Supranuclear gaze palsy and opsoclonus after Diazinon poisoning

A 52 year old man developed a supranuclear gaze palsy and opsoclonus after Diazinon poisoning. The diagnosis was confirmed by low plasma and red blood cell cholinesterase activity and urine mass spectroscopy. Saccadic control may be mediated in part by acetylcholine. Opsoclonus in the setting of organophosphate intoxication may occur as a result of cholinergic excess which overactivates the fastigial nuclei.     

Cerebellar activation in opsoclonus: an fMRI study

It is controversial whether opsoclonus is a cerebellar or brainstem disorder. Two patients whose opsoclonus largely disappeared on eye closure underwent fMRI. A comparison of these two states revealed neither vermal nor brainstem activation but rather a bilateral activation in the deep cerebellar nuclei in excess of what the authors found in healthy subjects. The results support a crucial role of the fastigial nucleus in opsoclonus.     

Opsoclonus in adults. Report of three cases and review of the literature

Opsoclonus is a rare but distinctive disorder of ocular motility. Although there are many reported cases of opsoclonus in children, there is no large series of cases in adults. In recent years, three cases of opsoclonus in adults have been identified at the University of Iowa, Iowa City. Review of 55 other cases of opsoclonus in adults reported in the literature showed that adults over 40 years of age with onset of opsoclonus should be investigated fully for underlying malignancy. In younger adults with a history of a preceding influenzalike illness, viral titers (acute and convalescent) should be obtained. Also, younger adults should be investigated for other causes of opsoclonus, such as drug or toxin exposure. Treatment is directed toward correcting the underlying process.     

Paraneoplastic opsoclonus: a neuropathologic study of two cases

The association of opsoclonus and malignant neoplasia is infrequent. The clinical and neuropathological data of two patients in whom opsoclonus and ataxia developed 7 and 11 months before the detection of a bronchial carcinoma are reported. Loss of Purkinje cells, edema of dentate nucleus and peridental demyelination were the most important neuropathological findings; neither carcinomatous metastases nor inflammatory signs were found in the brain. From the review of the pathological reports of paraneoplastic opsoclonus, the following conclusions can be drawn: the changes in the cerebellum are produced by the paraneoplastic cerebellar degeneration and are unrelated to the origin of opsoclonus, which has other anatomic substrates; paraneoplastic opsoclonus is a "remote effect" of cancer with an inflammatory basis, for which neurotoxic and immunological mechanisms have been hypothesized.     

Post-infectious Opsoclonus and Reversible Magnetic Resonance Imaging Changes: A Case Report and Review of the Literatures

Purpose: Opsoclonus is a rare neurological disorder in adult. The etiology of opsoclonus includes parainfectious, paraneoplastic, toxic, and metabolic disorders. We reported an old female with post-infectious opsoclonus who had a benign clinical course and reversible brain MRI lesions, and its review of the literature. Case Report: A 67-year-old woman presented with opsoclonus and truncal ataxia for two weeks. The magnetic resonance imaging (MRI) showed the hyperintensity lesions in bilateral medial thalamus, hypothalamus, and tegmentum of pons on Fluid-attenuated inversion recovery (FLAIR) imaging. Investigations of neoplasm and autoimmune disorders showed negative findings. Clinical symptoms subsided in two-week duration and MRI abnormalities also disappeared one month later. Conclusion: A benign clinical course and reversible MRI lesions could be found in the patients with postinfectious opsoclonus such as our case. However, detailed investigations and long-term follow-up are needed to exclude paraneoplastic or other systemic and immunological disorders.     

Opsoclonus in a patient with Guillain-Barré syndrome

A 54 year-old woman showed the unusual association of a Guillain-Barré syndrome and opsoclonus, a rare eye movement characterized by involuntary bursts of jerking, ataxic and multidirectional saccades, without an intersaccadic interval. Since opsoclonus is a phenomenon described exclusively in CNS diseases, the case reported supports the hypothesis of CNS involvement in some cases of Guillain-Barré syndrome. The latter is generally considered an immune-mediated disease and an immune pathogenesis is also supposed in opsoclonus associated with systemic malignancies; besides, in the patient reported, the self-limiting nature of the disturbance and the lack of MRI lesions suggest that opsoclonus may result from an immune-related phenomenon causing a functional and transitory dysfunction of the CNS.     

Opsoclonia: oculographic study

Oculographic study of a case of opsoclonus associated with infectious meningoencephalitis was used to determine the criteria of definition of this abnormal ocular movement, distinguishing it from the other abnormal movements of flutter and dysmetria. The authors first discuss, on the basis of these recordings, the possible relationship between opsoclonus and myoclonia, and then the role of the cerebellum. The disturbances noted in the course of study of saccadian movement lead them to suggest the hypothesis of overall involvement of the saccadian oculomotor system. They stress the value of oculographic recording in better understanding the general mechanisms of saccadian movement and the pathogenesis of the various changes which may be encountered.     

An antineuronal autoantibody in paraneoplastic opsoclonus

Sera from 7 patients with paraneoplastic opsoclonus were examined for antineuronal autoantibodies. An antibody against neuronal nuclei was found in serum from a patient with breast cancer, opsoclonus, and ataxia. This antibody recognized 53- to 61-kDa and 79- to 84-kDa antigens in immunoblots of neurons. Antineuronal antibodies were not found in other patients with paraneoplastic opsoclonus.     

Opsoclonus: an early sign of neonatal herpes encephalitis

Preferential involvement of certain central nervous systems areas by specific viruses provides a valuable guide to the selection of antiviral agents. We report a neonate that developed opsoclonus 7 days prior to the diagnosis of herpes simplex type 2 cerebellitis. The course of the opsoclonus paralleled the clinical course and radiologic evolution of the infection. The purpose of this report is to describe opsoclonus as a possible early sign of herpes simplex type 2 central nervous system infection.     

Opsoclonus in three dimensions: oculographic, neuropathologic and modelling correlates

Opsoclonus is a dyskinesia consisting of involuntary, arrhythmic, chaotic, multidirectional saccades, without intersaccadic intervals. We used a magnetic scleral search coil technique to study opsoclonus in two patients with paraneoplastic complications of lung carcinoma. Eye movement recordings provided evidence that opsoclonus is a three-dimensional oscillation, consisting of torsional, horizontal, and vertical components. Torsional nystagmus was also present in one patient. Antineuronal antibody study revealed the presence of anti-Ta (Ma2 onco-neuronal antigen) antibodies in one patient, which had previously been associated only with paraneoplastic limbic encephalitis and brainstem dysfunction, but not opsoclonus, and only in patients with testicular or breast cancer. Neuropathologic examination revealed mild paraneoplastic encephalitis. Normal neurons identified in the nucleus raphe interpositus (rip) do not support postulated dysfunction of omnipause cells in the pathogenesis of opsoclonus. Computer simulation of a model of the saccadic system indicated that disinhibition of the oculomotor region of the fastigial nucleus (FOR) in the cerebellum can generate opsoclonus. Histopathological examination revealed inflammation and gliosis in the fastigial nucleus. This morphological finding is consistent with, but not necessary to confirm, damage to afferent projections to the FOR, as determined by the model. Malfunction of Purkinje cells in the dorsal vermis, which inhibit the FOR, may cause opsoclonus by disinhibiting it.     

Opsoclonus: Its clinical value.

Although the exact site of pathologic involvement and the pathogenesis remain uncertain, opsoclonus is an invaluable clinical sign that in it alone may herald an occult systemic malignancy. A thorough systematic evaluation should be undertaken to exclude an occult neoplasm in any patient who presents with opsoclonus unaccompanied by any other clinical sign.     

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.     

Opsoclonus myoclonus

Opsoclonus myoclonus is a rare autoimmune condition characterized by cerebellar degeneration. It occurs most often as a paraneoplastic syndrome when a cancer remote to the brain induces cerebellar dysfunction that is unrelated to metastases. Half of all cases occur in children with a neuroblastoma. Most adults with opsoclonus myoclonus have neoplastic, infectious, metabolic, or idiopathic etiologies. Signs of cerebellar dysfunction noted at presentation include opsoclonus, myoclonus and ataxia, hence the name "dancing eyes, dancing feet syndrome." Opsoclonus is characterized by rapid, involuntary eye movements that are dysrhythmic and uncoordinated.Neuronal damage is induced by antibodies usually related to the primary pathology. Treatment targets the etiology and also employs steroids, plasmapheresis, immunosuppressive agents, or other anti-inflammatory therapies. Children with opsoclonus myoclonus resulting from a neuroblastoma often retain neurological sequelae. Adult cases of opsoclonus myoclonus with idiopathic or infectious etiologies have a more favorable prognosis than those with neoplastic origins.     

Opsoclonus as a manifestation of Hashimoto’s encephalopathy

We present a 59-year-old male with early manifestation of opsoclonus associated with gait ataxia as a rare clinical presentation of Hashimoto’s encephalopathy. Empiric use of intravenous immunoglobulin followed by intravenous high dose methylprednisolone was initiated with subsequent remittance of opsoclonus, encephalopathy, ataxia, and tremor. Extensive workup for infectious, autoimmune, and paraneoplastic etiologies were undertaken and all studies were negative. Thyroglobulin antibodies (312 U/mL) and thyroid peroxidase antibodies (457 U/mL) were elevated (normal <60 U/mL) with a euthyroid state (thyroid stimulating hormone 3.13 μIU/mL). Three months after intravenous steroid therapy, the concentrations of thyroglobulin and thyroid peroxidase antibodies were retested and found to have decreased considerably. Thus, with steroid therapy, the patient’s opsoclonus and encephalopathy improved. We have presented a patient with a rare case of opsoclonus as the principal presenting feature of Hashimoto’s encephalopathy that was incompletely responsive to intravenous immunoglobulin and resolved with corticosteroids. This report underscores the importance for clinical practitioners to maintain a high index of suspicion for Hashimoto’s encephalopathy in cases of opsoclonus, especially when accompanied by an atypical presentation.     

Mumps-induced opsoclonus-myoclonus and ataxia

A 9-year-old boy manifested acute cerebellar ataxia associated with mumps infection. He developed opsoclonus, myoclonus, tremor, and truncal ataxia 7 days after mumps infection. Lumbar puncture revealed pleocytosis without elevation of protein; ELISA demonstrated an increased IgM titer of cerebrospinal fluid against mumps virus. From these results it was determined that acute cerebellar ataxia was induced by a direct invasion of mumps virus. Electroencephalography demonstrated normal background activity, although alpha-like activity appeared bilaterally in the frontal regions which was induced by eye closure and decreased by eye opening. Polygraphic electroencephalography revealed that the alpha-like activity corresponded to the ocular movement recorded above or lateral to the eyelids by electro-oculography; therefore, the alpha-like activity was considered to be derived from the opsoclonus which was secondary to cerebellar involvement. His neurologic symptoms improved gradually and resolved completely within 3 months after the onset of acute cerebellar ataxia.     

Opsoclonus-Myoclonus Syndrome in Acute Cerebellar Ataxia –Clinical and electrophysiological observations of an adult case–

This is a report of opsoclonus and somatic myoclonus associated with acute cerebellar ataxia. The cardinal feature is the acute onset, after the brief prodromal symptoms, such as nausea and vomiting, of dramatic cerebellar ataxia with opsoclonus and somatic myoclonus. The pathophysiological basis for this phenomenon is postulated.     

A novel treatment‐responsive encephalitis with frequent opsoclonus and teratoma

Among 249 patients with teratoma‐associated encephalitis, 211 had N‐methyl‐D‐aspartate receptor antibodies and 38 were negative for these antibodies. Whereas antibody‐positive patients rarely developed prominent brainstem–cerebellar symptoms, 22 (58%) antibody‐negative patients developed a brainstem–cerebellar syndrome, which in 45% occurred with opsoclonus. The median age of these patients was 28.5 years (range = 12–41), 91% were women, and 74% had full recovery after therapy and tumor resection. These findings uncover a novel phenotype of paraneoplastic opsoclonus that until recently was likely considered idiopathic or postinfectious. The triad of young age (teenager to young adult), systemic teratoma, and high response to treatment characterize this novel brainstem–cerebellar syndrome. ANN NEUROL 2014;75:435–441     

An update on opsoclonus

PURPOSE OF REVIEW: The aim of this article is to review opsoclonus, with particular emphasis on its immunopathogenesis and pathophysiology. RECENT FINDINGS: Infections (West Nile virus, Lyme disease), neoplasms (non-Hodgkin's lymphoma, renal adenocarcinoma), celiac disease, and allogeneic hematopoietic stem cell transplantation can cause opsoclonus. Newly identified autoantibodies include antineuroleukin, antigliadin, antiendomysial, and anti-CV2. Evidence suggests that the autoantigens of opsoclonus reside in postsynaptic density, or on the cell surface of neurons or neuroblastoma cells (where they exert antiproliferative and proapoptotic effects). Most patients, however, are seronegative for autoantibodies. Cell-mediated immunity may also play a role, with B and T-cell recruitment in the cerebrospinal fluid linked to neurological signs. Rituximab, an anti-CD20 monoclonal antibody, seems efficacious as an adjunctive therapy. Although changes in synaptic weighting of saccadic burst neuron circuits in the brainstem have been implicated, disinhibition of the fastigial nucleus in the cerebellum, or damage to afferent projections to the fastigial nucleus, is a more plausible pathophysiologic mechanism which is supported by functional magnetic resonance imaging findings in patients. SUMMARY: There is increasing recognition that both humoral and cell mediated immune mechanisms are involved in the pathogenesis of opsoclonus. Further studies are needed to further elucidate its immunopathogenesis and pathophysiology in order to develop novel and efficacious therapy.     

Cerebellar ataxia and opsoclonus as the initial manifestations of myoclonic encephalopathy associated with neuroblastoma

Cerebellar ataxia and opsoclonus were the initial manifestations of an associated neuroblastoma in a 20-month-old girl. Two months after the initial symptomatology, a physical examination revealed an abnormal mass palpable left to the midline. Urinary catecholamines were within normal limits. The child's neurological findings improved immediately after surgery, and steroid treatment and the follow-up on her after 2 years revealed normal general nad neurological development. The syndrome of myoclonic encephalopathy including cerebellar ataxia, myoclonus and opsoclonus, and its relationship to neuroblastoma is reviewed. Failure to recognize this association can result in delays in both diagnosis and treatment and could be fatal.