Coexistence of anti-SOX1 and anti-GABAB receptor antibodies with paraneoplastic limbic encephalitis presenting with seizures and memory impairment in small cell lung cancer: A case report
7
Citation
31
Reference
10
Related Paper
Citation Trend
Abstract:
Purpose Paraneoplastic neurological syndromes associated with autoantibodies are rare diseases that cause abnormal manifestations of the nervous system. Early diagnosis of paraneoplastic neurological syndromes paves the way for prompt and efficient therapy. Case report we reported a 56-year-old man presenting with seizures and rapidly progressive cognitive impairment diagnosed as paraneoplastic limbic encephalitis (PLE) with anti-SRY-like high-mobility group box-1 (SOX-1) and anti-γ-aminobutyric acid B (GABAB) receptor antibodies and finally confirmed by biopsy as small cell lung cancer (SCLC). At the first admission, brain magnetic resonance imaging (MRI) showed no abnormal signal in bilateral hippocampal regions and no abnormal enhancement of enhanced scan. The serum anti-GABAB receptor antibody was 1:100 and was diagnosed as autoimmune encephalitis (AE). The computed tomography (CT) scans of the chest showed no obvious tumor signs for the first time. Although positron emission tomography-computed tomography (PET-CT) revealed hypermetabolism in the para mid-esophageal, the patient and his family declined to undertake a biopsy. The patient improved after receiving immunoglobulin, antiepileptic therapy, and intravenous methylprednisolone (IVMP) pulse treatment. However, after 4 months, the symptoms reappeared. Brain MRI revealed abnormal signals in the hippocampal regions. Reexamination of the cerebral fluid revealed anti-GABAB receptor and anti-SOX-1 antibodies, which contributed to the diagnosis of PLE. SCLC was found in a para mid-esophageal pathological biopsy. Antiepileptic medications and immunoglobulin were used to treat the patient, and the symptoms were under control. Conclusion Our findings increase the awareness that patients with limbic encephalitis with cognitive dysfunction and epileptic seizures should be enhanced to detect latent malignancy. Our case also highlights the importance of anti-SOX1 antibodies in the detection of underlying neoplasm, particularly SCLC. Our findings raise awareness of the cognitive impairment seen by patients with limbic encephalitis.Keywords:
Limbic Encephalitis
Autoimmune encephalitis
Autoimmune encephalitis can be classified into antibody-defined subtypes, which can manifest with immunotherapy-responsive movement disorders sometimes mimicking non-inflammatory aetiologies. In the elderly, anti-LGI1 and contactin associated protein like 2 (CASPR2) antibody-associated diseases compose a relevant fraction of autoimmune encephalitis. Patients with LGI1 autoantibodies are known to present with limbic encephalitis and additionally faciobrachial dystonic seizures may occur. However, the clinical spectrum of CASPR2 autoantibody-associated disorders is more diverse including limbic encephalitis, Morvan's syndrome, peripheral nerve hyperexcitability syndrome, ataxia, pain and sleep disorders. Reports on unusual, sometimes isolated and immunotherapy-responsive movement disorders in CASPR2 autoantibody-associated syndromes have caused substantial concern regarding necessity of autoantibody testing in patients with movement disorders. Therefore, we aimed to systematically assess their prevalence and manifestation in patients with CASPR2 autoimmunity. This international, retrospective cohort study included patients with CASPR2 autoimmunity from participating expert centres in Europe. Patients with ataxia and/or movement disorders were analysed in detail using questionnaires and video recordings. We recruited a comparator group with anti-LGI1 encephalitis from the GENERATE network. Characteristics were compared according to serostatus. We identified 164 patients with CASPR2 autoantibodies. Of these, 149 (90.8%) had only CASPR2 and 15 (9.1%) both CASPR2 and LGI1 autoantibodies. Compared to 105 patients with LGI1 encephalitis, patients with CASPR2 autoantibodies more often had movement disorders and/or ataxia (35.6 versus 3.8%; P < 0.001). This was evident in all subgroups: ataxia 22.6 versus 0.0%, myoclonus 14.6 versus 0.0%, tremor 11.0 versus 1.9%, or combinations thereof 9.8 versus 0.0% (all P < 0.001). The small group of patients double-positive for LGI1/CASPR2 autoantibodies (15/164) significantly more frequently had myoclonus, tremor, 'mixed movement disorders', Morvan's syndrome and underlying tumours. We observed distinct movement disorders in CASPR2 autoimmunity (14.6%): episodic ataxia (6.7%), paroxysmal orthostatic segmental myoclonus of the legs (3.7%) and continuous segmental spinal myoclonus (4.3%). These occurred together with further associated symptoms or signs suggestive of CASPR2 autoimmunity. However, 2/164 patients (1.2%) had isolated segmental spinal myoclonus. Movement disorders and ataxia are highly prevalent in CASPR2 autoimmunity. Paroxysmal orthostatic segmental myoclonus of the legs is a novel albeit rare manifestation. Further distinct movement disorders include isolated and combined segmental spinal myoclonus and autoimmune episodic ataxia.
Autoimmune encephalitis
Limbic Encephalitis
Movement Disorders
Neuromyotonia
Cite
Citations (24)
The coexistence of leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) autoantibodies in the same individual is surprisingly often observed. We herein report the first case of LGI1 encephalitis followed by Isaacs syndrome in which LGI1 and CASPR2 antibodies in the serum and cerebrospinal fluid (CSF) were measured during the entire disease course. After the resolution of limbic encephalitis, LGI1 antibodies disappeared from the CSF simultaneously with the appearance of CASPR2 antibodies in the serum. The alternating presence of these pathogenic autoantibodies along with the clinical and phenotypic alternations suggested that LGI1 encephalitis was associated with CASPR2 autoantibody production in the peripheral tissue, leading to CASPR2-associated Isaacs syndrome.
Limbic Encephalitis
Autoimmune encephalitis
Cite
Citations (0)
Autoimmune encephalitis (AE) is a kind of newly discovered autoimmune disease of the central nervous system. The cause of autoimmune encephalitis is complex and symptoms are lacking in specificity. There are many difficulties in diagnosis of AE. The clinical diagnosis of AE should be combined with its clinical characteristics, the detection of AE-related autoantibodies and laboratory-related tests, electroencephalogram, head imaging, et al. AE-related autoantibody detection is more helpful in the diagnosis, some of the autoantibodies also have a strong hint of potential tumor in the body, and can help to determine the treatment and prognosis.(Chin J Lab Med, 2017, 40: 928-932)
Key words:
Encephalitis; Hashimoto disease; Autoantibodies; Clinical laboratory techniques
Autoimmune encephalitis
Limbic Encephalitis
Clinical Diagnosis
Cite
Citations (0)
The role of autoimmune responses against central nervous system (CNS) antigens in encephalitis presenting with non-classified neurologic or psychiatric symptoms has been appreciated in the past decade. Paraneoplastic limbic encephalitis has a poor prognosis and is most commonly associated with lung, ovarium, and testicular neoplasms, leading to immune reactions against intracellular antigens (anti-Hu/ANNA1, anti-Ri/ANNA2, anti-CV2/CRMP5 and anti-Ma2/Ta). In contrast, the recently described autoimmune encephalitis subtypes present with a broad spectrum of symptoms, respond to autoimmune therapies well and usually associate with autoantibodies against neuronal cell surface receptors (NMDAR, GABABR, AMPAR) or synaptic proteins (LGI1, CASPR2).Our aim is to bring to awareness the increasing number of autoimmune encephalitis patients requiring neurologic, psychiatric and intensive care and to emphasize the significance of detecting various autoantibodies in diagnosing patients.In the past 6 years, our laboratory received 836 autoimmune encephalitis diagnostic test requests from a total of 717 patients. Serum and cerebrospinal fluid (CSF) samples were analysed with indirect immunofluorescence using a BIOCHIP consisting of cell lines transfected with 6 different receptor proteins.IgG autoantibodies against receptor proteins were present in 7.5% of patients. The frequency of positive samples was the following: NMDAR > LGI1 > GABABR > CASPR2.Detecting autoantibodies facilitates the diagnosis of autoimmune encephalitis in an early stage. Patients diagnosed early can be effectively treated with plasmapheresis and immunosuppressive drugs. The efficiency of therapies can be monitored by autoantibody detection. Therefore, the diagnostic immune laboratory plays an important role in proper diagnosis and in the prevention of rapidly progressing symptoms. Orv Hetil. 2018; 159(3): 107-112.
Autoimmune encephalitis
Limbic Encephalitis
Biochip
Cite
Citations (0)
Summary Autoantibodies to surface proteins that influence neuronal excitability are increasingly found in different forms of epilepsy or encephalitis in adults, and are also beginning to be identified in children. The conditions are often refractory to traditional antiepileptic drugs. Detection of these antibodies can help to identify forms of epilepsy that may respond to immunotherapies.
Cite
Citations (34)
Movement disorders are common manifestations in autoimmune-mediated encephalitis. This group of diseases is suspected to be triggered by infection or neoplasm. Certain phenotypes correlate with specific autoantibody-related neurological disorders, such as orofacial-lingual dyskinesia with N-methyl-D-aspartate receptor encephalitis and faciobrachial dystonic seizures with leucine-rich glioma-inactivated protein 1 encephalitis. Early diagnosis and treatment, especially for autoantibodies targeting neuronal surface antigens, can improve prognosis. In contrast, the presence of autoantibodies against intracellular neuronal agents warrants screening for underlying malignancy. However, early clinical diagnosis is challenging because these diseases can be misdiagnosed. In this article, we review the distinctive clinical phenotypes, magnetic resonance imaging findings, and current treatment options for autoimmune-mediated encephalitis.
Autoimmune encephalitis
Movement Disorders
Limbic Encephalitis
Cite
Citations (2)
Objective: Outline the clinical course of a patient with multiple autoantibody-related paraneoplastic limbic encephalitis with complete neurologic recovery after treatment. Background: AMPA-Rc, GABA-B-Rc, and CRMP-5 antibodies have been associated with paraneoplastic limbic encephalitis. The presence of concurrent cell-surface and onconeuronal antibodies is associated with poor prognosis. To our knowledge, no reports describe a similar profile of autoantibodies with a favorable outcome as our patient. Design/Methods: Case Report Results: A 39-year-old woman presented with two weeks of behavioral change and amnesia progressing to coma requiring intubation. A mediastinal mass was found on imaging with pathology consistent with thymoma. Further testing showed multiple positive serum autoantibodies against AMPA-Rc (CBA positive;IF titer 1:7680), GABA-B-Rc (CBA positive; 1:7680), CRMP-5 (Western blot Positive), AchR binding (2.11nmol/L), AchR modulating Ab (93%), and N-Type Calcium (0.05nmol/L). CSF revealed anti-AMPA-Rc antibodies. Tumor location delayed surgery and she underwent emergent treatment with PLEX in tandem with neoadjuvant chemotherapy. Her mental status improved and she was discharged home and subsequently underwent thymoma resection and post-operative radiotherapy due to positive resection margins. At 1 year follow-up she has had a continued favorable outcome with return to premorbid baseline. Conclusions: The case presented is unique from previously described cases of autoimmune encephalitis due to it’s impressive autoantibody profile and complete recovery after treatment. It is unclear if the encephalitis was driven from a single autoantibody or an additive effect of multiple autoantibodies. Although, it is possible that the AMPA-Rc antibody was the main driving force of her encephalitis given the presence of high serum titer and presence in spinal fluid. While definitive treatment with surgical resection was delayed, she responded dramatically to plasma exchange which allowed her to be discharged home to complete her therapy. This is notable due to the generally poor prognosis associated with multiple autoantibody-related limbic encephalitis. Disclosure: Dr. Shoemaker has nothing to disclose. Dr. Newsome has nothing to disclose.
Limbic Encephalitis
Limbic system
Autoimmune encephalitis
Cite
Citations (0)
Autoimmune encephalitis is a group of encephalitis syndromes that cause altered mentality, memory decline, or seizures in association with the presence of serum and cerebrospinal fluid (CSF) autoantibodies (auto-Abs).An early diagnosis enables early treatments.The detection of auto-Abs is a confirmatory diagnosis.Tissue-based assay, cell-based immunoassay, and immunoblotting are used to detect various autoantibodies.The CSF test for the presence of antibodies is important because it is more sensitive and reflects disease activity in many autoimmune encephalitis, although antibody tests can be negative even in the presence of autoimmune encephalitis.EEG is often abnormal, but nonspecific.A unilateral or bilateral medial temporal T2 high signal is a common finding in MRI.Fludeoxyglucose-positron emission tomography is sometimes useful for diagnosis in patients with normal MRI.(2016;6:45-52)
Autoimmune encephalitis
Limbic Encephalitis
Cite
Citations (117)
Cite
Citations (11)
Abstract Our review aims to delineate the psychiatric spectrum of autoantibody-associated autoimmune encephalitis over time through its discoveries of antibodies. We searched in PubMed for appropriate articles depicting the first appearance and spectrum of psychiatric symptomatology in autoantibody-positive encephalitis for this narrative review. Memory impairment was first associated with autoantibodies against intracellular antigens such as anti-HuD antibodies in 1993. 8 years later, autoantibodies against cell membrane surface antigens such as voltage-gated potassium channels were described in conjunction with memory dysfunction. The spectrum of psychiatric syndromes was amplified between 1990 and 2020 to include disorientation, behavior, cognitive dysfunction, obsessive compulsive behavior and suicidality in encephalitis patients occurring together mainly with antibodies against surface antigens, less so against intracellular antigens. In general, we found no specific psychiatric symptoms underlying specific autoantibody-associated encephalitis. As fundamental data on this issue have not been systemically assessed to date, we cannot know whether our specific findings would remain from systematic studies, i.e., on the association between cerebrospinal fluid N-methyl-D-aspartate receptor antibodies in catatonia. The psychiatric symptomatology overlaps between psychiatric domains and occurs frequently in antibody-positive encephalitis. No specific psychiatric symptoms imply an underlying, specifically autoantibody-associated encephalitis. The psychiatric phenotypology associated with antibody-positive encephalitis has evolved tremendously recently, and this new evidence reveals its relevance for future diagnostic and treatment aspects of autoimmune encephalitis patients.
Autoimmune encephalitis
Catatonia
Limbic Encephalitis
Cite
Citations (28)