anti-Hu Antibodies Research Articles

A unique case of pronounced neurologic deficit from paraneoplastic syndrome that precedes appearance of mediastinal germinoma by two years

Paraneoplastic neurologic disorder may be the initial manifestation of a tumor, with the diagnosis of malignancy commonlyfound within six months of the onset of neurologic symptoms. This diagnosis is usually made on clinical grounds, as antineuronalantibodies are infrequently positive, though anti-Hu antibodies have been associated commonly with lung cancer. Typically,neurologic manifestations of germinomas include limbic and brainstem encephalitis in association with anti-Ma2 antibodies.To our knowledge, germinomas have not been associated with paraneoplastic cerebellar degeneration with anti-Hu antibodypositivity. Here we report a case where neurologic deficits and anti-Hu positivity indicative of a paraneoplastic syndrome precedesthe development of a mediastinal germinoma by two years.

Fatal paraneoplasic encephalo-myelo-neuropathy associated with anti-Hu antibodies: a case report

Fatal paraneoplasic encephalo-myelo-neuropathy associated with anti-Hu antibodies: a case report

Limbic Encephalitis as a Manifestation of Small Cell Lung Cancer

SESSION TITLE: Lung Cancer Student/Resident Case Report Posters SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 27, 2015 at 01:30 PM - 02:30 PM INTRODUCTION: Small cell lung cancer commonly presents with widespread metastasis, involving mediastinal and hilar lymph nodes. As this is a neuroendocrine tumor, paraneoplastic syndromes are common, and can precede the malignancy diagnosis. CASE PRESENTATION: Ms. S is a 73-year-old female with a 7 pack-year history of cigarette smoking who presented to our hospital with 2 weeks of altered mental status. Two weeks prior she saw a neurologist and on the same day experienced her first witnessed tonic-clonic seizure. She was started on levatiracetam for prophylaxis. Several days prior to admission she was noted to be persistently confused without return to baseline. On the day of admission Ms. S experienced a second seizure at home and was brought to our hospital. Family members denied recent travel, sick contacts or other associated symptoms. On neurological examination she was oriented to self only and unable to follow commands. The rest of her physical and neurological examination was unremarkable. MRI brain revealed symmetric non-hemorrhagic, non-enhancing abnormalities in the hippocampus consistent with encephalitis. Lumbar puncture showed 27 WBCs with 97% lymphocytes and normal glucose and protein. Intravenous acyclovir was started for presumed HSV encephalitis without improvement in symptoms. Serology for HSV, syphilis, hepatitis, West Nile Virus, and Cryptococcus were all negative. Repeat MRI 15 days later showed worsening encephalitis. At that time CT of the chest, abdomen and pelvis showed an enlarged para-tracheal lymph node measuring 2.1 cm x 1.8 cm without any abnormalities of the lung parenchyma. Biopsy of the lymph node showed small cell cancer. Ms. S was treated with plasmapheresis and IV prednisone with minimal improvement. She was then given one dose each of rituximab and cyclophosphamide followed by significant improvement in her neurologic symptoms. DISCUSSION: Small cell lung cancer presented in this patient as only a solitary lymph node and paraneoplastic encelphalitis, without any additional lung findings. Serologic testing for anti-Hu antibodies is positive in approximately 50% these patients. CONCLUSIONS: Limbic encephalitis has many etiologies including infectious, autoimmune and paraneoplastic. Once infectious etiologies have been ruled out, paraneoplastic encephalitis should be considered a possibility. Initial workup includes CT scan of the chest to detect small cell lung cancer, as it is the most common cancer associated with paraneoplastic limbic encephalitis. Even if no clear lung pathology exists on imaging, abnormal lymph nodes should be biopsied for possible diagnosis. Reference #1: Govindan, R et al. 2006, Journal of Clinical Oncology, vol. 24, no. 28, pp. 4539-4544. Reference #2: Alamowitch, S, et al. 1997, “Limbic encephalitis and small cell lung cancer. Clinical and immunological features”, Brain, vol. 120, no. 6, pp. 923-928. DISCLOSURE: The following authors have nothing to disclose: Katie Jeans, Eva Clark, Jayasimha Murthy No Product/Research Disclosure Information

Orthostatic hypotension and delirium; an unusual presentation of the Anti-Hu antibody related paraneoplastic syndrome

Orthostatic hypotension and delirium; an unusual presentation of the Anti-Hu antibody related paraneoplastic syndrome

Intestinal pseudo-obstruction: An important diagnostic challenge

We present the case of a 72-year-old patient admitted on various occasions with symptoms of intestinal pseudo-obstruction. Extensive diagnostic tests eventually found that the patient had small-cell lung cancer associated with high anti-HU antibody titres, which pointed to a probable paraneoplastic intestinal obstruction syndrome associated with small-cell lung cancer. A paraneoplastic syndrome causing abnormal changes in gastrointestinal motility can be the first signs of small cell lung cancer. These syndromes improve with treatment of the underlying disease, as seen in our patient, who stopped having episodes of intestinal pseudo-obstruction after administration of chemotherapy.

Pediatric anti-Hu-associated encephalitis with clinical features of Rasmussen encephalitis.

Anti-Hu antibodies (anti-neuronal nuclear antibodies, type 1) are associated with paraneoplastic encephalomyelitis in adults, especially those with small cell lung cancer. Anti-Hu antibodies are extremely rare in children, but they have been observed in neuroblastoma with or without opsoclonus-myoclonus syndrome or in limbic encephalitis without associated malignancy.1 However, anti-Hu antibodies are not typically associated with clinical features of Rasmussen encephalitis (RE). Acknowledgment: The authors thank Sean J. Pittock, MD, for his assistance in the interpretation of serum and CSF anti-Hu antibody titers and for explaining the methodologic processes involved in the Mayo Clinic Paraneoplastic Antibody Panel.

Paraneoplastic subacute lower motor neuron syndrome associated with solid cancer

We retrospectively analyzed three patients with pure motor neuronopathy followed for more than four years in our center. The patients presented a rapidly progressive lower motor neuron syndrome (LMNS) over the course of a few weeks leading to a severe functional impairment. The neurological symptoms preceded the diagnosis of a breast adenocarcinoma and a thymoma in the first two patients, one of them with anti-CV2/CRMP5 antibodies. Cancer was not detected in the third patient who had circulating anti-Hu antibodies. A final diagnosis of paraneoplastic syndrome was made after investigations for alternative causes of lower motor neuron syndrome. Early diagnosis, combined treatment of the underlying cancer, and immunomodulatory treatment led to neurological improvement of the disease in two out of the three cases in which the cancer was diagnosed. Cases of subacute LMNS with rapid progression may occur as an expression of a paraneoplastic neurological syndrome. Identification of these syndromes is important, as the treatment of underlying malignancy along with immunomodulatory treatment may result in a favorable long-term outcome of these potentially fatal diseases.

Paraneoplastic Limbic Encephalitis and Small-Cell Lung Carcinoma

Journal of Thoracic Oncology ® • Volume 10, Number 5, May 2015 A 64-year-female smoker presented with a prolonged history of altered behavior, personality changes, and seizures. Anti-HU and anti-RI antibodies were positive. Magnetic resonance imaging demonstrated hyperintensity in the right hippocampal region (Fig. 1A) and corresponding increased radiotracer activity on positron emission tomography–computed tomography (PET-CT) (Fig. 1B, C). This initial PET-CT was negative for malignancy. A follow-up PET-CT 6 months later showed increased uptake in a right hilar node (Fig. 2). This node was sampled with endobronchial ultrasound and fine needle aspirate confirmed small cell carcinoma. Paraneoplastic limbic encephalitis is characterized by clinical presentation, presence of antineuronal antibodies, and imaging findings confirming involvement of the limbic system. Clinical symptoms and imaging abnormalities can predate the detection of malignancy by months to years. Control and treatment of the primary tumor with chemotherapy or other antineoplastic treatments may result in a neurologic improvement. Immunosuppression with steroids, intravenous immune globulin, plasma exchange, and other immunotherapies may also be of value. Symptomatic treatment should include seizure control with antiepileptic medications and medications to improve autonomic symptoms.

“Non-classical” paraneoplastic neurological syndromes associated with well-characterized antineuronal antibodies as compared to “classical” syndromes — More frequent than expected

ObjectivesParaneoplastic neurological syndromes (PNSs) are rare disorders in association with cancer and sub-divided into “classical” and “non-classical” syndromes according to a 2004 consensus paper proposed by a panel of PNS experts. “Classical” PNSs are regarded to account for the vast majority of cases. However, systematic reports on clinical PNS manifestations are rare. Therefore, we analyzed the spectrum of PNS in our clinic. MethodsWe retrospectively investigated medical records from consecutive patients diagnosed with definite PNS and serological evidence of well-characterized onconeural antibodies (anti-Hu, Yo, Ri, CV2/CRMP5, Ma1, Ma2, and amphiphysin) analyzed between 1991 and 2014 in our clinic. ResultsOf the 50 patients identified with onconeural antibody-positive PNS, 28 patients (56.0%) had “classical” PNS, and 22 (44.0%) “non-classical” PNS. Subacute cerebellar degeneration was the most frequent “classical” syndrome, brainstem encephalitis and subacute sensorimotor neuronopathy the most frequent “non-classical” syndromes. Anti-Hu antibodies were most frequent in both groups. 86.1% of patients developed neurological symptoms before the cancer was known. No differences between “classical” and “non-classical” syndromes were detected with respect to age, tumor entities and median time to diagnosis. However, whereas most patients with “classical” syndromes were females, there was no gender predominance in patients with “non-classical” PNS and the latter had significantly more frequent peripheral neurological syndromes. ConclusionsThe so-called “non-classical” PNSs in association with well-characterized onconeural antibodies were more common in our patient population than expected. Therefore, in neurological disorders of unclear etiology with a subacute onset and atypical presentation further diagnostic work-up including investigation of onconeural antibodies is necessary.

A Case of Esophageal “Double Jeopardy”

Question: A 66-year-old male outpatient was evaluated for progressive dysphagia to liquids and solids, which had slowly developed over 6 years. He also described a background of longstanding heartburn treated with proton pump inhibitor therapy for more than 10 years. In the last few years, his heartburn had largely resolved. His past medical history was significant for rheumatoid arthritis and hypercholesterolemia. Physical examination revealed no palpable lymphadenopathy, no cranial nerve deficits, and no significant cardiorespiratory or abdominal findings. A barium esophagram showed a 12-cm column of barium and no peristalsis (Figure A). High-resolution manometry revealed an absence of peristalsis, elevated basal lower esophageal sphincter pressure without relaxation, and panesophageal pressurization consistent with type II achalasia (Figure B). Endoscopy showed a fluid-filled esophagus with resistance to passage of the scope through the gastroesophageal junction. Endoscopic images are provided in Figure C. What is the diagnosis? Look on page 712 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. The endoscopic images (Figure C) reveal a dilated esophagus with mucosal changes consistent with long-segment Barrett’s esophagus. Biopsies confirmed the presence of specialized intestinal metaplasia but in several biopsies high grade dysplasia and intramucosal cancer was detected (Figure D). A paraneoplastic panel, including ANNA-1/anti-Hu and calcium channel antibodies was negative. Positron emission tomography showed a tiny focus of activity in the distal esophagus. Endoscopic ultrasonography combined with endoscopic mucosal resection demonstrated a T1b stage esophageal adenocarcinoma. Achalasia and Barrett’s esophagus co-occurring in the same patient is a rare clinical scenario. The added complexity to this case was the finding of an early esophageal cancer. Theoretically, achalasia should protect against reflux, but this patient had decades of reflux before developing achalasia symptoms. In our patient, the intramucosal cancer was not the cause for dysphagia and esophageal dilation, but an incidental finding. Hence, this is not a case of pseudoachalasia owing to an obstructing adenocarcinoma or to a paraneoplastic phenomenon. Barrett’s esophagus and achalasia usually coexist several years after achalasia intervention, such as myotomy or pneumatic balloon dilation, presumably owing to the development of gastroesophageal reflux disease. In 2 studies where follow-up endoscopy was performed at intervals ranging from 5 to 9 years after myotomy, Barrett’s esophagus had developed in 7% and 8.4% of patients, respectively.1Leeuwenburgh I. Scholten P. Caljé T.J. et al.Barrett's esophagus and esophageal adenocarcinoma are common after treatment for achalasia.Dig Dis Sci. 2013; 58: 244-252Crossref PubMed Scopus (34) Google Scholar, 2Gossage J. Devitt P.G. Watson D.I. et al.Surveillance endoscopy at five or more years after cardiomyotomy for achalasia.Ann Surg. 2014; 259: 464-468Crossref PubMed Scopus (22) Google Scholar Only a handful of cases exist where Barrett’s esophagus has been noted to coexisting with achalasia before achalasia therapy, and to our knowledge this is the first reported case where intramucosal cancer was present at the index endoscopy. Furthermore, there may be an increased risk of adenocarcinoma among patients who develop Barrett’s esophagus after achalasia therapy, ranging from 0.2 to 20.1Leeuwenburgh I. Scholten P. Caljé T.J. et al.Barrett's esophagus and esophageal adenocarcinoma are common after treatment for achalasia.Dig Dis Sci. 2013; 58: 244-252Crossref PubMed Scopus (34) Google Scholar Whether the same cancer risk applies to patients with coexisting Barrett’s at the time of achalasia diagnosis is unknown. A population-based study from Sweden also suggested that achalasia is a risk factor not only for squamous cell cancer of the esophagus, but also adenocarcinoma.3Zendehdel K. Nyrén O. Edberg A. et al.Risk of esophageal adenocarcinoma in achalasia patients, a retrospective cohort study in Sweden.Am J Gastroenterol. 2011; 106: 57-61Crossref PubMed Scopus (84) Google Scholar Our case highlights that mucosal changes in an achalasia patient should not simply be attributed to esophageal stasis, and biopsies are mandatory. Our patient elected for endoscopic therapy of his early esophageal adenocarcinoma. This was achieved by endoscopic mucosal resection, after which no residual high-grade dysplasia or esophageal adenocarcinoma was identified. Attempts at achieving complete remission from Barrett’s esophagus were attempted by radiofrequency ablation, but this was complicated by considerable delayed bleeding, which responded to endoscopic therapy. At 7 months after successful endoscopic mucosal resection, the decision was made to treat his achalasia with a Heller myotomy. This procedure was successful, despite the surgeon noting extensive scarring as a result of the prior endoscopic therapies. We plan to continue surveillance of his residual nondysplastic Barrett’s esophagus at regular intervals indefinitely.

Paraneoplastic Encephalopathy Presenting with Rapidly Progressive Dementia and Catatonia

Introduction: Paraneoplastic encephalopathy can present with neurological and psychiatric symptoms, and it is important to be aware of possible underlying medical etiologies of seemingly psychiatric presentations. In this case, cancer-associated limbic encephalitis presented with classical signs of catatonia, progressive cognitive decline and psychotic depression. Methods: A 68-year-old Caucasian female with past medical history of COPD, ongoing heavy tobacco use, and depression presented with rapidly worsening cognitive function over a nine months. Her cognitive symptoms were accompanied by psychotic features and delusions of ruin that her body and hair were burnt. Her medications on presentation included sertraline, trazodone, quetiapine and clonazepam. Physical examination was remarkable for classical signs of catatonia including catalepsy, gegenhalten, staring, perseveration, echolalia, echopraxia, hypophonia, and automatic obedience. MOCA scores were 19/30. Medical work-up undertaken for rapidly progressive dementia included a paraneoplastic antibody panel due to concerns of paraneoplastic limbic encephalitis. Anti-Hu antibodies were positive and further investigation revealed Stage IIIA small cell lung cancer. The patient was started on venlafaxine and mirtazapine for depression, olanzapine for psychosis and for paraneoplastic syndrome she was referred for treatment of underlying cancer and received a short course of steroids, which improved her cognitive function remarkably. Lorazepam helped improve catatonic symptoms. Results: The early detection of small cell lung cancer in limited stage (IIIA) resulted from the paraneoplastic work up prior to onset of physical symptoms and increased the possibility of curative treatment with radiation therapy and chemotherapy. Conclusions: The early detection of small cell lung cancer in limited stage (IIIA) resulted from the paraneoplastic work up prior to onset of physical symptoms and increased the possibility of curative treatment with radiation therapy and chemotherapy. Paraneoplastic syndromes should be considered on the differential for rapid cognitive decline, psychosis and personality changes especially when there is increased suspicion for malignancy.

66. Autonomic-sensory neuropathy onset in a patient with acute brainstem impairment – A case report

Here we report on a 64-year-old Caucasian man admitted to the Neurology department due to a history of severe hypoacusia, nausea, stipsis, cerebellar ataxia and progressing consciousness impairment, which raised up the clinical suspicion of acute cerebellitis and suggested the introduction of oral corticosteroids. At day 7, a mild improvement of cerebellar symptoms was followed by the onset of orthostatic hypotension, four limb sensory impairment and areflexia. The spinal tap displayed a mild protein increase (78 mg/dl) and high-titer of anti-Hu (ANNA-1) antibodies in CSF. The same antibodies were also found after blood testing. Nerve conduction velocities (NCV) of the four limbs showed a picture of severe peripheral neuropathy with predominant sensory and axonal features, absence of sympathetic skin response. No sensory evoked potentials were detectable either at upper and lower limbs, while cranial district reflexes and NCV were not affected. Autonomic tests confirmed severe orthostatic hypotension with mild parasympathetic involvement. A PET study highlighted a hypercaptation in the right paratracheal region, which a bronchoscopy with transbronchial biopsy identified as a possible lung cancer. Therefore, the patient was diagnosed with dysimmune rhombencephalitis and polyneuropathy in a likely paraneoplastic syndrome.

Chronic intestinal pseudo-obstruction as an expression of inflammatory enteric neuropathy

Chronic intestinal pseudo-obstruction (CIPO) is characterised by inadequate digestive tract motility and can lead to severely disordered motility. CIPO manifests as recurrent episodes of intestinal sub-occlusion without an anatomical obstruction. We present the case of a 41-year-old female, with severe chronic constipation and several episodes of intestinal sub-occlusion. Investigation revealed colonic inertia and marked distension of the small bowel and colon with no evidence of stenosis or obstructive lesions, compatible with CIPO. After several treatments were tried (domperidone, erythromycin, cisapride, octreotide, total enteral nutrition), with partial or no response, further work-up was done trying to identify an etiology. Gastrointestinal manometry showed neuropathic type abnormalities, transmural biopsy of the jejunum revealed degenerative enteric neuropathy and anti-HU antineuronal antibody screen was positive, suggesting an autoimmune type neuropathy with diffuse involvement of the digestive tract. Corticosteroids showed partial improvement of short duration and azathioprine was also tried but discontinued due to intolerance. Marked dietary intolerance and malnutrition lead to total parenteral nutrition (TPN) at home since October 2011. Since then, symptoms and nutritional status improved, with rare episodes of pseudo-obstruction, not requiring hospitalisation.

Neuronal uptake of anti-Hu antibody, but not anti-Ri antibody, leads to cell death in brain slice cultures.

BackgroundAnti-Hu and anti-Ri antibodies are paraneoplastic immunoglobulin (Ig)G autoantibodies which recognize cytoplasmic and nuclear antigens present in all neurons. Although both antibodies produce similar immunohistological labeling, they recognize different neuronal proteins. Both antibodies are associated with syndromes of central nervous system dysfunction. However, the neurological deficits associated with anti-Hu antibody are associated with neuronal death and are usually irreversible, whereas neurological deficits in patients with anti-Ri antibody may diminish following tumor removal or immunosuppression.MethodsTo study the effect of anti-Hu and anti-Ri antibodies on neurons, we incubated rat hippocampal and cerebellar slice cultures with anti-Hu or anti-Ri sera from multiple patients. Cultures were evaluated in real time for neuronal antibody uptake and during prolonged incubation for neuronal death. To test the specificity of anti-Hu antibody cytotoxic effect, anti-Hu serum IgG was incubated with rat brain slice cultures prior to and after adsorption with its target Hu antigen, HuD.ResultsWe demonstrated that: 1) both anti-Hu and anti-Ri antibodies were rapidly taken up by neurons throughout both cerebellum and hippocampus; 2) antibody uptake occurred in living neurons and was not an artifact of antibody diffusion into dead cells; 3) intracellular binding of anti-Hu antibody produced neuronal cell death, whereas uptake of anti-Ri antibody did not affect cell viability during the period of study; and 4) adsorption of anti-Hu antisera against HuD greatly reduced intraneuronal IgG accumulation and abolished cytotoxicity, confirming specificity of antibody-mediated neuronal death.ConclusionsBoth anti-Hu and anti-Ri antibodies were readily taken up by viable neurons in slice cultures, but the two antibodies differed markedly in terms of their effects on neuronal viability. The ability of anti-Hu antibodies to cause neuronal death could account for the irreversible nature of paraneoplastic neurological deficits in patients with this antibody response. Our results raise questions as to whether anti-Ri antibody might initially induce reversible neuronal dysfunction, rather than causing cell death. The ability of IgG antibodies to access and react with intracellular neuronal proteins could have implications for other autoimmune diseases involving the central nervous system.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-014-0160-0) contains supplementary material, which is available to authorized users.

ONDINE'S CURSE

Ondine was cursed and had to remember to breath. Acquired central hypoventilation is rare but potentially treatable.A 60 year old woman was admitted to intensive care with increasing drowsiness and...

Peripheral neuropathies associated with antibodies directed to intracellular neural antigens

Antibodies directed to intracellular neural antigens have been mainly described in paraneoplastic peripheral neuropathies and mostly includes anti-Hu and anti-CV2/CRMP5 antibodies. These antibodies occur with different patterns of neuropathy. With anti-Hu antibody, the most frequent manifestation is sensory neuronopathy with frequent autonomic involvement. With anti-CV2/CRMP5 the neuropathy is more frequently sensory and motor with an axonal or mixed demyelinating and axonal electrophysiological pattern. The clinical pattern of these neuropathies is in keeping with the cellular distribution of HuD and CRMP5 in the peripheral nervous system. Although present in high titer, these antibodies are probably not directly responsible for the neuropathy. Pathological and experimental studies indicate that cytotoxic T-cells are probably the main effectors of the immune response. These disorders contrast with those in which antibodies recognize a cell surface antigen and are probably responsible for the disease. The neuronal cell death and axonal degeneration which result from T-cell mediated immunity explains why treating these disorders remains challenging.

A prospective open-label study of sirolimus for the treatment of anti-Hu associated paraneoplastic neurological syndromes.

Several lines of evidence suggest a T cell-mediated immune response in paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS). In order to investigate whether suppression of T cell-mediated immune responses in Hu-PNS patients improved their neurological outcome, we performed a prospective open-label, single-arm study on sirolimus. Seventeen progressive Hu-PNS patients were treated with sirolimus with an intended treatment duration of 8 weeks. Primary outcome measures were (i) functional improvement, defined as a decrease of one or more points on the modified Rankin Scale (mRS), and (ii) improvement of neurological impairment, defined as an increase of one or more points on the Edinburgh Functional Impairment Tests (EFIT). One patient showed improvement on both clinical scales (mRS and EFIT). This patient presented with limbic encephalitis and improved dramatically from an mRS score of 3 to mRS 1. Another patient, with subacute sensory neuronopathy, remained stable at mRS 2 and improved one point on the EFIT scale. The other patients showed no improvement on the primary outcome measures. Median survival was 21 months. We conclude that treatment of Hu-PNS patients with sirolimus may improve or stabilize their functional disabilities and neurological impairments. However, the effects of this T cell-targeted therapy were not better than reported in trials on other immunotherapies for Hu-PNS. Trial Registration https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-000793-20/NL.

Diagnosis problems of paraneoplastic cerebellar degeneration

Paraneoplastic cerebellar degeneration (PCD) is a rare form of the paraneoplastic neurological syndrome (PNS). PCD is an autoimmune disease of the central nervous system (CNS) affecting the Purkinje cells and possibly other cells of the cerebellum. PCD is characterized by a rapid onset resulting in disability for a few days or weeks; a slow progredient increase in cerebellar symptomatology is observed less often. PCD develops in 1–3% of cancer patients; its fraction accounts for 25% of all forms of PNS. The mean incidence rate of PCD is about 2 cases per 1,000 cancer patients. PCD develops in patients with cancer of the ovary, uterus and fallopian tubes, with small cell lung cancer and Hodgkin's lymphoma. The incidence rate among females is 3 times higher than that among males. Females aged 50–65 years are most likely to suffer from PCD. PCDs are divided into four main subgroups that differ in terms of prognosis and range of associated antineuronal antibodies. In the last decade, different classes of anti-onconeuronal antibodies associated with PCD have been described; 9 of them have been best studied. Anti-Yo and anti-Hu antibodies are most frequently detected upon PCD. PCD can be also diagnosed without anti-onconeuronal antibodies associated with it or their titer in the blood can be low. Differential diagnosis of PCD is complex and is conducted for a wide range of CNS diseases. No single approach to treating PCD currently exists. Surgical removal of the tumor, the source of production of anti-onconeuronal antigens, followed by radiotherapy and/or chemotherapy, does not solve the problem completely, but may reduce severity of the clinical manifestations of PCD or stabilize the pathological process. This explains the need for rapid and profound search for a tumor in patients suspected with PCD. The authors described a clinical case of an acute debut of PCD in 47-year-old female, 6 months after which, the patient was diagnosed with breast cancer. The problems of PCD diagnosis by neurologists are discussed. The importance of the interdisciplinary approach to diagnosis and follow-up monitoring of patients with this nosology is noted.

Multiple Cranial Neuropathy in Paraneoplastic Anti-Hu Antibody Syndrome (P4.029)

Multiple Cranial Neuropathy in Paraneoplastic Anti-Hu Antibody Syndrome (P4.029)

NMDA-receptor antibody and anti-Hu antibody positive paraneoplastic syndrome associated with a primary mediastinal seminoma

Paraneoplastic neurological syndromes (PNS) are mostly immune-mediated, tumor-associated disorders that can develop years before detection of any malignancy. Their prevalence varies among different tumor types. Diagnostic criteria for PNS include the presence of a classical or nonclassical clinical syndrome in association with antineuronal antibodies and the presence of any malignancy [1]. We report the case of a 32-year-old male, who presented with a 2-year history of progressing neurological deficits starting with headaches, muscle pain and weight loss. Nine months later, the patient had developed two generalized epileptic seizures, optic and acoustic hallucinations, oculomotor disturbances, gait ataxia and signs of polyneuropathy. Over time, investigations in external hospitals had led to the assumption of an autoimmune encephalitis according to the following findings: a T2-sequence hyperintense alteration of the right hippocampus in the magnetic resonance imaging (MRI), positive oligoclonal bands but normal cell count in the cerebrospinal fluid, and positive serum tests for Anti-Huand N-Methyl-D-aspartic acid-receptor (NMDA-R) antibodies. Serum antibodies against acetycholine receptors and repeated tumor search remained negative. Treatments with prednisolone, intravenous immunglobuline and plasmapheresis were not effective. On clinical examination we saw a 32-year-old, cachectic and wheelchair bound patient with complex oculomotor disturbances including an anisocoric, converged right pupil with disturbed abduction and a dysfunction of horizontal movements of both eyes. There were signs of dysphagia and dysphonia. Severe generalized muscle atrophy and muscle pain were accompanied by pareses focused on the muscles of the neck causing a dropped head, but pareses were also found in the muscles of the proximal upper limb region and the distal lower limbs. Severe gait and limb ataxia and signs of polyneuropathy predominantly of the lower limbs including pallhypaesthesia and arreflexia made it impossible for the patient to stand or walk. Considering the fast progression of symptoms several diagnostics were repeated: cerebral MRI (1.5 T) showed an unchanged T2-hyperintense, non-contrast enhancing signal alteration of the right hippocampal area (Fig. 1). The patient’s serum was again tested positive (Indirect immunofluorescence test [2], Euroimmun Medical Laboratory Diagnostics, Luebeck, Germany) for anti-Hu-antibodies (titre 1:1,000, reference \1:10) and NMDA-R antibodies (titre 1:320, reference\1:10). The patient denied repetition of lumbar puncture at this point. Electroneurography demonstrated a mostly demyelinating sensorimotor I. Pohley M. Wittstock R. Benecke A. Wolters Department of Neurology, University of Rostock, Rostock, Germany