anti-Ri Antibodies Research Articles

Paraneoplastic opsoclonus-myoclonus syndrome as a rare presentation of parotid adenocarcinoma

Paraneoplastic Opsoclonus-Myoclonus Ataxia Syndrome (POMA) is a rare neurological condition that affects approximately 1 in 10,000,000 people annually. This syndrome is poorly understood and can lead to long-term cognitive, behavioral, and motor complications. Opsoclonus is characterized by involuntary, rapid, repetitive, multi-vectorial oscillations of the eyes occurring in all directions of gaze. It is accompanied by diffuse or focal body myoclonus and may or may not include ataxia and other cerebellar signs. POMA is typically a paraneoplastic syndrome associated with neuroblastoma in childhood and breast carcinoma or small-cell lung carcinoma in adults. Additionally, viral or toxic agents are known to play a role in its etiology, and the immune system is involved in the pathogenesis. We report a case of a 41-year-old man with anti-Ri antibody opsoclonus-myoclonus syndrome and parotid adenocarcinoma involvement. After diagnosing opsoclonus-myoclonus syndrome, the patient underwent multimodal immunotherapy treatment, resulting in partial remission of the neurological symptoms.

Paraneoplastic cerebellar degeneration preceding diagnosis of breast adenocarcinoma

We report a case of a 40 years old patient presenting with paraneoplastic cerebellar degeneration. The diagnosis was made based on the clinical picture of axial and appendicular ataxia, associated with findings on MRI and confirmed by the presence of anti-Yo and anti-Ri antibodies in cerebral spine fluid. From this diagnosis, the search for neoplasm began. An invasive carcinoma was then detected by breast biopsy. Surgical treatment was then carried out with subsequent chemotherapy and radiotherapy. With specific cancer treatment, there was a significant improvement in cerebellar symptoms. The case described shows the importance of the neurologist keeping paraneoplastic syndrome in mind in their differential diagnosis list for cerebellar symptoms and signs of insidious onset.

OA17 Rheumatoid meningitis - a rare complication of rheumatoid arthritis

Abstract Introduction A wide spectrum of neurological complications can occur in rheumatoid arthritis (RA) including peripheral neuropathy, mononeuritis multiplex and rheumatoid vasculitis. Cerebrovascular disease is also common. We describe a rare neurological complication of RA. Case description The patient was first diagnosed with seropositive RA in 2015 at the age of 68. His rheumatoid factor at presentation was 144 kIU/L and CCP antibodies >340 U/mL. His background include alcohol excess and obstructive sleep apnoea with peripheral neuropathy attributed to alcohol. Nerve conduction studies demonstrated axonal neuropathy. By 2016, he had achieved good disease control with combination methotrexate and sulfasalazine. In 2018, he was admitted to stroke services with right arm weakness and focal neurological deficit on examination. An urgent CT head showed possible right parietal extra dural haemmorhage. His CRP was <5, ESR 24 with a normal ANA. Borrelia, syphilis and HIV screening were normal. Anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Hu, anti-Yo and anti-Ri antibodies were all negative. Lumbar puncture revealed a normal glucose and red blood cells count but the CSF protein was raised at 851 mg/L with a lymphocyte count of 9/ul. Gram stain, culture, viral PCR for HSV, VZV, enterovirus, parechovirus and adenovirus were normal and CSF cytology demonstrated a lymphocyte pleocytosis. Subsequent contrast MRI head scan showed leptomeningeal enhancement with gadolinium contrast. MRI of the cervical spine and brachial plexus was normal and an EMG/NCS of the upper limb demonstrated an incidental ulnar nerve compression at the elbow. Following neurology input, the leptomeningeal enhancement was thought to represent rheumatoid meningitis (RM). He was treated with 1 mg/kg prednisolone and rituximab with prompt and complete recovery. He remains well from both the perspective of his RA and RM. Discussion RM is a rare form of aseptic meningitis. Aseptic meningitis is commonly defined as clinical and CSF evidence of meningeal inflammation in the absence of an infectious aetiology. The vast differential includes malignancies, drug-induced and autoimmune diseases, for example lupus and sarcoidosis. The diagnosis of RM requires a high index of suspicion as well as exclusion of other causes. Historically RM was diagnosed at post-mortem but MRI scanning means pre-mortem diagnosis is possible. It is considered rare but serious manifestation of RA. Case reports suggest RM usually occurs in those with long standing seropositive RA but RM has been described in the early stages of RA and even as a presenting feature. Peripheral disease activity does not correlate with occurrence of RM. The clinical presentations vary depending on the brain structure involved and can include motor or sensory deficits, cognitive disturbance and seizures. It may mimic many other conditions. Radiological findings will not distinguish RM from other causes of aseptic meningitis. CSF finding of lymphocytosis and rheumatoid factor (if available) may help distinguish RM from other causes. Meningeal biopsy can confirm the diagnosis. Due to the rarity of RM, there are no current guidelines on treatment. Historically, corticosteroids are the main induction agent. There are case reports highlighting possible success from the addition of cyclophosphamide and rituximab. Case series also highlight a significant mortality rate in excess of 60% even despite treatment. This may represent publication and historical bias. Key learning points Rheumatoid meningitis (RM) is a rare but serious complication of rheumatoid arthritis. RM may not correlate with disease activity nor disease duration. Diagnosis is a challenge due to its wide clinical phenotype as well as the non-specificity of imaging, lumbar puncture and serological findings. Treatment options are based on case reports and series and include corticosteroids, rituximab and cyclophosphamide.

Paraneoplastic Neurologic Syndromes with ANNA-2/anti-Ri: a Contrasting Story of Two Cases (P5-5.026)

Paraneoplastic Neurologic Syndromes with ANNA-2/anti-Ri: a Contrasting Story of Two Cases (P5-5.026)

Anti-SOX1 Antibody-positive Small-cell Lung Cancer That Triggered Opsoclonus.

A 72-year-old woman with opsoclonus visited our hospital and was diagnosed with small-cell lung cancer. Blood tests revealed anti-SOX1 antibodies, so the patient was diagnosed with paraneoplastic opsoclonus-myoclonus syndrome. After steroid pulse therapy was started, chemotherapy of treatment, the opsoclonus showed an improving trend. Anti-Ri and anti-Hu antibodies have been reported as autoantibodies associated with neoplastic opsoclonus-myoclonus syndrome; however, there are no such reports concerning anti-SOX1 antibody. Therefore, this is a valuable case.

Breast cancer-associated opsoclonus-myoclonus syndrome: a case report

BackgroundParaneoplastic neurological syndromes constitute rare neurological complications of malignant disease, manifesting in <1% of patients with cancer. Opsoclonus-myoclonus syndrome (OMS) presents with chaotic ocular saccades (opsoclonus), spontaneous muscular jerking (myoclonus) that may be accompanied by ataxia, strabismus, aphasia, or mutism. Its paraneoplastic variant in the adult is most commonly associated with small-cell lung cancer, followed by breast cancer. Importantly, neurological symptoms usually precede the diagnosis of breast cancer and tend to recure after its treatment.Case presentationA 43-year-old premenopausal Caucasian woman with a medical history of hypertension was admitted following an episode of focal seizure. This progressed to generalised tonic-clonic seizures and she was subsequently loaded with phenytoin, valproate, and levetiracetam. Initial workup included whole body CT scan, viral and autoimmune serology. The CT scan revealed an enhancing right axillary lymph node, which in combination with Anti-Ri antibody positivity raised the spectre of paraneoplastic OMS. MRI of the head revealed subtle nonspecific white matter signal change within the centrum semiovale without any mass lesions, while MRI of the spine was unremarkable. An uncomplicated right mastectomy and axillary lymph node clearance was performed: histopathology revealed a 9-mm, grade 2, oestrogen receptor-positive, progesterone receptor-negative (ER8, PR0), Her2-negative invasive ductal carcinoma, and 4/6 positive lymph nodes (T1b N2 M0). Two months later, she was readmitted with vertigo, diplopia, facial weakness, and ataxia, setting the diagnosis anti-Ri syndrome recurrence. MDT recommended mammogram and ultrasound of the left breast, which were normal. Subsequently, four months after initial discharge, she suffered another neurological recurrence; due to concomitant abdominal pain, PET-CT was performed demonstrating a hypermetabolic right ovarian focus. Bilateral salpingo-oophorectomy was performed as per gynaecology MDT and final histology showed normal tubes and ovaries. She has remained on remission since then, with a negative annual mammogram follow-up.ConclusionsIn conclusion, we report a case of OMS associated with breast cancer anti-Ri onconeural antibody. Its manifestations preceded the diagnosis of malignancy and it persisted after cancer treatment, underlining the importance for high clinical suspicion in cases of classical paraneoplastic neurological syndromes as well as the need for long-term clinical follow-up.

Evaluation of antineuronal antibodies and 8-OHdG in mothers of children with autism spectrum disorder: a case-control study

Objective The purpose of our study was to investigated the anti-Yo, anti-Hu, anti-Ri, anti-amphiphysin antibody levels and 8-OHdG in mothers of children with autism. Methods This study included 60 participants, 33 of whom were healthy mothers of 3–12-year-old children diagnosed with autism spectrum disorder (ASD) and the 27 others who constituted the control group, were healthy mothers with age-matched healthy children. Two groups were examined for plasma anti-Yo, anti-Hu, anti-amphiphysin and anti-Ri antibodies and, 8-OHdG levels. The participants were asked to accomplish a sociodemographic data form. The severity of ASD symptoms was evaluated according to the Childhood Autism Rating Scale (CARS). Results Anti-amphiphysin antibody levels and anti-Ri antibody positivity were significantly higher in the case group (p = 0.001; p = 0.027, respectively). The two groups did not significantly differ in terms of anti-Yo and anti-Hu antibody levels and in terms of 8-OHdG levels (p = 0.065; p = 0.099; p = 0.490, respectively). The two groups did not significantly differ in terms of sociodemographic data (p > 0.05). Conclusions According to the our study, maternal antineuronal antibodies, such as anti-amphiphysin and anti-Ri, may contribute to the risk of childhood autism. Studies with larger samples are needed. KEY POINTS Maternal factors associated with autism should be investigated in order to create early diagnosis and treatment opportunities for autism. Based on the importance of immunological and cerebellar pathologies in autism aetiology, we aimed to investigate antineuronal antibodies in mothers of children with autism. Maternal antineuronal antibodies, such as anti-amphiphysin and anti-Ri, may contribute to the risk of childhood autism. High anti-amphiphysin antibody levels in mothers of children with autism may also occur against the amphiphysin in the structure of the SrGAP3 gene, which is associated with autism.

Opsoclonus-myoclonus syndrome associated with anti Kelch-like protein-11 antibodies in a young female patient without cancer

Opsoclonus-myoclonus syndrome (OMS) is a rare neurological disorder. The pathogenesis is thought to be immune-mediated. In adults, it may be idiopathic or paraneoplastic in origin. However, most cases of paraneoplastic OMS in adults are not associated with well-characterized antibodies, except for a small subgroup who have anti-Ri antibodies. Herein, we provide the first detailed description of a case of OMS associated with a Kelch-like protein-11 antibody, a newly discovered biomarker for paraneoplastic neurological syndromes associated with germ-cell tumors. This was a young female patient in whom no tumor was ever detected and who had an excellent response to rituximab.

Distinctive MRI features of paraneoplastic encephalitis with anti-Ri antibodies

Distinctive MRI features of paraneoplastic encephalitis with anti-Ri antibodies

Differences and diversity of autoimmune encephalitis in 77 cases from a single tertiary care center

BackgroundThe incidence of autoimmune encephalitis has risen globally. There are two general categories of disease-associated antibodies that can be tested for: neuronal surface and intracellular. However, testing both groups of autoantibodies are costly. This study aims to identify differences between groups by comparing clinical presentations, radiological findings and CSF profile of patients, and determine if any parameters are indicative of one group of autoantibodies over another. Additionally, we aim to report the local incidence of less common groups of disease-associated antibodies as well.MethodsSeventy-seven records of autoimmune encephalitis/encephalomyelitis patients admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between October 2010 and February 2017 were reviewed. Patients with infections or those with classic central nervous system demyelinating features were excluded.ResultsOf 77 patients, 40% presented with neuronal surface antibodies and 33% had intracellular antibodies. The most common autoantibody detected in each group was anti-NMDAr antibody (25/31, 81%) and anti-Ri antibody (7/25, 28%) respectively. In the neuronal surface antibody group, behavioral change was the most common complaint (45%), followed by seizures (39%) and abnormal movements (29%). In the latter group, seizure was the most common presenting symptom (32%), followed by motor weakness (20%), behavioural change (16%) and abnormal movements (16%). Patients with neuronal surface antibodies were younger (35 vs 48 years old, p = 0.04) and more likely to present with behavioral change (45% vs 16%, p = 0.02). Mortality rate was higher in the intracellular group (16% vs 3.2%, p = 0.09). No differences were detected in magnetic resonance imaging (MRI) and CSF profile.ConclusionsIn the early stages of the disease, both groups have comparable clinical outcomes. Although there were significant differences in age and percentage of patients with behavioral change, both groups of autoimmune encephalitis still shared many clinical features and could not be distinguished based on MRI and CSF profiles. Therefore, we recommend that patients with features of autoimmune encephalitis should be screened for both the neuronal surface and intracellular antibodies regardless of clinical presentation.

Janus kinase 1/2 inhibition for the treatment of autoinflammation associated with heterozygous TNFAIP3 mutation

Janus kinase 1/2 inhibition for the treatment of autoinflammation associated with heterozygous TNFAIP3 mutation

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 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.

Concomitant Opsoclonus and Ataxia and Limbic Encephalitis due to Dual Anti-Ri and Anti-Yo Positive Antibodies (P4.239)

Concomitant Opsoclonus and Ataxia and Limbic Encephalitis due to Dual Anti-Ri and Anti-Yo Positive Antibodies (P4.239)

Anti-Ri antibody associated paraneoplastic brainstem and cerebellar dysfunction as the presenting sign of small cell lung carcinoma (P4.237)

Anti-Ri antibody associated paraneoplastic brainstem and cerebellar dysfunction as the presenting sign of small cell lung carcinoma (P4.237)

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

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

Anti-Ri-associated paraneoplastic brainstem cerebellar syndrome with coexisting limbic encephalitis in a patient with mixed large cell neuroendocrine lung carcinoma

Paraneoplastic neurologic syndromes (PNS) can be the first manifestations of occult malignancies. If left untreated, PNS often lead to significant morbidity and mortality. Anti-Ri (anti-neuronal nuclear antibody type 2 [ANNA-2]) autoantibodies are commonly associated with breast and small cell lung cancers. Cases of anti-Ri paraneoplastic cerebellar degeneration are reported, but few describe severe nausea and coexisting limbic encephalitis as the major presenting features. We report a 75-year-old woman with medically-intractable emesis, encephalopathy, diplopia, vertigo, and gait ataxia for 3months. Examination revealed rotary nystagmus, ocular skew deviation, limb dysmetria, and gait ataxia. After two courses of intravenous immunoglobulin, there was minimal improvement. Anti-Ri antibodies were positive in serum only. CT scan identified a 2.0cm left lung mass, and histopathology revealed large cell neuroendocrine carcinoma with admixed adenocarcinoma non-small cell lung carcinoma (NCSLC). Though the patient achieved nearly complete clinical recovery after tumor resection, anti-Ri levels remained high at 20months post-resection. To our knowledge this is the first report of a paraneoplastic brainstem cerebellar syndrome with coexisting limbic encephalitis involving anti-Ri positivity and associated mixed neuroendocrine/NSCLC of the lung with marked improvement after tumor resection.

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.

When the Typical Becomes Atypical: Anti-Ri Antibody Associated Paraneoplastic Syndrome WITHOUT Opsoclonus-Myoclonus (P7.024)

When the Typical Becomes Atypical: Anti-Ri Antibody Associated Paraneoplastic Syndrome WITHOUT Opsoclonus-Myoclonus (P7.024)

Anti-Ri Antibody Paraneoplastic Syndrome Without Opsoclonus-Myoclonus

Anti-Ri antibody paraneoplastic neurologic syndrome historically has been linked to ataxia, opsoclonus-myoclonus and brainstem encephalitis, but these “cardinal features” are not necessary for its diagnosis, which should be considered in patients with subacute course of heterogeneous neurological manifestations. This is a report of a man who suffers from anti-Ri antibody paraneoplastic syndrome, with an atypical clinical presentation. His syndromic diagnosis was confirmed by serum western blot analysis that revealed the presence of anti-Ri antibodies. Clues to the underlying malignancy were given by FDG-PET scan that demonstrated a hypermetabolic peripancreatic lymph node. Besides highlighting clinical features of anti-Ri antibody syndrome that will help its early recognition and the appropriate steps for its diagnosis, we also discuss various treatment modalities that should be considered in this population in order to improve morbidity and mortality. J Neurol Res. 2014;4(1):31-33 doi: http://dx.doi.org/10.14740/jnr261w