Movement Disorders Associated with GABAA Receptor Encephalitis: A Video Case Report.
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ABSTRACT:
SUBMITTER: Vacchiano V
PROVIDER: S-EPMC7396850 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo report the clinical features, comorbidities, receptor subunit targets, and outcome in patients with anti-GABAA receptor (GABAAR) encephalitis.MethodsClinical study of 26 patients, including 17 new (April 2013-January 2016) and 9 previously reported patients. Antibodies to α1, β3, and γ2 subunits of the GABAAR were determined using reported techniques.ResultsPatients' median age was 40.5 years (interquartile range 48.5 [13.75-62.35] years; the youngest 2.5 months old; 13 female). Symptoms included seizures (88%), alteration of cognition (67%), behavior (46%), consciousness (42%), or abnormal movements (35%). Comorbidities were identified in 11 (42%) patients, including 7 tumors (mostly thymomas), 2 herpesvirus encephalitis (herpes simplex virus 1, human herpesvirus 6; coexisting with NMDAR antibodies), and 2 myasthenia without thymoma. Brain MRI was abnormal in 23 (88%) patients, showing in 20 (77%) multifocal, asynchronous, cortical-subcortical T2/fluid-attenuated inversion recovery abnormalities predominantly involving temporal (95%) and frontal (65%) lobes, but also basal ganglia and other regions. Immunologic or tumor therapy resulted in substantial improvement in 18/21 (86%) assessable patients; the other 3 (14%) died (2 status epilepticus, 1 sepsis). Compared with adults, children were more likely to have generalized seizures (p = 0.007) and movement disorders (p = 0.01) and less likely to have a tumor (p = 0.01). The main epitope targets were in the α1/β3 subunits of the GABAAR.ConclusionsAnti-GABAAR encephalitis is characterized by frequent seizures and distinctive multifocal cortical-subcortical MRI abnormalities that provide an important clue to the diagnosis. The frequency of symptoms and comorbidities differ between children (more viral-related) and adults (more tumor-related). The disorder is severe but most patients respond to treatment.
| S-EPMC5384834 | biostudies-literature
Project description:BackgroundIn 2010 the spectrum of known antigens in autoimmune encephalitis has been expanded by GABAB receptors. Until now over 80 patients with GABAB receptor encephalitis have been described. We report the occurrence of GABAB receptor antibodies in a patient with clinically diagnosed amyotrophic lateral sclerosis (ALS). GABAB receptor antibodies have not been described previously in an ALS patient.Case presentationA 75-year-old female patient presented with cerebellar ataxia, bulbar palsy and cognitive impairment. In the later course of disease signs for affection of the second motor neuron evolved and she was diagnosed with ALS. A post-mortem analysis of cerebrospinal fluid revealed high titers of GABAB receptor antibodies.ConclusionsThis case provides an idea of the natural course of GABAB receptor encephalitis and demonstrates that antibody-mediated autoimmunity could be one of several pathways leading to the ALS phenotype. Furthermore this unique case stimulates the question whether neuronal antibodies might be more common in ALS than previously suspected.
| S-EPMC6416932 | biostudies-literature
Project description: Not available
| S-EPMC3806918 | biostudies-literature
Project description:Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABAA-R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised. Here we identified a strongly expanded B cell clone in the cerebrospinal fluid of a patient with GABAA-R encephalitis. We expressed the antibody produced by it and showed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry that it recognizes the GABAA-R. Patch-clamp recordings revealed that it tones down inhibitory synaptic transmission and causes increased excitability of hippocampal CA1 pyramidal neurons. Thus, the antibody likely contributed to clinical disease symptoms. Hybridization to a protein array revealed the cross-reactive protein LIM-domain-only protein 5 (LMO5), which is related to cell-cycle regulation and tumor growth. We confirmed LMO5 recognition by immunoprecipitation and ELISA and showed that cerebrospinal fluid samples from two other patients with GABAA-R encephalitis also recognized LMO5. This suggests that cross-reactivity between GABAA-R and LMO5 is frequent in GABAA-R encephalitis and supports the hypothesis of a paraneoplastic etiology.
| S-EPMC7936355 | biostudies-literature
Project description:AimsAMPA receptor (AMPAR) and CRMP5 antibodies are relatively uncommon in limbic encephalitis, and patients with both antibodies are rare. We recently treated such a patient, but the patient died after active treatment. To further understand this disease, we conducted a case report and literature review.DiscussionsTo date, five encephalitis patients, including our patient, have been found to be positive for AMPAR and CRMP5 antibodies. The male-to-female ratio of the reported cases is 4:1, and the age range is 26 and 62 years old. All five patients presented with various neuropsychiatric symptoms, including insomnia, abnormal behavior, seizures, extrapyramidal symptoms, and autonomic dysfunction. Four patients had tumors (three invasive thymomas and one suspected lymphoma), and three cases died within a short period of time. No tumor was detected in one of the patients during the follow-up period; however, after active treatment, the outcome was poor, and the patient developed cachexia. One patient had good response to immunotherapy and tumor therapy and successfully returned to work.ConclusionsThe prognosis of encephalitis associated with AMPAR and CRMP5 antibodies is worse than that of the encephalitis associated with AMPAR antibodies alone. The most likely cause is that this encephalitis is more likely to be accompanied by malignant tumors, leading to a poor prognosis. In addition, it may also be due to some synergistic mechanisms between the two antibodies. Further studies aimed at the prognosis of this type of encephalitis are warranted.
| S-EPMC7066334 | biostudies-literature
Project description:Background GNAO1 variants have been found to be associated with epileptic encephalopathies, developmental delays (DDs), and movement disorders (MDs). Therapies for patients with GNAO1 variants vary. However, treatments for GNAO1-related diseases are still in their infancy. Previous reports suggest that few pharmacological treatments are effective for patients with GNAO1 variant-related MDs. Deep brain stimulation (DBS) treatment appears to be effective, however surgical procedures and equipment failures pose risks to the patients. Effectiveness for oxcarbazepine (OXC) in GNAO1 variant-related MDs is first reported in our study, and it expand the effective drugs for MD treatment. Case Description We report the case of a 5-year-old male patient with a MD, who suffered from hypotonia and refractory choreoathetosis. The patient was found to have a DD and an intellectual disability. A de-novo variant of the GNAO1 gene (NM_138736: exom6: c.709G>A [p. Glu237Lys]) was identified by whole exome sequencing (WES) when he was 8 months old. The patient visited our hospital at the age of 4 years and 3 months because of fever and recurrent convulsions. Electroencephalogram (EEG) results show abnormal spikes, and magnetic resonance imaging (MRI) showed the enlargement of the lateral ventricles. The administration of tiapride hydrochloride, phenobarbital, midazolam, and hormones had no effect. OXC treatment was then initiated. No MD behaviors, such as rigidity and twisting of the limbs and trunk, or chorea, were observed after 10 days OXC treatment. Eventually, incremental doses of OXC were effective, and our patient achieved good control of his MD. Conclusions We are the first to demonstrate the role of OXC in alleviating MDs associated with GNAO1 mutations. This report provides a novel possibility for the clinical treatment of this rare disease. To manage MDs associated with GNAO1 mutations, we recommend that OXC treatment be attempted before invasive surgical therapy.
| S-EPMC9561508 | biostudies-literature
Project description:BackgroundCentral nervous system diseases are common triggers of Takotsubo syndrome. We herein report a rare case of Takotsubo syndrome associated with autoimmune limbic encephalitis.Case presentationA 68-year-old Japanese woman presented to our emergency room with disturbed consciousness. At admission, she showed hypoxemia. Left ventriculography showed akinesia in the middle part of the left ventricle and hyperkinesia in the apical and basal parts of the left ventricle, and the diagnosis of midventricular Takotsubo syndrome was established. However, after an improvement in disturbed consciousness and Takotsubo syndrome symptoms, her brother noticed something wrong with her behavior during his visit to the hospital. Subsequently, we consulted the neurology department 1 week after admission. Her brother revealed a history of abnormal behavior by the patient (such as mistaken entry in the wrong apartment in her building or in another person's car) a few days prior to the onset of disturbed consciousness, suggesting disorientation of place. Brain magnetic resonance imaging showed an increased signal in the medial aspect of the temporal lobes, which was most clearly observed on the fluid-attenuated inversion recovery sequence; additionally, a cerebrospinal fluid analysis revealed mild lymphocytic pleocytosis. Finally, we established a diagnosis of midventricular Takotsubo syndrome associated with autoimmune limbic encephalitis.ConclusionsIt is presumed that the dysfunction of limbic system due to autonomic limbic encephalopathy is associated with exaggerated sympathetic stimulation. This likely resulted in Takotsubo syndrome in our patient.
| S-EPMC7879610 | biostudies-literature
Project description:Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor control deficits, which is associated with the loss of striatal dopaminergic neurons from the substantia nigra. In parallel to dopaminergic denervation, there is an increase of acetylcholine within the striatum, resulting in a striatal dopaminergic-cholinergic neurotransmission imbalance. Currently, available PD pharmacotherapy (e.g., prodopaminergic drugs) does not reinstate the altered dopaminergic-cholinergic balance. In addition, it can eventually elicit cholinergic-related adverse effects. Here, we investigated the interplay between dopaminergic and cholinergic systems by assessing the physical and functional interaction of dopamine D2 and muscarinic acetylcholine M1 receptors (D2R and M1R, respectively), both expressed at striatopallidal medium spiny neurons. First, we provided evidence for the existence of D2R-M1R complexes via biochemical (i.e., co-immunoprecipitation) and biophysical (i.e., BRET1 and NanoBiT®) assays, performed in transiently transfected HEK293T cells. Subsequently, a D2R-M1R co-distribution in the mouse striatum was observed through double-immunofluorescence staining and AlphaLISA® immunoassay. Finally, we evaluated the functional interplay between both receptors via behavioral studies, by implementing the classical acute reserpine pharmacological animal model of experimental parkinsonism. Reserpinized mice were administered with a D2R-selective agonist (sumanirole) and/or an M1R-selective antagonist (VU0255035), and alterations in PD-related behavioral tasks (i.e., locomotor activity) were evaluated. Importantly, VU0255035 (10 mg/kg) potentiated the antiparkinsonian-like effects (i.e., increased locomotor activity and decreased catalepsy) of an ineffective sumanirole dose (3 mg/kg). Altogether, our data suggest the existence of putative striatal D2R/M1R heteromers, which might be a relevant target to manage PD motor impairments with fewer adverse effects.
| S-EPMC7083216 | biostudies-literature
Project description:Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is a relatively rare anti-neuronal surface antigen autoimmune encephalitis (LE). We described a case of a 47-year-old Chinese man having anti-AMPA receptor limbic encephalitis initially presented with cognitive decline, undetectable antibodies, and normal imaging findings in magnetic resonance image (MRI) and then developed into typical autoimmune limbic encephalitis a few months later with a course of multiple relapses. In addition, we found progressive brain atrophy in our case, which was a rare presentation of LE. This report also summarized the characteristics of nine reported cases of anti-AMPA receptor limbic encephalitis with relapse up to date. This case highlighted that autoimmune limbic encephalitis is an important differential diagnosis for patients with typical symptoms even when the MRI and antibodies are normal, and more attention should be paid to the relapse of anti-AMPA receptor encephalitis.
| S-EPMC8690251 | biostudies-literature
Project description:ObjectiveMovement disorders (MDs) are common in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis but are poorly studied. This study aimed to investigate the clinical characteristics of MDs and the clinical differences between patients with and without MDs in anti-NMDAR encephalitis.MethodsA retrospective study was conducted on patients with anti-NMDAR encephalitis who were first diagnosed and treated in the First People's Hospital of Yunnan Province from January 2017 to September 2022. According to the presence or absence of MDs, all patients were divided into two groups, and the clinical manifestations, auxiliary examinations, and prognosis of the two groups were compared. Patients in the MDs group were further subgrouped by different ages (<12 years, 12-17 years, and ≥ 18 years) and genders, and the prevalence of each MD was compared in different age and gender groups.Results(1) In our study there were 64 patients, of whom 76.6% (49/64) presented with MDs; the median age of onset in patients with MDs was 21 (15,35) years and 65.3% (32/49) were female. The three most common MDs were orofacial dyskinesia (OFLD) (67.3%), dystonia (55.1%), and stereotypies (34.7%). Patients <12 years were more likely to experience chorea than patients in other age groups (p = 0.003). (2) Compared with the non-MDs group, patients in the MDs group showed higher rates of prodromal manifestations, autonomic dysfunction, consciousness disorders, as well as pulmonary infection and gastrointestinal dysfunction (all p < 0.05). Peripheral blood neutrophil to lymphocyte ratio (NLR) (p = 0.014), the proportion of cerebrospinal fluid (CSF) NMDAR antibody titers ≥1:32 (p = 0.047), ICU admission rate (p = 0.04), length of stay (p = 0.007), maximum mRS score in the course of disease (p = 0.001) and mRS score at discharge (p = 0.006) in the MDs group were significantly higher than the non-MDs group.ConclusionMDs associated with anti-NMDAR encephalitis were predominantly hyperkinetic. Chorea occurred more commonly in patients aged <12 years. Patients with MDs were prone to autonomic dysfunction, consciousness disorders, pulmonary infection, and gastrointestinal dysfunction; they had more intense inflammation, more severe disease, and a poorer short-term prognosis.
| S-EPMC10941647 | biostudies-literature