Case report: Approaches to treatment-refractory and super-refractory glutamic acid decarboxylase antibody-spectrum disorders.
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ABSTRACT: Background
Glutamic acid decarboxylase antibody-spectrum disorders (GAD-SDs) include a group of autoimmune neurological diseases associated with neuronal excitability, most noticeably stiff person syndrome. Immune modulators are the mainstay of treatment, but a significant number of patients remain refractory.Methods
We present our single-center experience of eight cases of GAD-SD, two of which were refractory to immune modulatory treatments.Results
Of the two cases that were refractory to immunomodulation, one showed significant improvement with bilateral globus pallidus interna deep brain stimulation (GPi DBS) placement, and the other showed significant improvement with autologous hematopoietic stem cell transplant (aHSCT).Discussion
To our knowledge, this is the first instance of GPi DBS placement being noted to improve GAD-SD movements.
SUBMITTER: Rajmohan R
PROVIDER: S-EPMC10800536 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
Case report: Approaches to treatment-refractory and super-refractory glutamic acid decarboxylase antibody-spectrum disorders.
Rajmohan Ravi R Baveja Shivali S Nguyen Dai D Shah Eshita E Sy Michael M Attaripour Sanaz S Swope David D
Frontiers in immunology 20240108
<h4>Background</h4>Glutamic acid decarboxylase antibody-spectrum disorders (GAD-SDs) include a group of autoimmune neurological diseases associated with neuronal excitability, most noticeably stiff person syndrome. Immune modulators are the mainstay of treatment, but a significant number of patients remain refractory.<h4>Methods</h4>We present our single-center experience of eight cases of GAD-SD, two of which were refractory to immune modulatory treatments.<h4>Results</h4>Of the two cases that ...[more]
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Project description:Objective To describe clinical phenotypes and prognosis of neurological autoimmunity related to glutamic acid decarboxylase 65 (GAD65) antibodies in China. Method In this retrospective observational study from Peking Union Medical College Hospital, we identified patients with neurological disorders related to GAD65 antibodies (cell-based assay) from May 2015 to September 2021. Clinical manifestations, immunotherapy responsiveness, and outcomes were collected after obtaining informed consent from all patients. Results Fifty-five patients were included: 40 (72.73%) were women and initial neurological symptoms developed at 42(34-55) years of age. The median time to the nadir of the disease was 5 months (range from 1 day to 48 months). The clinical syndromes included limbic encephalitis (LE) or epilepsy (Ep) (n = 34, 61.82%), stiff-person syndromes (SPS) (n = 18, 32.73%), autoimmune cerebellar ataxia (ACA) (n = 11, 20%), and overlap syndrome in eight (14.55%) patients. Thirty-two (58.2%) patients had comorbidities of other autoimmune diseases, including Hashimoto thyroiditis (n = 17, 53.13%), T1DM (n = 11, 34.78%), vitiligo (n = 6, 18.75%), and others (n=5, 15.63%). Two (3.64%) patients had tumors, including thymoma and small cell lung cancer. Fifty-one (92.7%) patients received first-line immunotherapy (glucocorticoids and/or IV immunoglobulin), and 4 (7.3%) received second-line immunotherapy (rituximab). Long-term immunotherapy (mycophenolate mofetil) was administered to 23 (41.8%) patients. At the median time of 15 months (IQR 6–33.75 month, range 3–96 month) of follow-up, the patients' median modified Rankin Score (mRS) had declined from 2 to 1. Thirty-eight (70.4%) patients experienced clinical improvement (mRS declined ≥1), 47 (87%) had favorable clinical outcomes (mRS ≤2), and nine were symptom-free (16.7%). The sustained response to immunotherapy ranged from 7/15 (63.63%) in ACA patients and 22/34 (64.7%) in LE/Ep patients to 14/17 (82.35%) in SPS patients. Conclusions LE/Ep was the most common neurological phenotype of GAD65 antibody neurological autoimmunity in our cohort. Most patients had comorbidities of other autoimmune diseases, but underlying tumors were rare. Most patients responded to immunotherapy. However, the long-term prognosis varied among different clinical phenotypes.
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Project description:Stiff Person Syndrome (SPS) is an extremely rare neurological condition characterized by muscle stiffness and painful muscle spasms. The symptoms often progress slowly and can cause disability. Antibodies to glutamic acid decarboxylase (anti-GAD) have been reported in up to 80% of the classic type of SPS. Paraneoplastic syndrome comprises 5% of SPS cases. These patients present with different malignancies including lung, thymus, breast, colon, and lymph nodes. In this paper, we report a case of a 25-year-old Vietnamese female patient with SPS presenting with unusual clinical manifestations of sudden onset, rapidly progressive spinal, abdominal, and lower limb rigidity accompanied by painful spasms, autonomic disorders, and severe, multiple bone fractures. Serologic tests detected high-titer anti-GAD, combined with anti-SOX1 antibodies, suggesting paraneoplastic SPS. Intravenous immunoglobulin has been employed as the main treatment therapy, and the patient has had a complete remission.
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Project description:BackgroundTUBGCP2 variants are associated with the LIS spectrum disorders, but its pathogenesis remains unclear. To retrospectively analyze the clinical features and genetic information of patients having lissencephaly spectrum disorders associated with TUBGCP2 variants.MethodsClinical and genetic data of a patient diagnosed with TUBGCP2-related lissencephaly spectrum disorder at the Department of Pediatric Neurology, Shengjing Hospital, in March 2022 were collected. Furthermore, we reviewed previously reported literature on patients with the same gene variation.ResultsA 6-year-old female patient presented with microcephaly (head circumference: 46 cm, Z score: <-3), narrow forehead, thick eyebrows, bulbous nose, smooth philtrum, widened and separated teeth, speech and motor developmental delay, intellectual disability, and seizures. Brain magnetic resonance imaging showed pachygyria in the temporal, parietal, and occipital lobes. Gene testing identified hemizygous variation in TUBGCP2 (missense variants: c.178 C>T, c.538T>C, and maternal exon variant: 2-14 deletion). A literature search revealed seven patients with lissencephaly spectrum disorders associated with TUBGCP2 variants, including eight gene variation types. Moreover, the TUBGCP2 variants were found to cause lissencephaly spectrum diseases, with the main clinical manifestations being microcephaly, lissencephaly (including agyria, pachygyria, or subcortical band heterotopia), dysmorphic facial features (e.g., narrow forehead, thick eyebrows, bulbous nose, prominent ears, and widened and separated teeth), and developmental delay, with or without seizures.ConclusionOur study expands the genotype of this brain malformation disorder associated with TUBGCP2 variants by presenting the first case of TUBGCP2 variants causing lissencephaly spectrum disorders in China.
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Project description:Background In the current study, seizure semiology and potential predictive factors of seizure outcomes in glutamic acid decarboxylase antibody (GAD Ab)-associated neurological syndrome were investigated. Methods In this study, 32 Chinese patients with GAD Ab-associated neurological syndrome who presented with seizures at Peking Union Medical College Hospital from January 2017 to October 2022 were reviewed; 30 had a follow-up duration of more than 1 year. Results Among the 32 patients, 10 presented with epilepsy alone. Concomitant neurological syndromes were observed in 22 patients, including limbic encephalitis (n = 20), stiff-person syndrome (SPS, n = 1), and cerebellar ataxia (n = 1). Bilateral tonic–clonic seizures were observed in 21 patients (65.6%). Focal seizures occurred in 27 patients (84.4%); 17 had focal motor seizures and 18 focal non-motor seizures. Among 30 patients with long-term follow-up, 11 (36.7%) were seizure-free. Acute/subacute onset (p = 0.049) and comorbidity of limbic encephalitis with epilepsy (p = 0.023) led to better seizure outcomes. Patients with persistent epilepsy were more likely to have focal seizure (p = 0.003) and higher frequency of seizure (p = 0.001). Furthermore, these patients tended to have longer intervals from onset to immunomodulatory treatments. Early immunotherapy (within 6 months from onset) was administered in 81.8% of seizure-free patients but only in 42.1% of patients with persistent seizures. However, steroid and immunosuppressant duration did not differ in the two groups. Repeated serum GAD Ab tests during the follow-up showed no association with seizure outcomes. Conclusions The seizure manifestations are diverse and variable. Approximately one third of patients achieved seizure remission during long-term follow-up. The type and frequency of seizures may influence the seizure outcomes. Early immunotherapy, especially within 6 months, may lead to better seizure outcomes. Supplementary Information The online version contains supplementary material available at 10.1186/s12883-023-03182-x.
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Project description:Aspergillary rhinopharyngitis in an equine patient
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