Axial Dystonia Mimicking Stiff Person Syndrome.
Ontology highlight
ABSTRACT:
SUBMITTER: Balint B
PROVIDER: S-EPMC6353533 | biostudies-literature | 2016 Mar-Apr
REPOSITORIES: biostudies-literature
Publications
Axial Dystonia Mimicking Stiff Person Syndrome.
Balint Bettina B Meinck Hans-Michael HM Bhatia Kailash P KP
Movement disorders clinical practice 20151114 2
Both isolated axial dystonia and stiff person syndrome (SPS) are rare conditions that can look deceivingly similar. Here, we present three cases of axial dystonia resembling SPS with video documentation in order to illustrate the phenomenological similarities. We discuss clinical and paraclinical approaches to help distinction with its obvious implications for further management. ...[more]
Similar Datasets
Project description:Stiff limb syndrome (SLS) is a focal variant of the spectrum of stiff person syndrome. Its presentation with stiffness, limb posturing, and freezing-of-gait (FOG)-like episodes, together with the relative rareness of the disorder, make it conceivable that SLS might be misdiagnosed as atypical parkinsonism, in particular, corticobasal syndrome (CBS). To illustrate this, we present two cases of established SLS resembling CBS and discuss the distinguishing features that may alert the clinician to the correct diagnosis, with its obvious therapeutic and prognostic implications.
| S-EPMC6183245 | biostudies-literature
Project description:IntroductionStiff-person syndrome (SPS) is manifested by fluctuating rigidity of axial musculature with painful episodic spasms due to simultaneous co-contraction of agonist and antagonist muscles. We present a case report and video illustrating response to treatment with rituximab.Materials and methodsCase description and video are provided. A literature search for other reports of treatment with rituximab was performed.ResultsNine cases in addition to our case were described. Substantial clinical benefit was reported in 7/9 (78%) cases. Four out of 9 (44%) cases displayed persistent anti-glutamic acid decarboxylase (GAD) antibody positivity.ConclusionRituximab is an important treatment strategy in SPS. The persistence of anti-GAD antibody positivity even with clinical remission remains to be elucidated.
| S-EPMC3383307 | biostudies-literature
Project description:Stiff-person syndrome (SPS) is an uncommon neurological disorder characterized by significant rigidity and muscle spasms primarily affecting the truncal and proximal musculature. Furthermore, a wide-based gait with functional impairment is generally seen. High-dose benzodiazepines or baclofen are widely considered the optimal initial therapy; however, major adverse effects often preclude adequate dosing. Refractory cases may be treated with intravenous immunoglobulins (IVIG), plasma exchange, or B-cell depletion with rituximab, although these are also associated with major, sometimes fatal, adverse reactions. Several reports have validated the safety and utility of botulinum injections in this setting, yet botulinum remains markedly underutilized in this cohort. Below, a case report and review of the literature show botulinum can decrease pain and stiffness, improve gait and balance, and decrease dependence on powerful systemic treatments in this group.
| S-EPMC6800926 | biostudies-literature
Project description:BackgroundAnxiety is a heterogeneous behavioral domain playing a role in a variety of neuropsychiatric diseases. While anxiety is the cardinal symptom in disorders such as panic disorder, co-morbid anxious behavior can occur in a variety of diseases. Stiff person syndrome (SPS) is a CNS disorder characterized by increased muscle tone and prominent agoraphobia and anxiety. Most patients have high-titer antibodies against glutamate decarboxylase (GAD) 65. The pathogenic role of these autoantibodies is unclear.Methodology/principal findingsWe re-investigated a 53 year old woman with SPS and profound anxiety for GABA-A receptor binding in the amygdala with (11)C-flumazenil PET scan and studied the potential pathogenic role of purified IgG from her plasma filtrates containing high-titer antibodies against GAD 65. We passively transferred the IgG fraction intrathecally into rats and analyzed the effects using behavioral and in vivo electrophysiological methods. In cell culture, we measured the effect of patient IgG on GABA release from hippocampal neurons. Repetitive intrathecal application of purified patient IgG in rats resulted in an anxious phenotype resembling the core symptoms of the patient. Patient IgG selectively bound to rat amygdala, hippocampus, and frontal cortical areas. In cultured rat hippocampal neurons, patient IgG inhibited GABA release. In line with these experimental results, the GABA-A receptor binding potential was reduced in the patient's amygdala/hippocampus complex. No motor abnormalities were found in recipient rats.Conclusion/significanceThe observations in rats after passive transfer lead us to propose that anxiety-like behavior can be induced in rats by passive transfer of IgG from a SPS patient positive for anti-GAD 65 antibodies. Anxiety, in this case, thus may be an antibody-mediated phenomenon with consecutive disturbance of GABAergic signaling in the amygdala region.
| S-EPMC3035624 | biostudies-literature
Project description:A 9-year-old female child presented with a history of falls, weight loss, diffuse leg pain, and progressive gait disorder, following 1 previous event described as a tonic-clonic seizure. She had increased thyroid volume, brisk symmetric reflexes, abnormal gait, and painful spasms of the paraspinal musculature. Thyroid function tests indicated biochemical hyperthyroidism, and thyrotropin receptor antibodies were positive. Her electromyography showed continuous activation of normal motor units of the paraspinal and proximal lower extremity muscles. The patient had a diagnosis of Graves' disease with associated stiff-person syndrome, with elevated anti-glutamic acid decarboxylase antibody levels. After intravenous immunoglobulin therapy, her ambulation was substantially improved and the symptoms of stiff-person syndrome decreased dramatically.
| S-EPMC5417285 | biostudies-literature
Project description:Glutamic acid decarboxylase 65 (GAD65) and autoantibodies specific for GAD65 (GADA) are associated with autoimmune diseases including Stiff Person Syndrome (SPS) and Type 1 diabetes (T1D). GADA is recognized as a biomarker of value for clinical diagnosis and prognostication in these diseases. Nonetheless, it remains medically interesting to develop sensitive and specific assays to detect GAD65 preceding GADA emergence, and to monitor GADA-GAD65 immune complexes in blood samples. In the present study, we developed a highly sensitive proximity ligation assay to measure serum GAD65. This novel assay allowed detection of as little as 0.65?pg/ml GAD65. We were also able to detect immune complexes involving GAD65 and GADA. Both free GAD65 and GAD65-GADA levels were significantly higher in serum samples from SPS patients compared to healthy controls. The proximity ligation assays applied for detection of GAD65 and its immune complexes may thus enable improved diagnosis and better understanding of SPS.
| S-EPMC4468815 | biostudies-other
Project description:IMPORTANCE:High titers of autoantibodies to glutamic acid decarboxylase (GAD) are well documented in association with stiff person syndrome (SPS). Glutamic acid decarboxylase is the rate-limiting enzyme in the synthesis of ?-aminobutyric acid (GABA), and impaired function of GABAergic neurons has been implicated in the pathogenesis of SPS. Autoantibodies to GAD might be the causative agent or a disease marker. OBJECTIVE:To investigate the characteristics and potential pathogenicity of GAD autoantibodies in patients with SPS and related disorders. DESIGN:Retrospective cohort study and laboratory investigation. SETTING:Weatherall Institute of Molecular Medicine, University of Oxford. PARTICIPANTS:Twenty-five patients with SPS and related conditions identified from the Neuroimmunology Service. EXPOSURES:Neurological examination, serological characterization and experimental studies. MAIN OUTCOMES AND MEASURES:Characterization of serum GAD antibodies from patients with SPS and evidence for potential pathogenicity. RESULTS:We detected GAD autoantibodies at a very high titer (median, 7500 U/mL) in 19 patients (76%), including all 12 patients with classic SPS. The GAD autoantibodies were high affinity (antibody dissociation constant, 0.06-0.78 nmol) and predominantly IgG1 subclass. The patients’ autoantibodies co-localized with GAD on immunohistochemistry and in permeabilized cultured cerebellar GABAergic neurons, as expected, but they also bound to the cell surface of unpermeabilized GABAergic neurons. Adsorption of the highest titer (700 000 U/mL) serum with recombinant GAD indicated that these neuronal surface antibodies were not directed against GAD itself. Although intraperitoneal injection of IgG purified from the 2 available GAD autoantibody–ositive purified IgG preparations did not produce clinical or pathological evidence of disease, SPS and control IgG were detected in specific regions of the mouse central nervous system, particularly around the lateral and fourth ventricles. CONCLUSIONS AND RELEVANCE:Autoantibodies to GAD are associated with antibodies that bind to the surface of GABAergic neurons and that could be pathogenic. Moreover, in mice, human IgG from the periphery gained access to relevant areas in the hippocampus and brainstem. Identification of the target of the non-GAD antibodies and peripheral and intrathecal transfer protocols, combined with adsorption studies, should be used to demonstrate the role of the non-GAD IgG in SPS.
| S-EPMC6055982 | biostudies-literature
Project description:BackgroundStiff-person syndrome (SPS), formerly Stiff-man syndrome, is a rare autoimmune disease usually exhibiting severe spasms and thoracolumbar stiffness, with very elevated glutamic acid decarboxylase antibodies (GAD Ab). A paraneoplastic variant, less well characterized, is associated with amphiphysin antibodies (amphiphysin Ab). The objective of this study was to identify distinctive clinical features of amphiphysin Ab-associated SPS.MethodsRecords associated with 845 sera tested in the Yale SPS project were examined, and 621 patients with clinically suspected SPS were included in the study. Clinical characteristics were assessed with correction for multiple comparisons.ResultsIn all, 116 patients had GAD antibodies and 11 patients had amphiphysin Ab; some clinical information was available for 112 and 11 of these patients, respectively. Patients with amphiphysin Ab-associated SPS were exclusively female; mean age was 60. All except one had breast cancer; none had diabetes. Compared to patients with GAD Ab-associated SPS, those with amphiphysin Ab were older (p = 0.02) and showed a dramatically different stiffness pattern (p < 0.0000001) with cervical involvement more likely, p < or = 0.001. Electromyography showed continuous motor unit activity or was reported positive in eight. Benzodiazepines at high dose (average 50 mg/day diazepam) were partially effective. Four patients were steroid responsive and tumor excision with chemotherapy produced marked clinical improvement in three of five patients.ConclusionsAmphiphysin Ab-associated stiff-person syndrome is strongly associated with cervical region stiffness, female sex, breast cancer, advanced age, EMG abnormalities, and benzodiazepine responsiveness. The condition may respond to steroids and can dramatically improve with cancer treatment.
| S-EPMC2676978 | biostudies-literature
Project description:Stiff Person Syndrome (SPS) is a rare immune-mediated disabling neurological disorder characterised by muscle spasms and high GAD antibodies. There are only a few case reports of autologous haematopoietic stem cell transplantation (auto-HSCT) as a treatment for SPS.ObjectiveTo describe the UK experience of treating refractory SPS with auto-HSCT.MethodsBetween 2015 and 2019, 10 patients with SPS were referred to our institution for consideration of auto-HSCT. Eight patients were deemed suitable for autograft and four were treated. Of the treated patients, three had classical SPS and one had the progressive encephalomyelitis with rigidity and myoclonus variant. All patients were significantly disabled and had failed conventional immunosuppressive therapy. Patients were mobilised with Cyclophosphamide (Cy) 2 g/m2 + G-CSF and conditioned with Cy 200 mg/kg + ATG followed by auto-HSCT.ResultsDespite their significantly reduced performance status, all patients tolerated the procedure with no unexpected toxicities. Following autograft, all patients improved symptomatically and stopped all forms of immunosuppressive therapies. Two patients were able to ambulate independently from being wheelchair dependent. One patient's walking distance improved from 300 meters to 5 miles and one patient's ambulation improved from being confined to a wheelchair to be able to walk with a frame. Two patients became seronegative for anti-GAD antibodies and normalised their neurophysiological abnormalities.ConclusionsAuto-HSCT is an intensive but well tolerated and effective treatment option for patients with SPS refractory to conventional immunotherapy. Further work is warranted to optimise patient selection and establish the efficacy, long-term safety, and cost-effectiveness of this treatment.
| S-EPMC7815605 | biostudies-literature
Project description:OBJECTIVE:In stiff person syndrome (SPS), an antibody-mediated impaired ?-aminobutyric acidergic (GABAergic) neurotransmission is believed to cause muscle stiffness and spasms. Most patients improve with GABA-enhancing drugs and intravenous immunoglobulin, but some respond poorly and remain disabled. The need for more effective therapy prompted a trial with the anti-CD20 monoclonal antibody rituximab. METHODS:This was a placebo-controlled randomized trial of rituximab (2 biweekly infusions of 1g each). The primary outcome was a change in stiffness scores at 6 months. Secondary outcomes were changes in heightened-sensitivity and quality of life scores. Enrolling 24 patients was calculated to detect 50% change in stiffness scores. RESULTS:Randomization was balanced for age, sex, disease duration, and glutamic acid decarboxylase autoantibody titers. No significant changes were noted at 6 months after treatment in all outcomes. Specifically, no differences were noted in the stiffness index, the primary outcome, or sensitivity scores, the secondary outcome, at 3 or 6 months. Quality of life scores improved significantly (p?<?0.01) at 3 months in both groups, but not at 6 months, denoting an early placebo effect. Blinded self-assessment rating of the overall stiffness for individual patients revealed improvement in 4 patients in each group. At 6 months, improvement persisted in 1 patient in the placebo group versus 3 of 4 in the rituximab group, where these meaningful improvements were also captured by video recordings. INTERPRETATION:This is the largest controlled trial conducted in SPS patients and demonstrates no statistically significant difference in the efficacy measures between rituximab and placebo. Rituximab's lack of efficacy could be due to a considerable placebo effect; insensitivity of scales to quantify stiffness, especially in the less severely affected patients; or drug effectiveness in only a small patient subset. Ann Neurol 2017;82:271-277.
| S-EPMC5755707 | biostudies-literature