not well defined and improvement is often limited. Diagnosis can often be aided by detection of antibodies to various cerebellar proteins, including Yo, voltage-gated calcium channels (VGCC), and the Delta/Notch-like epidermal growth factor–related receptor (the target antigen of the Tr immune response). Current therapeutic goals are aimed at suppression or removal of immune-mediated activity, resection of primary tumor, and symptomatic treatment. We report a case of PCD with VGCC autoantibodies and noncutaneous metastatic Merkel cell carcinoma.

A Case of Paraneoplastic Cerebellar Degeneration Associated with Non-Cutaneous Metastastic Merkel Cell Carcinoma (P1.036)

A Case of Paraneoplastic Cerebellar Degeneration Associated with Non-Cutaneous Metastastic Merkel Cell Carcinoma (P1.036)

Paraneoplastic Cerebellar Degeneration Associated with Gynecological Malignancy: Two Contrasting Case Reports

Paraneoplastic cerebellar degeneration is a rare neurologic disorder associated with several forms of cancer, including gynecological. It may present months or years prior to or after the diagnosis of cancer. Recognition of the condition is paramount for early diagnosis of the underlying malignancy and/or for mitigating the permanent effects of the cerebellar degeneration. We present two cases of paraneoplastic cerebellar degeneration associated with gynecological malignancies which illustrate the varied timings of presentation and outcomes of the disorder.

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.

Anti-Yo Antibody-mediated Paraneoplastic Cerebellar Degeneration in a Female Patient with Pleural Malignant Mesothelioma

Paraneoplastic cerebellar degeneration is a rare non-metastatic complication of malignancies. It presents with acute or subacute onset of ataxia, dysarthria and intention tremor. Paraneoplastic cerebellar degeneration is most commonly associated with malignancies of the ovary, breast and lung. The anti-Yo (anti-Purkinje cells) antibodies that specifically damage the Purkinje cells of the cerebellum are found in the serum and cerebrospinal fluid. Anti-Yo-related paraneoplastic cerebellar degeneration is most commonly found in women with gynecological and breast cancers, but it is reported in other malignancies. Patients with paraneoplastic syndromes most often present with neurologic symptoms before an underlying cancer is detected. We report a case of anti-Yo-related paraneoplastic cerebellar degeneration associated with pleural malignant mesothelioma in a 51-year-old female patient. She presented to our department with a 2-week history after the last chemotherapy of progressive dizziness related to head movement, nausea, vomiting, ataxia and unsteady gait. A western blot assay was negative for anti-Hu, anti-Ri, anti-Ma2, anti-CV2 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. In conclusion, we report a case of paraneoplastic cerebellar degeneration in a patient with pleural malignant mesothelioma because of the rarity of this neurologic presentation after the diagnosis of malignant mesothelioma and of the association with anti-Yo antibodies.

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.

Isolated &lt;emph type="ital"&gt;ZIC4&lt;/emph&gt; Antibodies in Paraneoplastic Cerebellar Syndrome With an Underlying Ovarian Tumor

To describe a patient with paraneoplastic cerebellar syndrome and the uncommon association of isolated ZIC4 antibodies and ovarian cancer. Case report and review of the literature. Hospitalized care, follow-up in private practice. A 60-year-old woman with severe paraneoplastic cerebellar syndrome and an underlying ovarian adenocarcinoma. Neurological examination, lumbar puncture, laboratory tests, radiological imaging, and histological examination. Clinical course and titer of anti- ZIC4 antibodies in serum. Laboratory and cerebrospinal fluid tests revealed the isolated presence of ZIC4 antibodies. Screening results for small cell lung carcinoma were negative, while abdominal computed tomographic scan was suggestive of ovarian adenocarcinoma, which was confirmed by histological examination. Glucocorticosteroid administration and chemotherapy led to complete remission of paraneoplastic cerebellar degeneration. To the best of our knowledge, this is the first case of paraneoplastic cerebellar degeneration in a patient with isolated ZIC4 antibodies associated with ovarian adenocarcinoma.

CD8 positive T-cell infiltration in the dentate nucleus of paraneoplastic cerebellar degeneration

Recent reports have discussed the presence of cytotoxic T cells in paraneoplastic cerebellar degeneration (PCD). We report an autopsy case of PCD associated with anti-Hu antibody, in which we revealed infiltration of CD8+ T cells in and around the dentate nucleus but not in the cerebellar cortex, in addition to severe Purkinje cell loss. Some infiltrated mononuclear cells expressed cytotoxic cell marker, Granzyme B. Decrease of neurons and reduced presynapses were demonstrated in the dentate nucleus. This is the first report that suggests the possibility of the dentate nucleus being primarily attacked followed by Purkinje cell loss in PCD.

Paraneoplastic syndrome in vaginal melanoma: a case report and review of the literature

The authors of this article present a case of a woman diagnosed with a vaginal melanoma who developed paraneoplastic syndrome (PNS) soon after diagnosis. A review of the literature regarding PNSs in gynecological malignancies is also described in this article. To our knowledge, this is the first reported case of paraneoplastic cerebellar degeneration with opsoclonus myoclonus secondary to a vaginal melanoma. In addition, our patient had an unusually acute progression to pancerebellar symptoms over the course of 3 weeks. Her paraneoplastic symptoms improved significantly after partial resection of the melanoma.