Paraneoplastic Cerebellar Degeneration Patients Research Articles

A Case Report of Complex Korean Medicine Treatment Including Modified Gamiguibi-tang in a Paraneoplastic Cerebellar Degeneration Patient with Dysarthria and Weakness of Distal Extremity

Objectives: This study investigated the treatment response to Korean medicine of a paraneoplastic cerebellar degeneration (PCD) patient with dysarthria and weakness of distal extremity.Case presentation: A 53-year-old female diagnosed with PCD complained of dysarthria and weakness of distal extremity. During 32-day hospitalization, she was treated with Korean medicine, namely, herbal medicine (modified Gamiguibi-tang), acupuncture (15 minutes twice a day at CV23, HT7, LI4, LR3, ST36, SP6, GB20, TE17, PC6, GV20, Ex-HN1, GV24 etc.), moxibustion, and cupping, combined with Western medicine (prednisolone, azathioprine) and physical therapy. Post-treatment, the patient global assessment (PGA) score of dysarthria fell from 100 to 60; grasp power rose from 15 kg to 19 kg and 13 kg to 17 kg in the right and left hands, respectively; and the 5-level EQ-5D version (EQ-5D-5L), EQ visual analogue scale (EQ-VAS), and Beck depression inventory (BDI-II) scores changed from 10 to 8, 0 to 80, and 34 to 7 respectively. Follow-up visits continued for about a month after discharge, improvement in symptoms maintained, and there were no significant side effects.Conclusions: Given the lack of standard treatment for PCD, Korean medicine can be tried clinically for the treatment of PCD patients with dysarthria and weakness of distal extremity. However, further studies with control groups are needed.

Paraneoplastic cerebellar degeneration

Introduction. Paraneoplastic cerebellar degeneration (PCD) is an immune-mediated and rapidly progressive cerebellar syndrome that develops as a result of a cross-immune response to the common antigens for the tumor and cerebellar cells. Timely diagnosis and treatment of PCD improves the functional status and survival of these patients.Objective. To analyze the clinical, laboratory and neuroimaging characteristics of PCD case series in comparison with literature data.Material and methods. 16 patients with PCD (13 women, 3 men) were examined. An assessment of the clinical presentation, brain MRI study, blood and cerebrospinal fl uid laboratory tests were carried out, the data of cancer search and patients follow-up were analyzed.Results. The median age of PCD patients was 55 years, the duration of the disease was 8.5 months (range 4 to 16 months). In 12 patients, PCD was the fi rst manifestation of cancer. The clinical prentation was presented by rapidly progressive cerebellar ataxia, often in combination with oculomotor disturbances, pyramidal and bulbar syndrome, hand tremor and dystonia. An associated cancers were detected in 13 patients (81%). Antineuronal antibodies were found in 14 patients (88%): anti-Yo-1, antibodies to amphiphysin, anti-Hu, anti-CV2 and anti-GAD. Mild atrophic changes of the cerebellum were found in 6 patients, and in 2 cases cerebellar hemiatrophy was observed.Conclusion. PCD is a rare disabling but potentially curable disease. The basis of diagnosis is the analysis of the clinical presentation and neuroimaging data, the detection of antineuronal antibodies and in fl ammatory changes in the cerebrospinal fl uid, as well as a thorough cancer search.

A cerebellar degeneration-related protein 2-like cell-based assay for anti-Yo detection in patients with paraneoplastic cerebellar degeneration.

Commercially available tests for Yo antibody detection have low specificity for paraneoplastic cerebellar degeneration (PCD) because these assays use cerebellar degeneration-related protein 2 (CDR2) as the antigen, not CDR2-like (CDR2L). We aimed to test the hypothesis that use of a CDR2L cell-based assay (CBA), as an additional screening technique, would increase the accuracy of Yo-PCD diagnosis. An in-house CBA to test for anti-CDR2L antibodies was developed and used to screen sera from 48 patients with confirmed anti-Yo-associated PCD. Fifteen non-Yo PCD patients, 22 patients with ovarian cancer without neurological syndromes, 50 healthy blood donors, 10 multiple sclerosis, 15 Parkinson's disease, and five non-paraneoplastic ataxic patients were included as controls. Sera were also tested by western blot analysis using recombinant CDR2 and CDR2L proteins developed in house, by the commercially available line immunoassays from Ravo Diagnostika and Euroimmun, and by the CDR2 CBA from Euroimmun. The CDR2L CBA identified all 48 patients with Yo-PCD. No CDR2L CBA reaction was observed in any of the control sera. The western blot technique had lower sensitivity and specificity as sera from eight and six of the 48 Yo-PCD patients did not react with recombinant CDR2 or CDR2L, respectively. The CDR2L CBA is highly reliable for identification of Yo-PCD. Although our findings indicate that, currently, the combination of CDR2 and CDR2L yields the most reliable test results, it remains to be evaluated if a test for single anti-CDR2L positivity will serve as a sufficient biomarker for Yo-PCD diagnosis.

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.

GRP78 antibodies damage the blood-brain barrier and relate to cerebellar degeneration in Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction caused by autoantibodies binding to P/Q-type voltage-gated calcium channels. Breakdown of the blood-brain barrier and diffusion of cerebellar granule/Purkinje cell-reactive autoantibodies into the CNS are critical for the pathogenesis of paraneoplastic cerebellar degeneration (PCD) with Lambert-Eaton myasthenic syndrome. We recently found evidence that glucose-regulated protein 78 (GRP78) autoantibodies in the plasma of patients with neuromyelitis optica promote the CNS access of AQP4 autoantibodies. In the present study, we investigated whether the GRP78 autoantibodies in PCD-LEMS IgG boost the brain uptake of cerebellar cell-reactive antibodies across the blood-brain barrier and facilitate cerebellar dysfunction. We first evaluated the effects of purified IgG from PCD-LEMS or PCD patients on the blood-brain barrier function in human brain microvascular endothelial cells using a high content imaging system with nuclear factor κB p65 and intracellular adhesion molecule 1 (ICAM1) immunostaining. Next, we identified GRP78 autoantibodies causing blood-brain barrier permeability in PCD-LEMS IgG by co-immunoprecipitation and the living cell-based antibody binding assays. Exposure of brain microvascular endothelial cells to IgG from PCD-LEMS patients induced nuclear factor κB p65 nuclear translocation, ICAM1 upregulation, reduced claudin-5 expression, increased permeability and increased autocrine IL-1β and IL-8 secretion; the IgG from patients with Lambert-Eaton myasthenic syndrome did not have these effects. We detected GRP78 autoantibodies in the IgG of LEMS-PCD (83.3%, n = 18), but observed fewer in patients with LEMS (6.6%, n = 15) and none were observed in the control subjects (n = 8). The depletion of GRP78 autoantibodies reduced the biological effect of LEMS-PCD IgG on brain microvascular endothelial cells. These findings suggest that GRP78 autoantibodies play a role beyond neuromyelitis optica and that they have direct implications in the phenotypic differences between PCD-LEMS and LEMS.

CDR2L Is the Major Yo Antibody Target in Paraneoplastic Cerebellar Degeneration.

The pathogenesis of Yo-mediated paraneoplastic cerebellar degeneration (PCD) is unclear. We applied cerebrospinal fluid and serum from PCD patients as well as CDR2 and CDR2L antibodies to neuronal tissue, cancer cell lines, and cells transfected with recombinant CDR2 and CDR2L to elucidate which is the major antigen of Yo antibodies. We found that Yo antibodies bound endogenous CDR2L, but not endogenous CDR2. However, Yo antibodies can bind the recombinant CDR2 protein used in routine clinical testing for these antibodies. Because Yo antibodies only bind endogenous CDR2L, we conclude that CDR2L is the major antigen of Yo antibodies in PCD. ANN NEUROL 2019;86:316-321.

Paraneoplastic cerebellar degeneration: Yo antibody alters mitochondrial calcium buffering capacity

AimNeurodegeneration is associated with dysfunction of calcium buffering capacity and thereby sustained cellular and mitochondrial calcium overload. Paraneoplastic cerebellar degeneration (PCD), characterized by progressive Purkinje neurone degeneration following paraneoplastic Yo antibody internalization and binding to cerebellar degeneration‐related protein CDR2 and CDR2L, has been linked to intracellular calcium homeostasis imbalance due to calbindin D28k malfunction. Therefore, we hypothesized that Yo antibody internalization affects not only calbindin calcium binding capacity, but also calcium‐sensitive mitochondrial‐associated signalling, causing mitochondrial calcium overload and thereby Purkinje neurone death.MethodsImmunohistochemically, we evaluated cerebellar organotypic slice cultures of rat brains after inducing PCD through the application of Yo antibody‐positive PCD patient sera or purified antibodies against CDR2 and CDR2L how pharmacologically biased mitochondrial signalling affected PCD pathology.ResultsWe found that Yo antibody internalization into Purkinje neurons caused depletion of Purkinje neurone calbindin‐immunoreactivity, cannabinoid 1 receptor over‐activation and alterations in the actions of the mitochondria permeability transition pore (MPTP), voltage‐dependent anion channels, reactive oxygen species (ROS) and Na+/Ca2+ exchangers (NCX). The pathological mechanisms caused by Yo antibody binding to CDR2 or CDR2L differed between the two targets. Yo‐CDR2 binding did not alter the mitochondrial calcium retention capacity, cyclophilin D‐independent opening of MPTP or activity of NCX.ConclusionThese findings suggest that minimizing intracellular calcium overload toxicity either directly with cyclosporin‐A or indirectly with cannabidiol or the ROS scavenger butylated hydroxytoluene promotes mitochondrial calcium homeostasis and may therefore be used as future neuroprotective therapy for PCD patients.

Antibodies to a brain‐type creatine kinase associated with paraneoplastic neurological syndromes

AbstractBackgroundPreviously, we identified a brain‐type creatine kinase antibody to be associated with paraneoplastic cerebellar degeneration using a proteomic approach. Immunohistochemistry showed that this antibody reacted with both mouse cerebellar neurons and bladder cancer tissues. Furthermore, we detected this antibody in sera from two paraneoplastic cerebellar degeneration patients with small cell lung cancer and one lymphoma patient. In total, we detected four paraneoplastic cerebellar degeneration patients.AimTo confirm the new onconeural antibody, we investigated whether this autoantigen is expressed in both human cerebellum and cancer tissues (small cell lung cancer of lymphoma).MethodsWe examined sera from two paraneoplastic cerebellar degeneration patients with small cell lung cancer, one lymphoma patient and a patient with sensory‐motor neuropathy as paraneoplastic neurological syndrome by western blotting and enzyme‐linked immunosorbent assay to explore creatine kinase brain‐type antibody expressions in these cancer cells as well as in the human cerebellum. Sera from the patients without paraneoplastic cerebellar degeneration were used as controls. In addition, we examined the serum from a patient with sensory‐motor neuropathy as paraneoplastic neurological syndrome by western blot.ResultsThe mean serum values of creatine kinase brain‐type antibodies in paraneoplastic cerebellar degeneration patients with small cell lung cancer were significantly higher than those of small cell lung cancer patients without paraneoplastic cerebellar degeneration. Immunohistochemistry detected this autoantigen expression in both abovementioned specimens. We also detected this antibody in the serum in sensory‐motor neuropathy as paraneoplastic neurological syndrome.ConclusionOur study showed that this antibody was produced in four paraneoplastic cerebellar degeneration patients, and that this autoantigen expression was evident in human cerebellum and cancer. These findings show that creatine kinase brain‐type antibody might be a novel antibody associated with paraneoplastic neurological syndrome.

Paraneoplastic cerebellar degeneration as the first evidence of malignancy: A case report

Paraneoplastic cerebellar degeneration (PCD) is an immune-mediated paraneoplastic disorder affecting the cerebellum. PCD associated with ovarian malignancy is a rare occurrence with fewer than 100 cases reported in published work. PCD patients express anti-Yo antibody, one of the anti-onconeuronal antibodies which is most likely associated with gynecologic or breast malignancies. In this report, we present the case of a 65-year-old postmenopausal woman presenting with acute symptoms of PCD as a first sign of ovarian malignancy.

Paraneoplastic cerebellar degeneration associated with an onconeural antibody against creatine kinase, brain-type

Onconeural immunity, a cancer-stimulated immune reaction that cross-reacts with neural tissues, is considered to be the principal pathological mechanism for paraneoplastic neurological syndromes (PNS). A common PNS is paraneoplastic cerebellar degeneration (PCD). We had encountered a PCD patient with urothelial carcinomas (UC) of the urinary bladder who was negative for the well-characterized PNS-related onconeural antibodies. In the present study, we aimed to identify a new PCD-related onconeural antibody, capable of recognizing both cerebellar neurons and cancer tissues from the patient, and applied a proteomic approach using mass spectrometry. We identified anti-creatine kinase, brain-type (CKB) antibody as a new autoantibody in the serum and cerebrospinal fluid from the patient. Immunohistochemistry indicated that anti-CKB antibody reacted with both cerebellar neurons and UC of the urinary bladder tissues. However, anti-CKB antibody was not detected in sera from over 30 donors, including bladder cancer patients without PCD, indicating that anti-CKB antibody is required for onset of PCD. We also detected anti-CKB antibody in sera from three other PCD patients. Our study demonstrated that anti-CKB antibody may be added to the list of PCD-related autoantibodies and may be useful for diagnosis of PCD.

Anti-purkinje cell and natural autoantibodies in a group of psychiatric patients. Evidences for a correlation with the psychopathological status.

Phenomena of autoimmunity are frequent among psychiatric patients, but we don’t know yet if they should be considered primary and linked to the pathophisiology of the disorder, or aspecific and associated to a general immune system activation. Paraneoplastic Cerebellar Degeneration (PCD) represents a well known model of specific autoimmunity. In order to better understand the abovementioned issues, we used this condition to compare a set of immune dysfunctions found in a group of psychiatric patients. For this reason we tested sera from 48 psychiatric patients (24 schizophrenics, 17 bipolars and 7 obsessive-compulsive), 22 PCD patients and 52 healthy controls for the presence of anti-Purkinje autoantibodies and of some natural autoantibodies (ANAs, AMAs, APCAs, ASMAs). Psychopatological status of the psychiatric patients was assessed with BPRS, SANS, SAPS, HAM-D, CGI-S. In the psychiatric group anti-Purkinje autoantibodies were identified in 11/48 (22,9%) patients, while they were present in 22/22 (100%) PCD patients and in 0/52 (0%) healthy controls. Among all anti-Purkinje autoantibody positive patients (in the PCD and psychiatric samples), only those belonging to the psychiatric sample, but not those with PCD, were frequently found positive also for natural autoantibodies, that are considered good markers of aspecific immune activation. In these patients, both anti-Purkinje and natural autoantibodies were found associated with acute/positive psychopathological symptoms. These results seem to point out that some phenomena of auto-immunity described in psychiatric patients could be aspecific, unrelated to the pathophysiology of the concomitant mental disorders and could be more frequent during phases of acute/positive symptoms.

ZIC antibodies in paraneoplastic cerebellar degeneration and small cell lung cancer

Patients with isolated ZIC4 antibodies usually have paraneoplastic cerebellar degeneration (PCD) and small cell lung cancer (SCLC) but the frequency is unknown. We analyzed the presence of ZIC1, ZIC2 and ZIC4 antibodies in 27 patients with PCD and SCLC negative for other onconeural antibodies. ZIC antibodies were detected in nitrocellulose filters with phage plaques. Four (15%) PCD sera recognized ZIC2. Three of these positive sera also reacted with ZIC1 and two with ZIC4. Our study suggests that 1) the incidence of isolated ZIC antibodies is low in PCD patients and SCLC and 2) ZIC antibodies are probably directed to epitopes shared by the three ZIC proteins.

Functional analysis of CD8 + T cell responses to the onconeural self protein cdr2 in patients with paraneoplastic cerebellar degeneration

Paraneoplastic cerebellar degeneration (PCD) is linked to an immune response against cerebellar degeneration related antigen 2 (cdr2) co-expressed in tumor and Purkinje neurons. Here, comprehensive immune-assessment assays were used to analyze CD8 + T cells from 7 PCD patients, but no evidence was found of CD8 + T cells specific for either of two previously described cdr2 epitopes (cdr2-1 and cdr2-2). In contrast, viral-specific CD8 + T cells from healthy volunteers and PCD patients were measurable. These findings are inconsistent with an obligate role for cdr2-1- or cdr2-2-specific CD8 + T cells in the pathogenesis of PCD.

A T cell receptor associated with naturally occurring human tumor immunity

The onconeural antigens appear to serve as tumor rejection antigens in the paraneoplastic neurologic disorders. Here, we used an unbiased peptide binding screen, followed by studies in HLA-A2.1 transgenic mice to identify naturally processed HLA-A2.1 restricted epitopes of the paraneoplastic cerebellar degeneration breast/ovarian cancer antigen cdr2. These mice were used to clone high-avidity cdr2-specific CD8(+) T cells that recognize human tumor cells presenting endogenously loaded MHC class I-cdr2 peptide. T cells with this specificity were detected in the peripheral blood of two HLA-A2.1(+) paraneoplastic cerebellar degeneration patients. We cloned T cell receptor (TCR) alpha and beta genes from cdr2-specific T cells; electroporation of RNA encoding this TCR turned nonreactive donor T cells into efficient killers of human cdr2-expressing tumor cells. Cloned cdr2-specific TCR genes provide a clinically relevant means for immunologic targeting of human gynecologic cancers.

Detection and treatment of activated T cells in the cerebrospinal fluid of patients with paraneoplastic cerebellar degeneration

Patients with paraneoplastic cerebellar degeneration (PCD) offer the opportunity to explore the mechanisms underlying tumor immunity and immune-mediated neuronal degeneration. Cytotoxic T lymphocytes (CTLs) specific for the PCD onconeural antigen cdr2 found in the blood of patients with PCD are likely to be effectors of PCD tumor immunity. Here, we suggest a role for CTLs in the autoimmune destruction of Purkinje neurons. More than 75% of the cells obtained from the cerebrospinal fluid (CSF) of PCD patients were CD3+ alphabeta T cells. In patients with active/progressive disease, 20% to 40% of CSF cells were activated T cells, and the CD4+ helper cells were Th1-type cells. Three PCD patients were given tacrolimus, a specific inhibitor of activated T cells, which markedly reduced these cells in the CSF. Tacrolimus also reduced the number of activated cdr2-specific CTLs in the peripheral blood, but did not lead to tumor recurrence. We suggest that activated cdr2-specific CTLs in the CSF contribute to Purkinje degeneration in PCD, and that tacrolimus therapy may benefit patients with paraneoplastic neurological disease and other T cell-mediated autoimmune neurological disorders.

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.

Cytotoxic T cells against a peptide of Yo protein in patients with paraneoplastic cerebellar degeneration and anti-Yo antibody.

Anti-Yo antibodies are present in the sera and cerebrospinal fluid of some patients with paraneoplastic cerebellar degeneration (PCD), but there is no evidence that the presence of anti-Yo antibodies causes the Purkinje cell loss seen in PCD patients. We examined the level of cytotoxic T lymphocyte (CTL) activity against a nine-amino acid peptide of the Yo protein using the Human Leukocyte Antigen- (HLA-) based approach called reverse immunogenetics. Mononuclear cells (MNCs) were isolated from the peripheral venous blood and fibroblasts were obtained from the skin of three patients with PCD with anti-Yo antibody. After activating the MNCs of the three patients with the peptide, it showed CTL activity against the Yo protein peptide expressed on autologous fibroblasts. Therefore, CTLs may be involved in the loss of Purkinje cells in PCD.

The cytoplasmic Purkinje onconeural antigen cdr2 down-regulates c-Myc function: implications for neuronal and tumor cell survival.

Paraneoplastic cerebellar degeneration (PCD) is a disorder in which breast or ovarian tumors express an onconeural antigen termed cdr2, which normally is expressed in cerebellar Purkinje neurons. This leads to an immune response to cdr2 that is associated with tumor immunity and autoimmune cerebellar degeneration. We have found that cdr2, a cytoplasmic protein harboring a helix-leucine zipper (HLZ) motif, interacts specifically with the HLZ motif of c-Myc. Both proteins colocalize in the cytoplasm of adult cerebellar Purkinje neurons, and coimmunoprecipitate from tumor cell lines and cerebellar extracts. cdr2 down-regulates c-Myc-dependent transcription in cotransfection assays, and redistributes Myc protein in the cytoplasm. Disease antisera from six of six PCD patients specifically blocked the interaction between cdr2 and c-Myc in vitro. These data indicate that cdr2 normally sequesters c-Myc in the neuronal cytoplasm, thereby down-regulating c-Myc activity, and suggest a mechanism whereby inhibition of cdr2 function by autoantibodies in PCD may contribute to Purkinje neuronal death.

Tumor-specific killer cells in paraneoplastic cerebellar degeneration.

Models for immune-mediated tumor regression in mice have defined an essential role for cytotoxic T lymphocytes (CTLs); however, naturally occurring tumor immunity in humans is poorly understood. Patients with paraneoplastic cerebellar degeneration (PCD) provide an opportunity to explore the mechanisms underlying tumor immunity to breast and ovarian cancer. Although tumor immunity and autoimmune neuronal degeneration in PCD correlates with a specific antibody response to the tumor and brain antigen cdr2, this humoral response has not been shown to be pathogenic. Here we present evidence for a specific cellular immune response in PCD patients. We have detected expanded populations of MHC class I-restricted cdr2-specific CTLs in the blood of 3/3 HLA-A2.1+ PCD patients, providing the first description, to our knowledge, of tumor-specific CTLs using primary human cells in a simple recall assay. Cross-presentation of apoptotic cells by dendritic cells also led to a potent CTL response. These results indicate a model whereby immature dendritic cells that engulf apoptotic tumor cells can mature and migrate to draining lymph organs where they could induce a CTL response to tissue-restricted antigens. In PCD, peripheral activation of cdr2-specific CTLs is likely to contribute to the subsequent development of the autoimmune neuronal degeneration.

Absence of anti-P/Q calcium channel antibody in the sera of patients with anti-Yo antibody-positive paraneoplastic cerebellar degeneration.

Subacute cerebellar ataxia in patients with cancer in whom metastasis to the cerebellum has not occurred and who exhibit neither infection, side effects of chemotherapy, nor nutritional deficiencies, is designated paraneoplastic cerebellar degeneration (PCD). A group of women with PCD and ovarian or uterine cancer harbor an anti-Yo antibody in their sera and CSF.1 Anti-Yo antibody binds to 52- to 62-kD and 34-kD proteins on Western blots of human Purkinje cell extracts and reacts with Purkinje and other neuronal cell cytoplasm on immunohistochemical analysis. This antibody may be produced against tumor antigens that also react with neuronal proteins. However, there is no evidence that anti-Yo antibody causes neuronal damage. We have failed in numerous attempts to produce animal models of PCD by injection of serum IgG from patients with PCD into rodent brains or by immunization of rodents with recombinant Yo protein; neuronal degeneration was not induced in any of these cases.2 However, the sera of PCD patients could contain minor antibodies …