Paraneoplastic Opsoclonus Myoclonus 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 Opsoclonus-Myoclonus Syndrome Associated with Non-Small Cell Lung Cancer.

Paraneoplastic Opsoclonus-Myoclonus Syndrome Associated with Non-Small Cell Lung Cancer.

Anti-Ma paraneoplastic opsoclonus–myoclonus syndrome

A 73-year-old woman with hypertension, type 2 diabetes and a 25 pack-year smoking history presented to the hospital with a 2-month history of dizziness, diplopia, memory loss, ataxia, insomnia and...

Diagnostic values of 68Ga-labelled DOTANOC PET/CT imaging in pediatric patients presenting with paraneoplastic opsoclonus myoclonus ataxia syndrome.

Opsoclonus myoclonus ataxia (OMA) syndrome, also known as "Kinsbourne syndrome" or "dancing eye syndrome," is a rare, paraneoplastic entity which may be associated with pediatric neuroblastic tumors and carry a grave prognosis. We aimed to evaluate the role of 68Ga DOTANOC PET/CT for detecting neuroblastic tumors in patients with OMA syndrome. We retrospectively evaluated the 68Ga-DOTANOC PET/CT data of pediatric patients presenting with OMA syndrome from March 2012 to November 2018. A somatostatin receptor (SSTR)-expressing lesion with corresponding morphological change on CT image was considered PET-positive, while no abnormal SSTR expression or lesion was noticed in PET-negative patients. Histopathology and/or clinical/imaging follow-up (minimum one year) was considered a reference standard for comparing the PET/CT findings. The results of 68Ga-DOTANOC PET/CT were also compared with 131I MIBG whole-body scintigraphy, which was available in five patients. Of 38 patients (13 males, 25 females, aged 3-96 months), 18 (47.3%) had SSTR-expressing lesions (PET-positive), and histopathology revealed neuroblastic tumors in 17/18 lesions (neuroblastoma 14, ganglioneuroblastoma 2, and ganglioneuroma 1) and reactive hyperplasia in 1/18. The remaining 20/38 (52.6%) patients did not demonstrate SSTR-expressing lesions (PET-negative) and had an uneventful follow-up. The average SUVmax of the PET-positive lesions was 10.3 (range 2.8-34.5). The PET/CT results revealed 17 true-positive, one false-positive, 20 true-negative, and zero false-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100%, 95.2%, 94.4%, 100%, and 97.3% respectively. 68Ga-DOTANOC PET/CT identified neuroblastic tumors with a high diagnostic accuracy in our cohort compared to histology and follow-up. • Opsoclonus myoclonus ataxia (OMA) syndrome or "dancing eye syndrome" is a rare paraneoplastic entity which may be associated with pediatric neuroblastic tumors with a grave prognosis. • 123I/131I MIBG imaging has a proven role for functional imaging in neuroblastoma or patients with OMA, but the role of 68Ga-DOTANOC PET/CT is not yet studied. • 68Ga-labelled DOTANOC PET/CT (SSTR) imaging, in our cohort, was able to positively identify neuroblastic tumors with high diagnostic accuracy when compared with histology.

Paraneoplastic Opsoclonus-Myoclonus Syndrome As Presenting Symptom of Primary Gallbladder Adenocarcinoma (2632)

Paraneoplastic Opsoclonus-Myoclonus Syndrome As Presenting Symptom of Primary Gallbladder Adenocarcinoma (2632)

A rare case of paraneoplastic opsoclonus myoclonus syndrome that developed during chronic maintenance hemodialysis

A rare case of paraneoplastic opsoclonus myoclonus syndrome that developed during chronic maintenance hemodialysis

Ofatumumab for a rituximab‐allergic child with chronic‐relapsing paraneoplastic opsoclonus–myoclonus

Ofatumumab is a fully human anti-CD20 monoclonal antibody in phase II-III trials for various autoimmune and lymphoreticular diseases. We used it to treat a rituximab-allergic child with severe, chronic-relapsing, opsoclonus-myoclonus syndrome (OMS), characterized by persistent cerebrospinal fluid (CSF) B-cell expansion and T-cell dysregulation. He had relapsed despite chemotherapy, plasma exchange with immunoadsorption, and resection of ganglioneuroblastoma, detected 3 years after OMS onset. The four ofatumumab infusions (1,195 mg/m(2) total dose) were well tolerated, and CSF B-cell expansion was eliminated. No further relapses have occurred in 3 years, but he remains on low-dose ACTH with neuropsychiatric residuals of OMS.

Paraneoplastic Opsoclonus-Myoclonus Syndrome as a New and Single Manifestation of Relapsing Disease in a Patient with Small Cell Lung Cancer

A 55-year-old woman smoker with a history of cough, weight loss, and chest pain, without neurologic complaints, presented with a mass in the right lung. A bronchoscopy revealed a tumor in the right intermediate bronchus. The biopsy of the lesion showed small cell carcinoma. A FDGpositron emission tomography (PET)-computed tomography (CT) scan was performed and is displayed in Figure 1A. A brain CT was normal. After the diagnosis of limited-stage small cell lung cancer, the patient was treated with four cycles of cisplatin and etoposide combined with normofractionated thoracic radiotherapy (55 Gy) concurrent with the last two cycles. A radiological complete response was assessed, and treatment was completed with prophylactic cranial irradiation. Seven months after complete response, the patient experienced rapidly progressive dizziness and gait instability, followed by gaze disturbances and involuntary, continuous, conjugate, and chaotic saccadic eye movements. The gait disorder worsened, leaving the patient absolutely bedridden. On examination, intermittent myoclonic movements were apparent in the limbs and trunk (see video, part 1, Supplemental Digital Content 1, http://links.lww.com/JTO/A73, which shows these findings). She had neither cognitive impairment nor motor/sensory losses. Brain magnetic resonance imaging and cerebrospinal fluid examination were without noteworthy alterations. Serum antineuronal antibodies (antiHu, anti-Ri, anti-CV2, and antiamphiphysin) were negative. She was diagnosed with opsoclonus-myoclonus syndrome (OMS), and intravenous corticoids were administered for 5 days without improvement. There was no evidence of relapse on the chest CT, and the patient refused a bronchoscopy. A positron emission tomography-CT examination was strictly normal (Figure 1B). Although there was no visible tumor, we considered OMS as its herald, and second-line chemotherapy was started with carboplatin and etoposide in an attempt to reverse her devastating neurologic condition. After just the first cycle, opsoclonus and gait instability improved and the myoclonus resolved completely (see video, part 2, Supplemental Digital Content 1, http://links.lww.com/JTO/A73, which demonstrates her clinical improvement). The patient has completed three cycles of chemotherapy and continued free of recurrence for a total of 31 months, when a right supraclavicular relapse was detected and pathologically confirmed. Nevertheless, paraneoplastic neurologic symptoms did not recur, and third-line chemotherapy with oral topotecan was started.

Screening for tumours in paraneoplastic syndromes: report of an EFNS Task Force

paraneoplastic neurological syndromes (PNS) almost invariably predate detection of the malignancy. Screening for tumours is important in PNS as the tumour directly affects prognosis and treatment and should be performed as soon as possible. an overview of the screening of tumours related to classical PNS is given. Small cell lung cancer, thymoma, breast cancer, ovarian carcinoma and teratoma and testicular tumours are described in relation to paraneoplastic limbic encephalitis, subacute sensory neuronopathy, subacute autonomic neuropathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome (LEMS), myasthenia gravis and paraneoplastic peripheral nerve hyperexcitability. many studies with class IV evidence were available; one study reached level III evidence. No evidence-based recommendations grade A-C were possible, but good practice points were agreed by consensus. the nature of antibody, and to a lesser extent the clinical syndrome, determines the risk and type of an underlying malignancy. For screening of the thoracic region, a CT-thorax is recommended, which if negative is followed by fluorodeoxyglucose-positron emission tomography (FDG-PET). Breast cancer is screened for by mammography, followed by MRI. For the pelvic region, ultrasound (US) is the investigation of first choice followed by CT. Dermatomyositis patients should have CT-thorax/abdomen, US of the pelvic region and mammography in women, US of testes in men under 50 years and colonoscopy in men and women over 50. If primary screening is negative, repeat screening after 3-6 months and screen every 6 months up till 4 years. In LEMS, screening for 2 years is sufficient. In syndromes where only a subgroup of patients have a malignancy, tumour markers have additional value to predict a probable malignancy.

Paraneoplastic opsoclonus–myoclonus syndrome secondary to immature ovarian teratoma

Paraneoplastic neurologic complications from gynecologic tumors are rare, but can be a major cause of morbidity and mortality. In most cases, the neurologic symptoms precede the diagnosis of malignancy, prompting an evaluation that identifies the tumor. Paraneoplastic opsoclonus–myoclonus syndrome, characterized by saccadic eye movements caused by lesions in the brain stem, has in particular been linked to ovarian teratomas.

Clonazepam responsive opsoclonus myoclonus syndrome: additional evidence in favour of fastigial nucleus disinhibition hypothesis?

Opsoclonus myoclonus syndrome is a rare paraneoplastic syndrome seen in 50% of children with neuroblastoma. Neural generator of opsoclonus and myoclonus is not known but evidences suggest the role of fastigial nucleus disinhibition from the loss of function of inhibitory (GABAergic) Purkinje cells in the cerebellum. We present a child with paraneoplastic opsoclonus myoclonus syndrome who responded well to clonazepam. Response to clonazepam is an evidence for the involvement of GABAergic neural circuits in the genesis of opsoclonus myoclonus syndrome and is in agreement with fastigial nucleus disinhibition hypothesis.

Anti-Ri-associated paraneoplastic cerebellar degeneration and breast cancer: An autopsy case study

Several antineuronal antibodies are associated with paraneoplastic cerebellar degeneration. Anti-Ri is one of these antibodies in some cases but it is more commonly associated with paraneoplastic opsoclonus myoclonus in the context of gynecological neoplasia. Anti-Ri autoantibodies are thought to be directed against onconeural antigens, NOVA-1 and NOVA-2, that are expressed by the tumor as well as by neurons. The results of the treatment of both syndromes have been disappointing, although aggressive multimodality immunosuppressive treatments have been used. There are few cases of anti-Ri paraneoplastic cerebellar degeneration and none has been pathologically studied. We report the pathological study of a patient who died from anti-Ri-positive paraneoplastic cerebellar degeneration associated with breast cancer only confirmed at autopsy.

SnapShot: The Splicing Regulatory Machinery

organisms (it is estimated that more than two-thirds of human multiexon genes undergo alternative splicing) as well as the large number of RNA-binding domain proteins and other potential trans-acting factors that currently lack assigned functions, we anticipate the list of important splicing regulators to greatly expand in the next several years. Abbreviations Protein domains: C2HC Znf, CCHC zinc finger domain; C3H1 Znf, CCCH zinc finger domain; G Patch, glycine-rich nucleic binding domain; HEAT, HEAT repeats; GY, glycineand tyrosine-rich domain; GYR, glycine-, tyrosine-, and arginine-rich domain; KH, RNA-binding domain; PWI, PWI nucleic acid-binding domain; RGG, RGG box: arginineglycine-glycine repeats; RRM, RNA recognition motif; RS, arginine-serine repeats-containing domain; SWAP, RNA-binding domain derived from the Drosophila Suppressorof-White-APricot splicing regulator; SRGY, motif enriched in serine, arginine, glycine, and tyrosine. Binding sites: […], spacer sequence of 1 to 20 nucleotides; n, motif repetitions; ND, not determined; R, purine; Y, pyrimidine. Mouse phenotypes and disease associations: −/−, homozygous knockout; −/+, heterozygous knockout; CNS, central nervous system; Cond. KO, conditional knockout; BD, Becker muscular dystrophy; DD, Duchenne muscular dystrophy; LS, Leigh’s syndrome; MD, Myotonic dystrophy; PE, Paraneoplastic Encephalomyelitis; PNS, peripheral nervous system, POMA, Paraneoplastic Opsoclonus-Myoclonus Ataxia; RA, retinoic acid; SCZ, Schizophrenia. Mouse tissues: Amy, amygdala; Ceb, cerebellum; Hip, hippocampus; Hyp, hypothalamus; OB, olfactory bulb; SC, spinal cord; BM, bone marrow; Bo, bone; Ht, heart; SM, skeletal muscle; Epd, epidermis; Kd, kidney; Liv, liver; Lu, lung; Pan, pancreas; Pla, placenta; Pro, prostate; Sto, stomach; Spl, spleen; Thy, thymus; Thd, thyroid; Te, testis; Ut, uterus; Ov, ovary; E3.5, embryo day 3.5; E6.5, embryo day 6.5; E8.5, embryo day 8.5; E10.5, embryo day 10.5. Data Analysis The mouse mRNA expression profiles were generated using the TreeView v1.60 program and microarray data from the study of Su et al. (2002). The color scale indicates signal intensity over the mean intensity value for the 28 tissues shown. The mean-subtracted intensity values range from −606.9 to +7680.7.

Long-Term Survival in Paraneoplastic Opsoclonus-Myoclonus Syndrome Associated With Small Cell Lung Cancer

Paraneoplastic opsoclonus-myoclonus syndrome (OMS) is associated with small cell lung cancer (SCLC) in adults. Without appropriate treatment for SCLC, all reported patients with SCLC and OMS have died of complications of OMS within 3 months of diagnosis. With appropriate treatment, about half of reported patients have had improvement in neurologic function, and several have become long-term survivors (6-84 months). We report a patient with SCLC who presented with OMS and was refractory to immunosuppressive therapy but responded rapidly to antineoplastic therapy and remains alive with no sign of SCLC recurrence and minimal residual neurologic deficits 30 months after diagnosis. In patients presenting with OMS, early recognition and treatment of the underlying malignancy probably improve the chances for recovery from the OMS with minimal deficit and ultimate survival.

Management of paraneoplastic neurological syndromes: report of an EFNS Task Force

Paraneoplastic neurological syndromes (PNS) are remote effects of cancer on the nervous system. An overview of the management of classical PNS, i.e. paraneoplastic limbic encephalitis, subacute sensory neuronopathy, paraneoplastic cerebellar degeneration, paraneoplastic opsoclonus-myoclonus, Lambert-Eaton myasthenic syndrome and paraneoplastic peripheral nerve hyperexcitability is given. Myasthenia gravis and paraproteinemic neuropathies are not included in this report. No evidence-based recommendations were possible, but good practice points were agreed by consensus. Urgent investigation is indicated, especially in central nervous system (CNS) syndromes, to allow tumour therapy to be started early and prevent progressive neuronal death and irreversible disability. Onconeural antibodies are of great importance in the investigation of PNS and can be used to focus tumour search. PDG-PET is useful if the initial radiological tumour screen is negative. Early detection and treatment of the tumour is the approach that seems to offer the greatest chance for PNS stabilization. Immune therapy usually has no or modest effect on the CNS syndromes, whereas such therapy is beneficial for PNS affecting the neuromuscular junction. Symptomatic therapy should be offered to all patients with PNS.

Post-streptococcal opsoclonus-myoclonus syndrome associated with anti-neuroleukin antibodies

Background: Adult opsoclonus-myoclonus (OM), a disorder of eye movements accompanied by myoclonus affecting the trunk, limbs, or head, is commonly associated with an underlying malignancy or precipitated by viral infection....

Common Molecular Pathways Mediate Long-Term Potentiation of Synaptic Excitation and Slow Synaptic Inhibition

Synaptic plasticity, the cellular correlate for learning and memory, involves signaling cascades in the dendritic spine. Extensive studies have shown that long-term potentiation (LTP) of the excitatory postsynaptic current (EPSC) through glutamate receptors is induced by activation of N-methyl-D-asparate receptor (NMDA-R)--the coincidence detector--and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Here we report that the same signaling pathway in the postsynaptic CA1 pyramidal neuron also causes LTP of the slow inhibitory postsynaptic current (sIPSC) mediated by metabotropic GABA(B) receptors (GABA(B)-Rs) and G protein-activated inwardly rectifying K(+) (GIRK) channels, both residing in dendritic spines as well as shafts. Indicative of intriguing differences in the regulatory mechanisms for excitatory and inhibitory synaptic plasticity, LTP of sIPSC but not EPSC was abolished in mice lacking Nova-2, a neuronal-specific RNA binding protein that is an autoimmune target in paraneoplastic opsoclonus myoclonus ataxia (POMA) patients with latent cancer, reduced inhibitory control of movements, and dementia.

Immunophenotype of Blood Lymphocytes in Neuroblastoma-Associated Opsoclonus-Myoclonus

To determine whether the distribution of peripheral blood mononuclear cells (PBMCs) is altered in paraneoplastic opsoclonus-myoclonus (POM). PBMCs from 17 children with POM, 17 children with OM but no tumor, and 17 controls were immunophenotyped using a comprehensive panel of surface markers by dual-laser flow cytometry. All groups were matched for age and gender; POM and OM patients were matched for treatment. In the POM patients, the CD4+ T-cell subset was smaller in both relative size (-18%, P = 0.02) and absolute size (-41%, P = 0.03) compared with controls. The CD4/CD8 ratio also was less (-29% to -44%) and was related to POM duration (P = 0.03). The absolute but not relative size of the gammadelta T-cell subset was reduced (-44%, P = 0.02). There were no significant abnormalities of CD19+ B-cells, CD3- or CD3+ NK cells, HLA-DR+ or CD25+ T-cells, or CD45RA+ or CD45RO+ T-cells. Prior tumor chemotherapy, which was associated with a higher percentage but not number of CD8+ T-cells, did not restore the CD4+ T-cell subset. When the POM and OM groups, which were not significantly different, were combined, chemotherapy decreased both the relative and absolute size of the CD19+ B-cell pool and had small effects on other lymphocyte subsets. POM is characterized by T-cell abnormalities of PBMCs, the most robust of which is reduction of the CD4+ T-cell subset and the CD4/CD8 ratio. Although this reduction was found previously in cerebrospinal fluid in POM patients, PBMC subsets did not otherwise reflect cerebrospinal fluid abnormalities. Longitudinal studies will be necessary to determine whether PBMC abnormalities could serve as treatment markers.

RNA Binding Proteins and the Control of Motor Activity

RNA binding proteins can play important roles in gene regulation and are also associated with a large number of human diseases. Identifying the sets of RNAs to which these proteins bind is critical to understanding their normal functions and roles in disease . Nova is a tissue-specific splicing factor involved in the disease paraneoplastic opsoclonus myoclonus ataxia (POMA), in which patients cannot inhibit movement and suffer uncontrollable shaking. Ule et al. developed an ultraviolet cross-linking and immunoprecipitation method to purify Nova-RNA complexes. Nova regulates a set of RNA targets that code for proteins involved in neuronal inhibition or that function at the synapse, consistent with POMA's being a disorder of motor inhibition. J. Ule, K. B. Jensen, M. Ruggiu, A. Mele, A. Ule, R. B. Darnell, CLIP identifies Nova-regulated RNA networks in the brain. Science 302 , 1212-1215 (2003). [Abstract] [Full Text]

CLIP identifies Nova-regulated RNA networks in the brain.

Nova proteins are neuron-specific antigens targeted in paraneoplastic opsoclonus myoclonus ataxia (POMA), an autoimmune neurologic disease characterized by abnormal motor inhibition. Nova proteins regulate neuronal pre-messenger RNA splicing by directly binding to RNA. To identify Nova RNA targets, we developed a method to purify protein-RNA complexes from mouse brain with the use of ultraviolet cross-linking and immunoprecipitation (CLIP).Thirty-four transcripts were identified multiple times by Nova CLIP.Three-quarters of these encode proteins that function at the neuronal synapse, and one-third are involved in neuronal inhibition.Splicing targets confirmed in Nova-/- mice include c-Jun N-terminal kinase 2, neogenin, and gephyrin; the latter encodes a protein that clusters inhibitory gamma-aminobutyric acid and glycine receptors, two previously identified Nova splicing targets.Thus, CLIP reveals that Nova coordinately regulates a biologically coherent set of RNAs encoding multiple components of the inhibitory synapse, an observation that may relate to the cause of abnormal motor inhibition in POMA.