anti-Yo Antibodies Research Articles

Francesc Graus: solving paraneoplastic puzzles

Francesc Graus: solving paraneoplastic puzzles

Anti-Yo Antibody Associated With Occult Fallopian Tube Carcinoma

This is the case report of a 61-year-old woman who presented with progressive diplopia and ataxia. Her cerebrospinal fluid revealed high titers of anti-Yo (PCA-1) antibody and a magnetic resonance imaging with contrast showed cerebellar degeneration. Extensive imaging workup was negative for malignancy and she was otherwise asymptomatic. Given the association between anti-Yo antibodies and gynecologic malignancies, she underwent a bilateral salpingo-oophorectomy and cancer staging. Extensive section of the fimbriated end of the fallopian tube revealed a stage 1, microscopic serous adenocarcinoma. After surgery, her anti-YO titers fell and plans were made for adjuvant chemotherapy. Her neurologic symptoms are not expected to substantially improve, illustrating the urgent need for early surgical investigation in cases of paraneoplastic syndrome, even in the absence of imaging evidence of a lesion.

Rhombencephalitis

The term rhombencephalitis refers to inflammatory diseases affecting the hindbrain (brainstem and cerebellum). Rhombencephalitis has a wide variety of etiologies, some of them potentially severe and life threatening without proper early treatment. In this retrospective observational study, we reviewed the records of consecutively hospitalized patients at University Hospital of Bellvitge (Barcelona, Spain) from January 1990 to December 2008. Rhombencephalitis was defined as a brainstem and/or cerebellar condition demonstrated clinically or by neuroimaging, with pleocytosis (>4 cells/mm) in cerebrospinal fluid. Ninety-seven patients (48 female; mean age, 37 yr; range, 14-79 yr) fulfilled these criteria. We reviewed their clinical, cerebrospinal fluid, and radiologic characteristics. The mean follow-up was 5 years (range, 0-20 yr). The etiologies of rhombencephalitis were as follows: unknown cause (n = 31), multiple sclerosis (n = 28), Behçet disease (n = 10), Listeria monocytogenes infection (n = 9), paraneoplastic syndrome (n = 6) (3 cases associated with anti-Yo antibodies and 3 with anti-Tr antibodies), Epstein-Barr virus (n = 4), tuberculosis (n = 2), pneumococcal infection (n = 2), systemic lupus erythematosus (n = 1), lymphoma (n = 1), Brucella species infection (n = 1), JC virus (n = 1), and relapsing polychondritis (n = 1). Certain clinical, cerebrospinal fluid, and radiologic characteristics that are commonly seen in some of these etiologies can guide us in the first approach to the etiologic diagnosis of rhombencephalitis.

Paraneoplastic cerebellar degeneration and anti-Yo antibodies

a Servicio de Neurologia, Hospital Universitario La Fe, Valencia, Spain b Laboratorio de Neurologia Experimental, Centro de Investigacion, Hospital Universitario La Fe; Valencia, Spain and Centro de Investigacion Biomedica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) c Servicio de Neurologia, Hospital Santa Maria del Rosell, Cartagena, Murcia, Spain d Servicio de Anatomia Patologica, Hospital Universitario La Fe, Valencia, Spain e E. Fages was working at the Servicio de Neurologia, Hospital Universitario la Fe, Valencia, Spain, when this paper was written

Neurally Mediated Syncope Associated with Small Cell Lung Cancer: A Case Report and Review

We encountered a case of limited-disease small cell lung cancer with episodic syncope. The frequency of the syncopal attacks increased with the increase in the tumor size, thus a relationship was suspected to exist between the SCLC and syncope. Syncope was evaluated by history taking, 24-hour ECG monitoring, and coronary angiography. As orthostatic hypotension and cardiac disease could be excluded, we finally diagnosed this case as neurally mediated syncope. Serum tests for anti-Hu and anti-Yo antibodies were negative. A temporary pacemaker was inserted for sick sinus syndrome. This patient showed good response to the chemotherapy. No further syncopal attacks were observed after the second course of chemotherapy. Here, in addition we review four cases of SCLC with episodic syncope. Interestingly, in all cases, the tumor was located in the left hilum in close vicinity of the afferent vagal nerve (C-fibers) and mechano-receptor. Therefore, we thought that the mechanism underlying the syncope was mechano-receptor hypersensitivity.

Long-term efficiency of intravenously administered immunoglobulin in anti-Yo syndrome with paraneoplastic cerebellar degeneration

Paraneoplastic cerebellar degeneration (PCD) is a rare heterogeneous group of disorders associated with cancer and anti-neuronal antibodies. Patients display symptoms reflecting cerebellar dysfunction including dysarthria, severe ataxia and abnormal oculomotor functions. Anti-Yo antibodies, also often called Purkinje cell antibodies type 1 (PCA-1), occur in patients with PCD having a history of tumors of the ovary, endometrium, fallopian tube or breast cancer [6, 11]. The treatment of PCD associated with antiYo antibodies is very limited and does usually not respond to immunosuppressive or tumor therapy. We report improvement and stabilization in a patient with an anti-Yo syndrome with PCD secondary to ovarian carcinoma through 10 years of treatment with intravenous immunoglobuline (IVIG). A 72-year-old female patient was diagnosed with an ovarian carcinoma with TNM-classification pT3, pN1, G3 at the age of 61 years. The patient subsequently underwent surgery followed by chemotherapy with Taxol 175 mg/m and carboplatin (according AUC 6) under hyperthermic conditions. The therapy was well tolerated without serious side effects. However, treatment resulted in a mild axonal motor and accentuated sensory polyneuropathy. At age 62 years, she presented with a progressive cerebellar syndrome with low saccadic eye movement and saccadic dysmetria, diplopia and horizontal spontaneous nystagmus as well as persistent ptosis bilaterally. She displayed marked limb and cerebellar ataxia with inability to walk unaided, an increased tendency to fall, and severe limb pain. Deep tendon reflexes were decreased in lower extremities; no pathological reflexes were seen. Additionally distal symmetric sensible polyneuropathy with hypaesthesia was present. Analysis of blood and cerebrospinal fluid (CSF) showed an elevated titer for Yo antibodies (serum 1:7,680, CSF 1:240) and a slight pleocytosis. MRI of the brain was normal. Under the diagnosis of anti-Yo syndrome with PCD, this patient was treated with IVIG initiated at age 62 years. Initially a total of 150 g of IVIG was applied every 3 weeks. The response was prompt with improvement of gait ataxia and pain. Walking was much easier and no further falls were reported. During IVIG therapy the antibody titers decreased to levels of about 1:480. Follow-up MRIs of the brain displayed normal findings. Treatment intervals could be prolonged and she received a total of 40 dosages of an average of 145 g of IVIG (90–200 g of IVIG) within the last 10 years with an average interval of 3 months (Fig. 1). Worsening of ataxia re-occurred after about 2 months after the last IVIG treatment. The IVIG product had to be changed three times after showing mild side effects such as fever and headache, which was also the reason for the dosage variation. IVIG is given with the comedication of i.v. prednisolone and i.v. dimetindenmaleat, an antihistamine. At the age of 68 years, a treatment escalation with rituximab (four times 375 mg/m body surface area) showed no further clinical benefits. During treatment with the co-medication 3,4-diaminopyridine, oculomotor dysfunctions like diplopia and nystagmus disappeared. Until today all cancer follow up examinations revealed no evidence of any new tumor or metastasis. Anti-Yo antibodies are, with a few exceptions, detected in patients with PCD secondary to breast, ovary and female genital tract carcinomas. Immunosuppressive or immunomodulatory therapies were considered due to the J. Schessl (&) M. Schuberth P. Reilich P. Schneiderat N. Strigl-Pill M. C. Walter B. Schlotter-Weigel B. Schoser Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians University of Munich, Ziemssenstr. 1 A, 80336 Munchen, Germany e-mail: joachim.schessl@med.uni-muenchen.de

Paraneoplastic cerebellar degeneration mimicking development of secondary progressive multiple sclerosis in a patient with relapsing–remitting multiple sclerosis

Paraneoplastic cerebellar degeneration (PCD) is a rare non-metastatic complication of cancer mediated by T lymphocytes and auto-antibodies directed against Purkinje cells of the cerebellum. We report a patient with relapsing–remitting multiple sclerosis who developed a progressive cerebellar syndrome with dysarthria, ataxic gait and vertigo mimicking development of secondary progressive multiple sclerosis but caused by anti-Yo antibody positive PCD associated with ovarian cancer, presenting an unusual diagnostic challenge.

Brainstem and spinal cord involvement in a paraneoplastic syndrome associated with anti-Yo antibody and breast cancer

Paraneoplastic neurological syndromes (PNS) are associated with breast cancer in\1% of cases [1]. Anti-Yo/PCA1 antibody is usually detected in female patients with breast or gynaecologic cancer and is most commonly associated with progressive cerebellar degeneration (PCD) [2–5]. Here we describe a case of a 60-year-old woman who, in May 2008, complained of progressive weakness of lower limbs followed, after 2 months, by dysesthesias in the four limbs, dysphagia, diplopia and sensory ataxia. Total body computed tomography (CT) scan, brain and spinal cord magnetic resonance imaging (MRI) were normal, electromyography (EMG) showed evidence of acute and chronic denervation in the four limb muscles, oligoclonal bands were present in the cerebrospinal fluid and serum anti-onconeural antibodies were negative. She was treated with steroids for several months with partial benefit but soon after drug discontinuation her symptoms worsened. At our first neurological examination in January 2010, the patient was unable to walk for severe sensory ataxia and showed lower limb weakness and spasticity, mild dysarthria, dysphagia, diplopia and dysesthesias in the four limbs. Sensory and motor evoked potentials were altered both at upper and lower limbs and EMG showed evidence of acute and chronic denervation in the muscles of upper and lower extremities. At that time, serum anti-Yo/PCA-1 antibody was positive. Total body CT scan and mammography showed evidence of a nodular opacity associated with two clusters of retroareolar microcalcifications in the left breast. A total body 2-deoxy-2-F-fluoro-D-glucose positron emission tomography (FDG PET)/CT imaging showed high metabolic activity in the right axillary lymph nodes but ultrasound scan (US) and MRI confirmed the left breast calcifications with no evidence of axillary lymph node pathological alterations bilaterally. The left mammary lesion was surgically removed in March 2010. Histopathological examination revealed the presence of foci of ductal carcinoma in situ of G2 grade. Radiotherapy and hormonal therapy were started in April 2010. Soon after the surgery, the neurological symptoms progressively improved. At the last neurological examination in July 2010, the ataxia was reduced and the patient was ambulatory without aid or rest for about 10 m, with only a mild proximal weakness of the legs and diplopia persisting. The EMG evaluation showed improvement mainly at the lower limbs with reduction of acute denervation signs. Despite the fact that, in our patient, the clinical picture was not evocative of a classical PNS, we suspected a paraneoplastic encephalomyelitis; we repeated tests for anti-onconeural antibodies and diagnostic investigations for cancer, and we found serum positivity for anti-Yo/ PCA-1 antibody associated with a ductal breast carcinoma in situ. Very few cases of anti-Yo/PCA-1 antibody associated PNS, different from PCD, have already been described including several cases of peripheral neuropathy [6, 7] and a case of motor neuron disease involving both the upper and the lower motor neurons [8]. All patients with PNS and anti-Yo/PCA-1 antibody associated breast cancer previously reported showed axillary lymph node metastases [9]. D. Plantone P. Caliandro R. Iorio G. Frisullo V. Nociti A. K. Patanella A. Marti P. A. Tonali A. P. Batocchi (&) Department of Neurosciences, Institute of Neurology, Catholic University, Largo Gemelli 8, 00168 Rome, Italy e-mail: annapaola.batocchi@rm.unicatt.it

Anti-Yo positive dorsal root ganglionopathy

A 62 year old Romanian lady presented with a 1 year history of pain in her hands and feet which radiated up her arms and legs. It progressed over the year to severe, sharp pain involving all four limbs, associated with a tingling sensation and numbness. Two months after onset of symptoms she required assistance to mobilise. On presentation she required bilateral assistance and used a wheelchair outside of her home. There was no sphincter disturbance. Past medical history included chronic hepatitis C infection (genotype 1b), ischaemic heart disease and hypertension. She was an ex-smoker. On examination, the gait was ataxic and she required the assistance of two people. She had a sensory ataxia which increased with her eyes closed. There was decreased soft touch and pinprick sensation to the elbows and knees bilaterally. Proprioception was decreased to the ankles. Vibration sensation was decreased to the elbows and knees. She was areflexic throughout. Plantars were downgoing bilaterally. Vitamin B12 and folate levels were normal. Serum electrophoresis was normal. Serum cryoglobulins were normal. HIV serology and syphilis serology were negative. ANA was positive at 1:80 with a nucleolar pattern. Cerebrospinal fluid examination was normal and oligoclonal bands were negative. On nerve conduction testing, the motor study was well preserved with uniformly absent sensory nerve action potentials consistent with a dorsal root ganglionopathy. CT thorax, abdomen and pelvis showed cirrhosis of the liver with splenomegaly but no evidence of any malignancy. She was treated with intravenous immunoglobulin therapy and started on pregabalin. There was minimal improvement in her condition. Western blot assay was negative for anti-HU, RI, MA1, MA2, anti-CV2/CRMP5 and anti-amphiphysin paraneoplastic antibody markers but positive for anti-Yo. GAD and MAG antibodies were also negative. This prompted a further search for a malignancy. Bilateral mammography was normal. PET scan showed intense uptake in bilateral ovarian masses and no other areas of abnormal uptake. Bilateral salpingo-oophorectomy was carried out and the histology showed stage III papillary serous carcinoma with omental metastases. She was commenced on carboplatin chemotherapy but only tolerated one cycle due to neutropenia, lymphopenia and thrombocytopenia. She had two further cycles of intravenous immunoglobulin therapy for worsening symptoms but with little improvement. We present this case as we believe it to be unusual that a paraneoplastic dorsal root ganglionopathy is associated with anti-Yo antibodies. Anti-Yo antibodies were first reported in 1983 by Greenlee et al. [1] when they reported antibodies to Purkinje cells in two patients with ovarian cancer and paraneoplastic cerebellar degeneration. Anti-Yo antibodies are usually associated with ovarian or breast cancer and typically present with a cerebellar syndrome [2]. Anti-Hu antibodies and CV2 antibodies are most commonly associated with dorsal root ganglionopathy or sensory neuronopathy as a paraneoplastic phenomenon [3]. Peripheral nerve manifestations associated with seropositivity for anti-Yo antibodies have been described previously by Tracy et al. They described six patients with peripheral neuropathies and positive anti-Yo antibodies from a cohort of 76 anti-Yo seropositive women who were P. McNamara (&) L. Costelloe J. Redmond Department of Neurology, St James’s Hospital, Dublin, Ireland e-mail: pmcnamara2004@hotmail.com

Purkinje Cell Death After Uptake of Anti-Yo Antibodies in Cerebellar Slice Cultures

Paraneoplastic cerebellar degeneration accompanying gynecological and breast cancers is characteristically accompanied by a serum and cerebrospinal fluid (CSF) antibody response, termed "anti-Yo," which reacts with cytoplasmic proteins of cerebellar Purkinje cells. Because these antibodies interact with cytoplasmic rather than cell surface membrane proteins, their role in causing Purkinje cell death has been questioned. To address this issue, we studied the interaction of anti-Yo antibodies with Purkinje cells in slice (organotypic) cultures of rat cerebellum. We incubated cultures with immunoglobulin G (IgG)-containing anti-Yo antibodies using titers of anti-Yo antibody equivalent to those found in CSF of affected patients. Cultures were then studied in real time and after fixation for potential uptake of antibody and induction of cell death. Anti-Yo antibodies delivered in serum, CSF, or purified IgG were taken up by viable Purkinje cells, accumulated intracellularly, and were associated with cell death. Normal IgG was also taken up by Purkinje cells but did not accumulate and did not affect cell viability. These findings indicate that autoantibodies directed against intracellular Purkinje cell proteins can be taken up to cause cell death and suggest that anti-Yo antibody may be directly involved in the pathogenesis of paraneoplastic cerebellar degeneration.

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

Cerebrospinal fluid study in paraneoplastic syndromes

Objective:Paraneoplastic neurological syndromes (PNS) probably result from an immune reaction against antigens shared by the nervous system and tumour cells. To characterise CSF alterations in these syndromes, we studied a...

Effective immunosuppressant therapy with cyclophosphamide and corticosteroids in paraneoplastic cerebellar degeneration

Paraneoplastic cerebellar degeneration (PCD) is a rare immune mediated phenomenon often associated with cancer of the ovarian. Hitherto, tumor dissection is the mainstay in therapy while immunomodulatory treatment regimes often fail. Here we report on an 86 year old female patient who developed a severe pancerebellar syndrome. Clinical course, onconeural (anti-Yo) antibodies and detection of ovarian cancer suggest the assumption of PCD as the most probable diagnosis. We initiated a high-dose course of corticosteroids followed by a single dose of cyclophosphamide (600 mg/day). Surprisingly patient's condition improved and stabilized within days subsequent to cyclophosphamide application. This case demonstrates the benefit of immunosuppressive therapy in an anti-Yo positive patient with severe PCD secondary to an ovarian cancer.

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.

A Case Report of Plasmapheresis Treatment in a Patient With Paraneoplastic Cerebellar Degeneration and High Anti‐Yo Antibody Titers

A patient with paraneoplastic cerebellar degeneration due to anti-Purkinje cell antibodies (anti-Yo) arising from ovarian carcinoma with metastases was treated with three plasmapheresis (PP) series (a total of 22 PP treatments) over one year and was monitored by repeated otoneurological testing, balance tests and clinical investigations. Blood samples for antibody titers were checked on several occasions. Initially there was a weak clinical response and significantly improved test results regarding the caloric response, as well as a possible effect on visual suppression of the vestibulo-ocular reflex after caloric ear irrigation. After the first series of PP treatment, new metastases were found. A half year later there was a progressive course with increasing general symptoms. Serology tests showed continuously high titers of anti-Yo antibody, although somewhat lower after PP. We thus report a minor and short-lived effect of PP, possibly inhibited by the natural course of metastatic disease.

Paraneoplastic cerebellar degeneration in ovarian carcinoma: case report with review of immune modulation

Paraneoplastic cerebellar degeneration (PCD) is a rare nonmetastatic complication of a carcinoma. It is typically mediated by antibodies generated against tumor antigens. These antigens are the same proteins as expressed on Purkinje cells within the cerebellum; immune activation in the central nervous system (CNS) results in the syndrome. A 56-year-old woman with stage IIIC serous ovarian carcinoma diagnosed 3 years prior developed progressive limb ataxia. Serum anti-Yo antibodies were positive, confirming the diagnosis of PCD. Treatment with plasmaphoresis, intravenous immune globulin, and immune modulation with corticosteroids and tacrolimus was unsuccessful. Although the syndrome can be debilitating and treatment options are limited, it may also be an example of a successful host immune response in certain cases.

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

Asymptomatic persistence of anti‐Yo antibodies for 5 years without relapse of malignancy

Neurological paraneoplastic syndromes (NPS) are rare disorders in association with malignancy and the presence of various antineuronal antibodies. The persistence of antineuronal antibodies for years after the eradication of the tumor without clinical manifestations of a NPS has not been reported. In a 64-year-old woman with a history of gynecologic malignancy, treated by surgery and chemotherapy with docetaxel and carboplatin, ptosis, hypertelorism, dysarthria, short stature, upper and lower limb weakness, exaggerated tendon reflexes and recurrent creatine-kinase elevation were found. Nerve conduction studies disclosed polyneuropathy and muscle biopsy nonspecific myopathic features. Though anti-Yo antibodies were repeatedly positive, the clinical findings and polyneuropathy were rather attributed to a suspected metabolic myopathy or chemotherapy than a NPS. Anti-Yo antibodies remained positive at 5 further determinations. During the 5 years of follow up there was improvement of polyneuropathy and no relapse of the malignancy, as assessed clinically, by tumor markers, computed tomography scans and 18-fluorodeoxyglucose positron emission tomography. Anti-Yo antibodies may occur without the typical clinical manifestations of a NPS and may persist for years without the development of a NPS or relapse of the tumor.

A rare gynecological case of paraneoplastic cerebellar degeneration discovered by FDG-PET

Background. PET/CT may be particularly useful to detect the primary cancer in paraneoplastic cerebellar degeneration (PCD) with anti-Yo which is most commonly associated with breast, ovarian and other gynecological cancers. Case. A 60-year-old woman developed a PCD associated with anti-Yo antibodies in serum and cerebrospinal fluid. Conventional imaging was negative. FDG-PET showed an abnormal hot spot in the right ovarian area associated with lombo aortic lymph nodes. The diagnosis was confirmed by surgery as an ovarian adenocarcinoma. Conclusion. In this case report, FDG-PET played a crucial role in detecting the unknown primary tumor in a patient with PCD.

Detection of Autoantibodies to the BTB‐kelch Protein KLHL7 in Cancer Sera

The aim of the study was to search for novel targets of autoantibodies in patients with paraneoplastic neurological syndromes (PNS). PNS are mediated by immune reactions against autoantigen(s) shared by the cancer cells and the nervous system. By serological screening of a rat cerebellum cDNA expression library using anti-Hu-positive sera from three patients with paraneoplastic encephalomyelitis (PEM), we identified an open reading frame encoding an isoform of the BTB-kelch protein KLHL7. Immunohistochemical studies demonstrated that the KLHL7 protein is expressed in the nuclei of neurones, but not in other tissues including various cancers. However, the KLHL7 protein was detected in the nuclei of cancer cell lines. Antibodies to KLHL7 were detected by an immunoprecipitation assay in sera from 12 of 254 (4.7%) patients with various cancers and 2 of 170 blood donors (1.2%). None of 50 sera from patients with multiple sclerosis were positive for KLHL7 antibodies. Sixteen patients with classical PNS and anti-Hu or anti-Yo antibodies were also negative for KLHL7 antibodies. Seven cancer patients with KLHL7 antibodies had various signs of neurological disease that could be related to cancer, whereas the remaining five seropositive cancer patients had no clinical signs of possible PNS. The present results indicate that KLHL7 antibodies are associated with various cancers, and in some patients also with neurological disease. Whether KLHL7 antibodies can be used as paraneoplastic markers for PNS remains to be determined.