Orthostatic myoclonus associated with Caspr2 antibodies.
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ABSTRACT:
SUBMITTER: Govert F
PROVIDER: S-EPMC4826340 | biostudies-literature | 2016 Apr
REPOSITORIES: biostudies-literature
Publications
Orthostatic myoclonus associated with Caspr2 antibodies.
Gövert Felix F Witt Karsten K Erro Roberto R Hellriegel Helge H Paschen Steffen S Martinez-Hernandez Eugenia E Wandinger Klaus-Peter KP Deuschl Günther G Dalmau Josep J Leypoldt Frank F
Neurology 20160304 14
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Project description:BackgroundAdult 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.MethodsWe present the first two reports of post-streptococcal OM associated with antibodies against a 56 kDa protein. Two young girls presented with opsoclonus and myoclonus following a febrile illness and pharyngitis. Protein purification techniques were employed. Amino acid sequences of human neuroleukin (NLK) and streptococcal proteins were compared using the protein-protein BLAST application.ResultsThe antigen was identified as NLK (glucose-6-phosphate isomerase, GPI). GPI is present on the cell surface of streptococcus making the protein a candidate target for molecular mimicry.ConclusionsWe have identified NLK as an antigenic target in two patients with post-streptococcal OM. The pathogenicity of the antibodies is uncertain. The potential role of anti-neuroleukin antibodies in the pathogenesis of OM is discussed. We propose that OM may represent a further syndrome in the growing spectrum of post-streptococcal neurological disorders. The role of streptococcus in OM and the frequency with which anti-NLK responses occur in both post-infectious and paraneoplastic OM should be investigated further.
| S-EPMC2077526 | biostudies-literature
Project description:BACKGROUND:Orthostatic tremor (OT) and orthostatic myoclonus (OM) are weight-bearing hyperkinetic movement disorders most commonly affecting older people that induce "shaky legs" upon standing. OT is divided into "classical" and "slow" forms based on tremor frequency. In this paper, the first joint review of OT and OM, we review the literature and compare and contrast their demographic, clinical, electrophysiological, neuroimaging, pathophysiological, and treatment characteristics. METHODS:A PubMed search up to July 2016 using the phrases "orthostatic tremor," "orthostatic myoclonus," "shaky legs," and "shaky legs syndrome" was performed. RESULTS:OT and OM should be suspected in older patients reporting unsteadiness with prolonged standing and/or who exhibit cautious, wide-based gaits. Surface electromyography (SEMG) is necessary to verify the diagnoses. Functional neuroimaging and electrophysiology suggest the generator of classical OT lies within the cerebellothalamocortical network. For OM, and possibly slow OT, the frontal, subcortical cerebrum is the most likely origin. Clonazepam is the most useful medication for classical OT, and levetiracetam for OM, although results are often disappointing. Deep brain stimulation appears promising for classical OT. Rolling walkers reliably improve gait affected by these disorders, as both OT and OM attenuate when weight is transferred from the legs to the arms. DISCUSSION:Orthostatic hyperkinesias are likely underdiagnosed, as SEMG is often unavailable in clinical practice, and thus may be more frequent than currently recognized. The shared weight-bearing induction of OT and OM may indicate a common pathophysiology. Further research, including use of animal models, is necessary to better define the prevalence and pathophysiology of OT and OM, in order to improve their treatment, and provide additional insights into basic balance and gait mechanisms.
| S-EPMC5233784 | biostudies-other
Project description:This letter was written in response to: Ramdhani RA, Frucht SJ. Isolated chorea associated with LGI1 antibody. Tremor Other Hyperkinet Mov. 2014; 4. doi: 10.7916/D8MG7MFC.
| S-EPMC4039192 | biostudies-literature
Project description:To review the electrophysiological and clinical characteristics of 32 patients with orthostatic myoclonus (OM), a relatively newly identified movement disorder, and compare these characteristics to those of primary orthostatic tremor (OT) patients and patients with similar gait and balance complaints without either hyperkinesia diagnosed during the same 30-month period.The database of the Mayo Clinic Florida Movement Disorders Electrophysiology Laboratory (MDEL) was searched for all patients referred for possible OM or OT from 6/2010 to 12/2012. All available clinical records and archived surface electromyographical data for these patients were reviewed and analyzed.32 patients with OM (mean age 74 years), 8 with primary OT (mean age 71), and 55 with neither orthostatic hyperkinesia (NOH) (mean age 68) were identified. All OT patients and 84% each of OM and NOH patients complained of involuntary leg movements while standing, e.g., "shaking," "trembling," or "jerking." All OM and OT patients experienced symptomatic and electrophysiological abatement or attenuation of their leg hyperkinesias by leaning forward onto an object while standing.OM has some similarities to OT, including causing "shaky legs" subjectively in standing older patients. Novel data from this work include that, as in OT, OM essentially abates when patients remove their weight from their legs. This shared isometric phenomenon may reflect that OT and OM are on a pathophysiological continuum. Further, many patients who complain of their legs "shaking" while standing may have neither OT nor OM. Surface electromyography may be a useful adjunct in extrapolating patients complaining of "shaky legs."
| S-EPMC4125490 | biostudies-literature
Project description:This letter was written in reply to this letter to the editor: Vynogradova I, Savitski V, Heckmann JG. Hemichorea associated with CASPR2 antibody. Tremor Other Hyperkinet Mov. 2014; 4. doi: 10.7916/D8VM49C5. The above letter to the editor was written in response to this article: Ramdhani RA, Frucht SJ. Isolated Chorea Associated with LGI1 Antibody. Tremor Other Hyperkinet Mov. 2014; 4. doi: 10.7916/D8MG7MFC.
| S-EPMC4039211 | biostudies-other
Project description:ObjectiveTo report a large cohort of patients with antibodies against contactin-associated protein-like 2 (Caspr2) and provide the clinical spectrum of this disorder.MethodsSerum and CSF samples were assessed at 2 neuroimmunology centers in Barcelona and Rotterdam. Patients were included if Caspr2 antibodies were confirmed with 2 independent techniques, including brain immunohistochemistry and cell-based assay. Clinical information was obtained by the authors or provided by treating physicians after patients' informed consent.ResultsMedian age at symptom onset was 66 years. Of 38 patients, 34 were male. Median time to nadir of disease was 4 months (in 30% >1 year). The most frequent syndromes included limbic encephalitis (42%) and Morvan syndrome (29%). Seventy-seven percent of the patients had ≥3 of the following symptoms: encephalopathy (cognitive deficits/seizures), cerebellar dysfunction, peripheral nervous system hyperexcitability, dysautonomia, insomnia, neuropathic pain, or weight loss. A tumor, mostly thymoma, occurred in 19% of the patients. Immunoglobulin G4 subclass antibodies were present in all patients; 63% also had immunoglobulin G1 antibodies. Treatment response occurred in 93% of the patients and 25% had clinical relapses.ConclusionsCaspr2 antibodies associate with a treatable disorder that predominantly affects elderly men. The resulting syndrome may vary among patients but it usually includes a set of well-established symptoms. Recognition of this spectrum of symptoms and consideration of the protracted clinical course are important for early diagnosis of this disorder. Prompt immunotherapy and tumor therapy (if needed) often result in improvement.
| S-EPMC4970662 | biostudies-literature
Project description:ObjectiveA recent study showed glutamate receptor delta 2 antibodies (GluD2-ab) in sera of patients with opsoclonus-myoclonus syndrome (OMS). Inconsistencies between cerebellar immunoreactivity and expression of GluD2 led us to hypothesize that these antibodies are not biomarkers of OMS.MethodsSerum of 45 children with OMS (10 [22%] with neuroblastoma), 158 adults with OMS (53 [34%] with tumors), and 172 controls including 134 patients with several types of neurologic disorders, 18 with neuroblastoma without OMS, and 20 healthy participants were investigated. Antibodies were determined with 3 different techniques: (1) rat brain immunohistochemistry, (2) a live cell-based assay using a standard secondary antibody (2-step CBA), and (3) a similar CBA with a secondary and tertiary antibodies (3-step CBA). Two plasmids were used in the CBA studies. Three commercial GluD2-ab and 2 human sera with GluD2-ab served as controls for expression of GluD2.ResultsThe 3 commercial GluD2-ab showed predominant reactivity with the molecular and Purkinje cell layers (where GluD2 is highly enriched), and were also positive with the indicated CBAs. Substantially milder reactivity with brain tissue and CBA was obtained with the 2 control human sera containing GluD2-ab. None of the 203 patients with OMS and 172 controls showed immunoreactivities consistent with GluD2-abs. Compared with a standard 2-step CBA, the 3-step assay did not improve antibody detection and showed more frequent nonspecific reactivity that was not immunoabsorbed with GluD2.ConclusionWe did not find GluD2-ab in a large cohort of patients with OMS. GluD2-ab should not be considered diagnostic biomarkers of OMS.
| S-EPMC8055333 | biostudies-literature
Project description: Not available
| S-EPMC8440042 | biostudies-literature
Project description:ObjectiveTo identify neuronal surface antibodies in opsoclonus myoclonus ataxia syndrome (OMAS) using contemporary antigen discovery methodology.MethodsOMAS patient serum immunoglobulin G immunohistochemistry using age-equivalent rat cerebellar tissue was followed by immunoprecipitation, gel electrophoresis, and mass spectrometry. Data are available via ProteomeXchange (identifier PXD009578). This generated a list of potential neuronal surface cerebellar autoantigens. Live cell-based assays were used to confirm membrane-surface antigens and adsorb antigen-specific immunoglobulin Gs. The serologic results were compared to the clinical data.ResultsFour of the 6 OMAS sera tested bound rat cerebellar sections. Two of these sera with similar immunoreactivities were used in immunoprecipitation experiments using cerebellum from postnatal rat pups (P18). Mass spectrometry identified 12 cell-surface proteins, of which glutamate receptor δ2 (GluD2), a predominately cerebellar-expressed protein, was found at a 3-fold-higher concentration than the other 11 proteins. Antibodies to GluD2 were identified in 14/16 (87%) OMAS samples, compared with 5/139 (5%) pediatric and 1/38 (2.6%) adult serum controls (p < 0.0001), and in 2/4 sera from patients with neuroblastoma without neurologic features. Adsorption of positive OMAS sera against GluD2-transfected cells substantially reduced but did not eliminate reactivity toward cerebellar sections.ConclusionAutoantibodies to GluD2 are common in patients with OMAS, bind to surface determinants, and are potentially pathogenic.
| S-EPMC6107266 | biostudies-literature
Project description:BackgroundThe syndrome of progressive encephalopathy with limb rigidity has been historically termed progressive encephalomyelitis with rigidity and myoclonus (PERM) or stiff-person syndrome plus.MethodsThe case is presented of a previously healthy 28-year-old man with a rapidly fatal form of PERM developing over 2 months.ResultsSerum antibodies to both NMDA receptors (NMDAR) and glycine receptors (GlyR) were detected postmortem, and examination of the brain confirmed an autoimmune encephalomyelitis, with particular involvement of hippocampal pyramidal and cerebellar Purkinje cells and relative sparing of the neocortex. No evidence for an underlying systemic neoplasm was found.ConclusionThis case displayed not only the clinical features of PERM, previously associated with GlyR antibodies, but also some of the features associated with NMDAR antibodies. This unusual combination of antibodies may be responsible for the particularly progressive course and sudden death.
| S-EPMC3146306 | biostudies-literature