anti-Yo Antibodies Research Articles

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.

JS1.1 Specific genetic alterations of breast tumors lead to Yo paraneoplastic cerebellar syndromes

Abstract BACKGROUND Paraneoplastic cerebellar degenerations with anti-Yo antibodies (Yo-PCD) are rare syndromes associated with ovarian or breast cancers and caused by an auto-immune response against neuronal antigens expressed by tumor cells. We previously demonstrated in Yo-PCD ovarian cancers an association between massive infiltration of ovarian tumors by activated immune effector cells and recurrent gains and/or mutations of onconeural Yo genes (CDR2L and CDR2), suggesting that such genetic alterations in ovarian tumor cells may trigger immune tolerance breakdown and initiation of the auto-immune reaction against Purkinje cells. MATERIAL AND METHODS We pursued the characterization of Yo-PCD tumors and specifically studied breast cancer by IHC, FISH, CGH array and RNA sequencing analysis of 17 breast Yo-PCD tumors and by comparing their genetic characteristics with 10 sporadic breast tumors and public databases. RESULTS We confirmed that specific genetic alterations were also present in breast cancers associated with Yo-PCD. Moreover, this study provides additional evidence for a role of tumor cell specificities in PCD immunopathology by revealing peculiarities in Yo-PCD breast tumors compared to Yo-PCD ovarian cancer. Indeed, not only the CDR2L Yo gene was amplified in 8/9 breast Yo-PCD cancers but also the Erb2/Her2 gene in 15/16 (both genes are on chromosome 17q). In addition to this original Her2 and Yo antigen amplification confirmed by FISH, we observed an overexpression of these proteins by IHC analysis. These Yo-PCD breast cancers are also all negative for hormone receptors (HR). Thus, Yo-PCD breast tumors seem to belong to the molecularly and clinically distinct class of HR-negative and Her2-enriched breast cancers, which represents less than 10 % of breast cancers in the general population. Transcriptomic analysis confirmed that breast Yo-PCD tumors differ by their expression programs from classical breast cancers molecular subtypes. CONCLUSION Understanding the tumor genetic features leading to the immune breakdown and anti-tumor immune response as well as nervous tissue attack remains challenging and seems to be specific according to the tumor subtypes. Herein, our results suggest that, despite sharing common genetic alterations (copy number variations and mutations affecting Yo genes), the Yo-PCD immunopathogenesis of breast and ovarian cancers differ by involving different tumor-specific molecular pathways.

PARANEOPLASTIC CEREBELLAR DEGENERATION (PCD) IN EXTENSIVE STAGE SCLC IN REMISSION

SESSION TITLE: Lung Cancer 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: PCD in the setting of small cell lung cancer (SCLC) is a rare association with less than 300 cases reported at the time of diagnosis and not when in remission. The common presenting symptoms and signs are diplopia, gait instability, scanning speech, intentional tremors, nystagmus, dysdiadochokinesia and pendular knee jerk. Causes of cerebellar signs in malignancy are tumor invasion, compression and PCD. Here a case is described of PCD in extensive stage SCLC post therapy in clinical and radiological remission. Literature review does not identify a similar case. CASE PRESENTATION: 58 year old male with extensive stage small cell lung cancer with brain metastases diagnosed a year ago, received six cycles of carboplatin and etoposide and cranial radiation. Radiological imaging after the therapy did not show any evidence of residual disease. Post-therapy imaging established remission. Subsequent to this imaging patient developed decline in his ability to walk, slurring of speech, double vision, nausea and vomiting. Cerebellar signs including diplopia, nystagmus, intentional tremor, past pointing, dysdiadochokinesia were noted. PET scan did not show any new lesions, CSF analyses showed elevated protein with no tumor cells and serology for PCD showed indeterminate results for anti-YO antibodies. Plasma exchange (PEX) was initiated and continued for five sessions. Clinically significant improvement in cerebellar signs after the completion of therapy was noted. DISCUSSION: PCD is associated with ovarian, lung, lymphoma, breast, uterine, colon and sarcoma. Two sub types of PCD are anti-YO positive and anti-YO negative. Diagnosis of PCD is an early indication of tumor progression or presence of occult malignancy. Treatment of PCD include managing cerebellar degeneration and treating malignancy. Treatment options for PCD include IVIG and plasmapheresis. Steroids can be used as an adjunctive therapy. A treated patient with extensive stage small cell cancer in remission presenting with PCD is reported. CONCLUSIONS: Diagnosis of PCD is an early indication of tumor progression or presence of occult malignancy. Even though there was no residual lesions found on presentation, periodic surveillance for relapse is recommended. Reference #1: J Neurol Neurosurg Psychiatry. 2006 Apr; 77(4): 562–563. https://doi.org/10.1136/jnnp.2005.073379 Reference #2: Mayo Clin Proc. 1990 Nov;65(11):1423-31 DISCLOSURES: No relevant relationships by koyamangalath krishnan, source=Web Response No relevant relationships by Nagaishwarya Moka, source=Web Response No relevant relationships by Sakshi Singal, source=Web Response

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.

Paraneoplastic cerebellar degeneration associated with cerebellar hypermetabolism

Rationale:Paraneoplastic cerebellar degeneration (PCD) is an immune-mediated neurological deficit affecting the cerebellum. Anti-Yo antibody positive PCD is a rare occurrence most likely associated with gynecologic or breast malignancies. The identification of the underlying tumor is a diagnostic challenge in many of these patients.Patient concerns:We present a 68-year-old woman with acute symptoms of PCD as a first sign of underlying occult malignancy. Further investigation revealed a positive anti-Yo antibody. Although brain magnetic resonance imaging (MRI) was unremarkable, positron emission tomography (PET)/computed tomography (CT) revealed intense hypermetabolism of cerebellum and diffused hypometabolism in the rest of brain. On 1-year follow-up, despite the primary malignancy is still unknown, her symptoms improved significantly after immunotherapy.Diagnoses:Paraneoplastic cerebellar degeneration.Interventions:The patient was given IV methylprednisolone 500 mg once a day for 5 consecutive days, followed by oral prednisone 60 mg once a day for 3 months.Outcomes:The patient's symptoms were gradually improved during the hospitalization period. On one year follow up, she was able to walk independently and perform some simple tasks.Lessons:Cerebellar hypermetabolism in PCD suspected patients may help confirming the diagnosis in an earlier stage and may predict a better outcome after immunotherapy.

Genetic alterations and tumor immune attack in Yo paraneoplastic cerebellar degeneration.

Paraneoplastic cerebellar degenerations with anti-Yo antibodies (Yo-PCD) are rare syndromes caused by an auto-immune response against neuronal antigens (Ags) expressed by tumor cells. However, the mechanisms responsible for such immune tolerance breakdown are unknown. We characterized 26 ovarian carcinomas associated with Yo-PCD for their tumor immune contexture and genetic status of the 2 onconeural Yo-Ags, CDR2 and CDR2L. Yo-PCD tumors differed from the 116 control tumors by more abundant T and B cells infiltration occasionally organized in tertiary lymphoid structures harboring CDR2L protein deposits. Immune cells are mainly in the vicinity of apoptotic tumor cells, revealing tumor immune attack. Moreover, contrary to un-selected ovarian carcinomas, 65% of our Yo-PCD tumors presented at least one somatic mutation in Yo-Ags, with a predominance of missense mutations. Recurrent gains of the CDR2L gene with tumor protein overexpression were also present in 59% of Yo-PCD patients. Overall, each Yo-PCD ovarian carcinomas carried at least one genetic alteration of Yo-Ags. These data demonstrate an association between massive infiltration of Yo-PCD tumors by activated immune effector cells and recurrent gains and/or mutations in autoantigen-encoding genes, suggesting that genetic alterations in tumor cells trigger immune tolerance breakdown and initiation of the auto-immune disease.

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.

Paraneoplastic cerebellar syndromes associated with antibodies against Purkinje cells

ABSTRACTThe paraneoplastic cerebellar syndrome presents as severe neuroimmunological disease associated with malignancies. Antibodies against antigens expressed by tumor cells cross-react with proteins of cerebellar Purkinje cells leading to neuroinflammation and neuronal loss. These antineuronal antibodies are preferentially investigated by serological analyses while examination of the cerebrospinal fluid is only performed infrequently.We retrospectively investigated 12 patients with antineuronal antibodies against Purkinje cells with a special focus on cerebrospinal fluid.Our results confirm a subacute disease with a severe cerebellar syndrome in 10 female patients due to anti-Yo antibodies associated mostly with gynecological malignancies. While standard cerebrospinal fluid parameters infrequently revealed pathological results, all patients presented oligoclonal bands indicating intrathecal IgG synthesis. Analyses of anti-Yo antibodies in cerebrospinal fluid by calculating the antibody specific index revealed intrathecal synthesis of anti-Yo antibodies in these patients. In analogy to anti-Yo syndrome, an intrathecal production of anti-Tr antibodies in one patient who presented with a paraneoplastic cerebellar syndrome was detected. In an additional patient, anti-Purkinje cell antibodies of unknown origin in the cerebrospinal fluid but not in serum were determined suggesting an isolated immune reaction within the central nervous system (CNS) and underlining the importance of investigating the cerebrospinal fluid.In conclusion, patients with a cerebellar syndrome display a distinct immune reaction within the cerebrospinal fluid including intrathecal synthesis of disease-specific antibodies. We emphasize the importance of a thorough immunological work up including investigations of both serum and cerebrospinal fluid.

Specific genetic alterations and tumor immune contexture characterize ovarian tumors with paraneoplastic degeneration and anti-Yo antibodies

Background Paraneoplastic cerebellar degeneration with anti-Yo antibodies (Yo-PCD) are rare autoimmune neurological diseases triggered by ovary or breast cancers. However, mechanisms allowing breakdown of immune tolerance to tumor antigens (Ags) are still unclear. Methods We collected 25 samples of Yo-PCD ovarian cancers to analyze the immunohistological (IHC) characteristics of these tumors and to perform genomic study by aCGH and NGS. We compared the results to 116 ovarian tumors without Yo-PCD. Results Yo-PCD ovarian tumors strikingly differ from those of non-PCD patients. Although 23 out of 25 are histologically classical high-grade serous carcinoma, they are characterized by increased immune cell infiltration, organization of T and B cells in tertiary lymphoid structures and presence of mature DC in contact with tumor cells. Analyzing the genes encoding for the Yo Ags, e.g. CDR2 and CDR2L, CGH revealed significant recurrent gains in CDR2L gene copy numbers in Yo-PCD tumors. CDR2L overexpression was detected by IHC in all Yo-PCD ovarian cancers. Moreover, NGS analysis revealed that 65% of the Yo-PCD ovarian cancer presented missense or non-sense mutations in at least 1 of the Yo Ags, while only 0.1% of un-selected ovarian tumors were mutated. No constitutional mutations were detected in Yo-PCD patients. Finally, all but 2 Yo-PCD ovarian cancers carried at least one genetic alteration on CDR2 or CDR2L genes (gains and/or mutations). Conclusions Altogether, these data show that genetic alteration of onconeural Ags, including gains and mutations, might be instrumental for induction of the remarkable anti-tumor immune response characterizing PCD.

Anti-Yo, chorea and hemiballismus: A case report

68-year-old female presented with involuntary movements. MRI was normal. Cerebrospinal fluid analysis was normal. whole body CT and biopsy confirmed diagnosis of metastatic adenocarnimoa. The autoimmune panel was positive for anti-Yo antibodies.

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.

A 54-Year-Old Woman with Progressive Ataxia

Paraneoplastic cerebellar degeneration (PCD) is a rare but devastating syndrome associated with autoantibodies targeting cerebellar antigens expressed by tumours outside of nervous system. PCD is most often associated with breast and gynecological cancers and can precede clinical manifestations of the cancer. Of the dozen autoantibodies associated with PCD, anti-Yo is the most commonly identified. In this report, we present a case of a woman with progressive cerebellar ataxia and anti-Yo antibody, who has microscopic high-grade serous carcinoma found with empiric total abdominal hysterectomy bilateral salpingo-oophorectomy (TAH-BSO). This case highlights the challenges in diagnosis, difficulty in identifying the occult malignancy, and the need for multidisciplinary collaboration between Internal Medicine, Neurology, Gynecology and Pathology. The literature relating to diagnosis, prognosis and treatment of PCD is also reviewed.

A Rare Case of Candida Brain Abscess Secondary to Metastatic Tongue Cancer on Initial Presentation

SESSION TITLE: Student/Resident Case Report Poster - Critical Care IV SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Fungal brain abscesses are rare causes for altered sensorium and they are often resistant to treatment, resulting in high morbidity and mortality. Brain abscesses are commonly caused due to fungal organisms, especially Candida species. CASE PRESENTATION: A 53 year old man with past medical history of diabetes presented to the emergency department after being found on the floor. The patient was alert and oriented only to place and person. Patient was diagnosed with diabetic ketoacidosis, acute kidney injury, acute pancreatitis for which he was appropriately treated. Computed tomography (CT) abdomen was consistent with left pyelonephritis and prostatic abscess. Initial urine, blood and stool cultures revealed Candida albicans. Intravenous micafungin and fluconazole were instituted based on culture reports. HIV test was negative. Magnetic resonance Imaging (MRI) of brain demonstrated ring enhancing lesions with vasogenic edema and abnormal restricted diffusion (Figure 1A & 1B). Lumbar puncture was noncontributory. Treatment was changed from micafungin to liposomal amphotericin B with fluconazole with which patient demonstrated both clinical and radiological improvement (Figure 2A &2B). Further evaluation showed an enhancing tongue mass with cervical lymphadenopathy. Biopsy proved the presence of Stage IVA squamous cell cancer of the tongue. Early neoplastic markers, Anti-Hu and Anti-Yo antibodies were negative. DISCUSSION: Candida cerebral abscess are mostly diagnosed at autopsy. An autopsy series demonstrated that up to 6% of patients with systemic candidiasis have evidence of undiagnosed CNS involvement as well. Risk factors include penetrating trauma, neurosurgical intervention, IV drug abuse, corticosteroid use, and malignancies. Candida brain abscesses can also be secondary to the infection of the adjacent structures or be secondary to hematogenous spread from endocarditis, intrabdominal or genitourinary tract infections as in our case. Risk factors present in our patient included diabetes mellitus and malignancy. Only 55% of blood cultures and 23% of lumbar puncture are positive for Candida1. CT and MRI are the preferred imaging modalities for diagnosing brain lesions and monitoring response to therapy. A definitive diagnosis can be achieved from stereotactic brain biopsy, although this is rarely reported. Infectious diseases society of America recommends liposomal Amphotericin B with flucytosine for several weeks to manage Candida brain abscess, switching to azole based therapy. CONCLUSIONS: This case demonstrates the need to consider fungal brain abscesses, as differentials for altered mental status and that with the aid of MRI and effective management, patients may improve neurologically as seen in this patient. Reference #1: Andrea M. Fennelly, Amy K. Slenker, Lara C. Murphy, Michael Moussouttas, Joseph A. Desimone. Candida cerebral abscesses: a case report and review of the literature. Med Mycol (2013) 51 (7): 779-784. DISCLOSURE: The following authors have nothing to disclose: Shyam Shankar, Sushilkumar Gupta, Ishan Malhotra, Mangalore Amith Shenoy, Hatem Desoky, Prarthna Chandar, William Pascal, Stephan Kamholz, Richard Periut, Chanaka Seneviratne, Yizhak Kupfer No Product/Research Disclosure Information

Maternal antineuronal antibodies and risk of childhood autism spectrum disorders: A case–control study

BackgroundThe etiology of autism is complex, and may involve the interaction between genetic and environmental factors. Recent studies suggested an association between maternal immune response and this disorder. MethodsForty-nine women with autistic children (cases) were studied in comparison with 73 women with normal children (controls). After interviewing for sociodemographic and clinical information, mothers' sera were tested for the presence of antineuronal antibodies. ResultsMothers of autistic children had significantly higher seropositivity for anti-Yo antibodies (34.7%) than control women (13.7%), with an (adjusted odds ratio of 2.60 (95% confidence interval, 1.03–6.61; p=0.044). Similarly, women with autistic children showed significantly higher seropositivity for antiamphiphysin than the control group (40.8% vs. 17.8%), with an adjusted odds ratio of 2.54 (95% confidence interval, 1.07–6.04; p=0.035). No significant association was found between autism spectrum disorders and maternal anti-Hu antibodies and anti-Ri antibodies, and the history of autoimmune diseases. ConclusionSome maternal antineuronal antibodies may contribute significantly to the risk of childhood autism.

Paraneoplastic opsoclonus-myoclonus-ataxia syndrome revealing dual malignancy

Dual malignancy has been rarely associated to paraneoplastic syndromes. We describe an unusual case of metachronous small cell lung carcinoma revealed by opsoclonus-myoclonus ataxia syndrome in a 69-year-old patient with known prostate adenocarcinoma, with positive anti-Hu and anti-Yo antibodies and good responsiveness to corticosteroids and chemotherapy.

Anti-Yo Antibodies in Children With ADHD: First Results About Serum Cytokines

Objective: We investigated whether ADHD children who are positive to Purkinje cell antibodies display pro-inflammatory activity associated with high cytokine serum levels. Method: Fifty-eight ADHD outpatients were compared with 36 healthy, age- and sex-matched children. Forty-five of the ADHD children were positive to anti-Yo antibodies, whereas 34 of the control children were negative. Interleukin 4 (IL-4), IL-6, IL-10, IL-17, tumor necrosis factor alpha (TNFα), and interferon gamma (IFNγ) cytokine serum levels were tested in ADHD children who were positive to anti-Yo antibodies and in the control children who were negative. Results: Anti-Yo antibodies were present to a greater extent in the ADHD group: 77.58% versus 22.42%. Significant differences emerged between the two groups in IL-6 and IL-10, with higher cytokine levels being detected in ADHD children than in controls. Conclusion: Immune processes in ADHD are likely to be associated with mediators of inflammation, such as cytokines. These results contribute to our understanding of action of neural antibodies and cytokines in ADHD.

Case Challenge Part 3 (Conclusion): A Woman with Ataxia and Abnormal Uterine Bleeding

Figure 3: Hematoxylin and eosin stain showed a poorly differentiated endometrioid adenocarcinoma of the ovary. Patient representative permission granted. The 46-year-old woman presenting with ataxia and bilateral adnexal masses (NEJM JW Neurol Mar 29 2016; [e-pub] and (NEJM JW Neurol Apr 5 2016; [e-pub]) had normal levels of carcinoembryonic antigen (CEA) and CA-19.9 but increased levels of serum CA-125 (2107 U/mL), and serum antibody testing was positive for anti-Yo antibodies. A bilateral pelvic mass resection was performed. Pathological examination revealed a poorly differentiated endometrioid adenocarcinoma of the ovary (see Figure 3). The patient then received consecutive adjuvant chemotherapy. On postoperative day 25, her slurred speech improved significantly but she continued having an ataxic gait. In this patient, subacute cerebellar ataxia accompanied by endometrioid adenocarcinoma and positive Anti-Yo antibodies are evidence of definite paraneoplastic cerebellar degeneration (PCD; J Neurol Neurosurg Psychiatry 2004; 75:1135). This rare immune-mediated condition is a nonmetastatic complication of cancer ( J Neuroimmunol 2004; …

Paraneoplastic cerebellar degeneration and dermatomyositis as first manifestations of underlying breast malignancy: a report of two cases and a brief review of the subject

Paraneoplastic syndromes are rare first manifestations of breast cancer. In this report, we present two cases of a 58-year-old woman and a 69-year-old woman presenting with acute symptoms of paraneoplastic cerebellar degeneration (PCD) and dermatomyositis, respectively, as the first sign of breast malignancy. The patient diagnosed with PCD presented initially with ataxia, was serum anti-Yo antibody negative, and subsequently investigated to have poorly differentiated intraductal breast carcinoma. Cerebellar symptoms regressed following breast cancer surgery and chemotherapy, highlighting the better neurological prognosis associated with anti-Yo antibody negative PCD. The rarity of these presentations highlights the necessity to include an occult malignancy in the differential diagnosis when attending to such patients.

Paraneoplastic cerebellar degeneration in a patient with ovarian cancer

ObjectiveHerein, we report a case of ovarian serous carcinoma with paraneoplastic cerebellar degeneration. Case reportA 44-year-old female presented to our hospital with dizziness, slurred speech, and ataxic gait. Brain magnetic resonance imaging was normal. A lumbar puncture revealed a normal cell count in the cerebrospinal fluid, but slightly elevated protein. Her serum cancer antigen -125 level was high (2126.4 U/mL), and abdominal computed tomography disclosed a pelvic mass measuring 11 cm in diameter. Exploratory laparotomy was then performed, and a frozen section of the tumor revealed serous carcinoma. ConclusionAccording to the surgical findings and pathological report, The International Federation of Gynecology and Obstetrics (FIGO) Stage IIIC, Grade 3, serous-type ovarian cancer was diagnosed. Due to the abovementioned symptoms and signs, we performed a serial test to document the presence of anti-Yo antibody in this patient.