Faciobrachial Dystonic Seizures Research Articles

Autoimmune-associated seizure disorders.

With the discovery of an expanding number of neural autoantibodies, autoimmune etiologies of seizures have been increasingly recognized. Clinical phenotypes have been identified in association with specific underlying antibodies, allowing an earlier diagnosis. These phenotypes include faciobrachial dystonic seizures with LGI1 encephalitis, neuropsychiatric presentations associated with movement disorders and seizures in NMDA-receptor encephalitis, and chronic temporal lobe epilepsy in GAD65 neurologic autoimmunity. Prompt recognition of these disorders is important, as some of them are highly responsive to immunotherapy. The response to immunotherapy is highest in patients with encephalitis secondary to antibodies targeting cell surface synaptic antigens. However, the response is less effective in conditions involving antibodies binding intracellular antigens or in Rasmussen syndrome, which are predominantly mediated by cytotoxic T-cell processes that are associated with irreversible cellular destruction. Autoimmune encephalitides also may have a paraneoplastic etiology, further emphasizing the importance of recognizing these disorders. Finally, autoimmune processes and responses to novel immunotherapies have been reported in new-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES), warranting their inclusion in any current review of autoimmune-associated seizure disorders.

Two Cases of Pediatric Leucine-Rich Glioma-Inactivated Protein-1 Encephalitis: Clinical Course, Challenges, and Implications

BackgroundLeucine-rich glioma-inactivated protein 1 (LGI-1) encephalitis is a rare form of autoimmune limbic encephalitis. Although relatively well documented in adults, pediatric cases are rare and remain poorly understood. MethodsWe reviewed two pediatric cases of LGI-1 encephalitis from a single tertiary care facility retrospectively. The detailed analysis included assessment of the initial presentation, clinical progression, diagnostic challenges, treatments, and outcome. To contextualize the differences between pediatric and adult manifestations of disease, we compared these findings with existing literature. ResultsBoth cases illustrate the diagnostic challenges faced at initial presentation due to the rarity of this diagnosis in children and the absence of characteristic faciobrachial dystonic seizures, which is common in adults. The constellation of neuropsychiatric symptoms and refractory focal seizures led to a high clinical suspicion for autoimmune encephalitis, therefore, both cases were treated empirically with intravenous methylprednisolone. The diagnosis in both cases was confirmed with positive serum antibody testing, reinforcing that LGI-1 antibodies are more sensitive in the serum rather than the cerebrospinal fluid (CSF). Seizure control and improvement in cognitive symptoms was achieved through a combination of immunotherapy and antiseizure medications. ConclusionsThis case series underscores the significance of considering LGI-1 encephalitis in the differential diagnosis of pediatric patients exhibiting unexplained neuropsychiatric symptoms and focal seizures and emphasizes the importance of performing both serum and CSF antibody testing. It is necessary to conduct further research to identify the full range of pediatric presentations and to determine the optimal treatment protocol.

Peripherally-derived LGI1-reactive monoclonal antibodies cause epileptic seizures in vivo.

One striking clinical hallmark in patients with autoantibodies to leucine-rich glioma inactivated 1 (LGI1) is the very frequent focal seizure semiologies, including faciobrachial dystonic seizures (FBDS), in addition to the amnesia. Polyclonal serum IgGs have successfully modelled the cognitive changes in vivo but not seizures. Hence, it remains unclear whether LGI1-autoantibodies are sufficient to cause seizures. We tested this with the molecularly precise monoclonal antibodies directed against LGI1 (LGI1-mAbs), derived from patient circulating B cells. These were directed towards both major domains of LGI1, LRR and EPTP and infused intracerebroventricularly over 7 days into juvenile male Wistar rats using osmotic pumps. Continuous wireless EEG was recorded from a depth electrode placed in hippocampal CA3 plus behavioural tests for memory and hyperexcitability were performed. Following infusion completion (Day 9), post-mortem brain slices were studied for antibody binding and effects on Kv1.1. The LGI1-mAbs bound most strongly in the hippocampal CA3 region and induced a significant reduction in Kv1.1 cluster number in this subfield. By comparison to control-Ab injected rats video-EEG analysis over 9 days revealed convulsive and non-convulsive seizure activity in rats infused with LGI1-mAbs, with a significant number of ictal events. Memory was not impaired in the novel object recognition test. Peripherally-derived human LGI1-mAbs infused into rodent CSF provide strong evidence of direct in vivo epileptogenesis with molecular correlations. These findings fulfill criteria for LGI1-antibodies in seizure causation.

Anti-LGI1 autoimmune encephalitis: insights from three cases with serial PET imaging

BackgroundAutoimmune encephalitis (AE) can be a disabling condition, but it is manageable when identified in its early phases. Multiple diagnostic modalities can aid the diagnosis and delineation of areas of involvement in the brain, which is essential in correlating the symptoms to their pathology.Case presentationThis case series focuses on three cases of anti-LGI1 encephalitis in their 3rd and 5th decades, each displaying facio-brachial dystonic seizures (FBDS) and varying symptoms, such as behavioural changes and hyperhidrosis. Their MRI brains were not conclusive, but when the patients underwent a PET scan, all three of them showed involvement of the Basal Ganglia, which reversed along with clinical improvement after standard treatment for AE.ConclusionsAE can be a morbid condition for a long time, but some factors that might predispose to better patient outcomes might be early diagnosis and treatment. A PET scan is a modality that might help pick up functional changes before structural changes set in, and so should be considered in the diagnostic workup. Patterns of involvement of brain areas in Anti LGI1 AE need delineation, and basal ganglia seems to be a consistent region of involvement.

Neurological, psychiatric, and sleep investigations after treatment of anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis in Spain: a prospective cohort study

Anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis is an autoimmune disorder that can be treated with immunotherapy, but the symptoms that remain after treatment have not been well described. We aimed to characterise the clinical features of patients with anti-LGI1 encephalitis for 1 year starting within the first year after initial immunotherapy. For this prospective cohort study, we recruited patients with anti-LGI1 encephalitis as soon as possible after they had received conventional immunotherapy for initial symptoms; patients were recruited from 21 hospitals in Spain. Patients were excluded if they had an interval of more than 1 year since initial immunotherapy, had pre-existing neurodegenerative or psychiatric disorders, or were unable to travel to Hospital Clínic de Barcelona (Barcelona, Spain). Patients visited Hospital Clínic de Barcelona on three occasions-the first at study entry (visit 1), the second 6 months later (visit 2), and the third 12 months after the initial visit (visit 3). They underwent neuropsychiatric and videopolysomnography assessments at each visit. Healthy participants who were matched for age and sex and recruited from Hospital Clínic de Barcelona underwent the same investigations at study entry and at 12 months. Cross-sectional comparisons of clinical features between groups were done with conditional logistic regression, and binary logistic regression was used to assess associations between cognitive outcomes at 12 months and clinical features before initial immunotherapy and at study entry. Between May 1, 2019, and Sept 30, 2022, 42 participants agreed to be included in this study. 24 (57%) participants had anti-LGI1 encephalitis (mean age 63 years [SD 12]; 13 [54%] were female and 11 [46%] were male) and 18 (43%) were healthy individuals (mean age 62 years [10]; 11 [61%] were female and seven [39%] were male). At visit 1 (median 88 days [IQR 67-155] from initiation of immunotherapy), all 24 patients had one or more symptoms; 20 (83%) patients had cognitive deficits, 20 (83%) had psychiatric symptoms, 14 (58%) had insomnia, 12 (50%) had rapid eye movement (REM)-sleep behaviour disorder, nine (38%) had faciobrachial dystonic seizures, and seven (29%) had focal onset seizures. Faciobrachial dystonic seizures were unnoticed in four (17%) of 24 patients and focal onset seizures were unnoticed in five (21%) patients. At visit 1, videopolysomnography showed that 19 (79%) patients, but no healthy participants, had disrupted sleep structure (p=0·013); 15 (63%) patients and four (22%) healthy participants had excessive fragmentary myoclonus (p=0·039), and nine (38%) patients, but no healthy participants, had myokymic discharges (p=0·0051). These clinical and videopolysomnographic features led to additional immunotherapy in 15 (63%) of 24 patients, which resulted in improvement of these features in all 15 individuals. However, at visit 3, 13 (65%) of 20 patients continued to have cognitive deficits. Persistent cognitive deficits at visit 3 were associated with no use of rituximab before visit 1 (odds ratio [OR] 4·0, 95% CI 1·5-10·7; p=0·0015), REM sleep without atonia at visit 1 (2·2, 1·2-4·2; p=0·043), and presence of LGI1 antibodies in serum at visit 1 (11·0, 1·1-106·4; p=0·038). Unsuspected but ongoing clinical and videopolysomnography alterations are common in patients with anti-LGI1 encephalitis during the first year or more after initial immunotherapy. Recognising these alterations is important as they are treatable, can be used as outcome measures in clinical trials, and might influence cognitive outcome. Fundació La Caixa.

Leucine-Rich Glioma-Inactivated 1 (LGI1) Protein Stimulates Proliferation and IL-10 Production in Peripheral Blood Mononuclear Cells of Patients with LGI1 Antibody-Mediated Autoimmune Encephalitis In Vitro.

Limbic encephalitis (LE) due to anti-leucine-rich glioma-inactivated 1 (LGI1) antibodies is an autoimmune disease characterized by distinct clinical features unique to LGI1 LE, such as faciobrachial dystonic seizures. However, it is unclear whether an additional disease-related LGI1 antigen-specific T cell response is involved in the pathogenesis of this disease. To address this question, we studied the effect of recombinant LGI1 on the proliferation and effector-specific cytokine production (IFN-γ, IL-5, IL-10, and IL-17) of peripheral blood mononuclear cells (PBMCs) from patients with LGI1 LE and healthy controls. We observed that recombinant LGI1 stimulated the proliferation of PBMCs from patients with LGI1 LE, but not from healthy controls. Cytokine measurement of cell culture supernatants from PBMCs incubated with recombinant LGI1 revealed a highly significant increase in IL-10 release in PBMCs from patients with LGI1 LE in comparison with healthy controls. These results suggest that LGI1-mediated stimulation of PBMCs from patients with LGI1 LE leads to the establishment of an IL-10-dominated immunosuppressive cytokine milieu, which may inhibit Th1 differentiation and support B cell proliferation, IgG production, and IgG subclass switching.

Anti-leucine-rich Glioma-inactivated 1 Protein-antibody Positive Encephalitis with Extensive Unilateral Cerebral Cortex and White Matter Lesions.

Encephalitis caused by antibodies targeting the leucine-rich glioma-inactivated 1 protein receptor, which belongs to the anti-voltage-gated potassium channel receptor complex, is characterized by hyponatremia, progressive cognitive impairment, seizures, and psychiatric disorders. The patient initially presented with faciobrachial dystonic seizures and subsequently developed encephalopathy. Brain magnetic resonance imaging revealed atypical unilateral hyperintense signals in the cerebral cortex and white matter. Intravenous corticosteroid pulse therapy effectively improved faciobrachial dystonic seizures and brain lesions.

LGI1 encephalitis–Behaviors predate movements: A case series

Abstract Anti-leucine-rich, glioma-inactivated (LGI1) autoimmune encephalitis is one of the autoimmune encephalitides with a distinct movement abnormality – faciobrachial dystonic seizures (FBDS). FBDS, being the clinching sign towards a clinical diagnosis, is known to occur at disease onset, and if left untreated, can lead to disabling cognitive impairment. In this case series, we describe three cases of LGI1 encephalitis presenting with behavioral abnormalities at onset for a significant period, compelling an alternative diagnosis preceding the onset of FBDS. In addition, it highlights that imaging could be normal in the initial stages of the disease, further making the diagnosis a challenge at an initial stage.

Basal ganglia hemorrhage associated with anti-LGI1 encephalitis with faciobrachial dystonic seizures (FBDS) a case report

Basal ganglia hemorrhage associated with anti-LGI1 encephalitis with faciobrachial dystonic seizures (FBDS) a case report

Paraneoplastic Neurologic Syndromes.

Progress is ongoing in understanding paraneoplastic neurologic disorders, with new syndromes and antibodies being described and more detailed evidence available to guide workup for diagnosis and treatment to improve outcomes. Many excellent reviews have summarized the molecular features of different antibodies, but this article emphasizes the clinical features of each syndrome that may help guide initial diagnosis and treatment, which often should occur before an antibody or cancer is found to confirm the diagnosis. Recent findings include updated diagnostic criteria with validated sensitivity and specificity, discovery of novel antibodies, and clinical findings that increase the likelihood of an underlying paraneoplastic disorder. Suggestive syndromes that have been recently identified include faciobrachial dystonic seizures and pilomotor auras in anti-leucine-rich glioma inactivated protein 1 encephalitis, extreme delta brush on EEG in N-methyl-d-aspartate (NMDA)-receptor encephalitis, déjà vu aura in anti-glutamic acid decarboxylase 65 (GAD65) encephalitis, and sleep disturbances in several disorders. In addition, there is confirmed utility of brain positron emission tomography (PET) and CSF markers, including carcinoembryonic antigen and oligoclonal bands, as well as improved tests for the presence of leptomeningeal cancer cells in CSF. Associations of cancer immunotherapies with paraneoplastic syndromes and herpes simplex virus encephalitis (and COVID-19) with NMDA-receptor encephalitis have been described. All neurologists should be aware of advances regarding paraneoplastic neurologic syndromes, as patients can present with a wide variety of neurologic symptoms and earlier diagnosis and treatment can improve outcomes.

Diagnostic Superiority of 18 F-FDG PET Over MRI in Detecting Anti-LGI1 Autoimmune Encephalitis : A Comparative Study With Insights Into Faciobrachial Dystonic Seizures Mechanisms and Recurrence Identification.

Our study aimed to investigate the utility of 18 F-FDG PET imaging in diagnosing and monitoring patients with anti-leucine-rich glioma-inactivated 1 antibody autoimmune encephalitis (anti-LGI1 AE). We also sought to understand the mechanisms of faciobrachial dystonic seizures (FBDSs). We analyzed 18 F-FDG PET scans from 50 patients with anti-LGI1 AE, using visual and semiquantitative methods, and compared these with 24 healthy controls. All patients tested positive for anti-LGI1 antibodies in serum or cerebrospinal fluid before PET imaging. The patients were divided into FBDS and non-FBDS groups to compare metabolic differences using voxel-based semiquantitative analysis. Finally, we separately analyzed PET images of patients with symptom recurrence. The sensitivity of 18 F-FDG PET was superior to MRI (97.9% vs 63.8%, respectively; P < 0.001). Semiquantitative analysis revealed hypermetabolism in the basal ganglia, medial temporal lobe, and brainstem, and hypometabolism in most neocortical regions compared with healthy controls. The FBDS group exhibited hypometabolism in the frontal and temporal lobes compared with the non-FBDS group. Among 7 recurrent patients, 3 were confirmed as recurrence and 3 as sequelae by PET. One patient relapsed shortly after discontinuing corticosteroids when PET indicated active lesions. 18 F-FDG PET scans were more sensitive than MRI in detecting anti-LGI1 AE, which displayed a pattern of hypermetabolism in the basal ganglia and medial temporal lobe, as well as neocortex hypometabolism. Hypometabolism in the frontal and temporal lobes was associated with FBDS. Furthermore, 18 F-FDG PET scans can differentiate recurrence from sequelae and guide the timing of immunotherapy cessation.

A Prospective Observational Study of Autoimmune Encephalitis in Northwestern India.

Autoimmune encephalitis (AIE) is a group of rare, increasingly recognized, potentially reversible, noninfectious causes of unexplained encephalitis. It affects any age-group and has a plethora of clinical presentations, the most common being the neuropsychiatric manifestation. The diagnosis of this entity at the right time and proper treatment with immunotherapy can save many lives. In this study, we describe the demographic profile, clinical spectrum, diagnosis, and treatment of 42 patients with features of AIE. This is a prospective study where 42 cases were selected from a tertiary care center in Northwestern India. Patients with suspected AIE underwent detailed clinical assessment, routine blood tests, magnetic resonance imaging (MRI) brain, electroencephalography (EEG), cerebrospinal fluid (CSF) study, and autoimmune profile in blood and CSF. Screening for malignancy was done in all patients with computer tomography (CT) thorax and abdomen and tumor markers. Among 42 patients, males, and females were almost equally affected. The mean age of onset was 31 years. Anti-N-methyl-D-aspartate receptor (anti-NMDAR) Encephalitis was the commonest of all AIE (57%) followed by anti-leucine-rich glioma inactivated-1 (anti-LGI-1) related AIE (11.9%), anti-contactin-associated protein 2 (anti-CASPR2) related AIE (4.7%), and steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) related to antithyroid peroxidase (anti-TPO) antibody (2.3%). Neuropsychiatric manifestation is the commonest. The seizure was noted in around 72% of patients, the commonest in the anti-NMDAR group. Faciobrachial dystonic seizure (FBDS) was noted in all five anti-LG1-1 encephalitis patients. CSF abnormalities were seen in 33.3% of patients in the form of pleocytosis or raised protein, or both. MRI abnormality was seen in 52% of patients. EEG was abnormal in 10% of patients, and delta brush was noted in three anti-NMDAR patients. All patients received immunotherapy in the form of intravenous immunoglobulin (IVIg) or pulse IV methylprednisolone (IVMPS), or both. Two patients nonresponsive to IVIg and IVMPS received rituximab. Almost all patients responded to immunotherapy. Autoimmune encephalitis (AIE), a potentially treatable immune-responsive entity, is a common neurological problem and may be an answer to a large number of cases having unexplained encephalitis. Good clinical acumen and knowledge are required for early diagnosis and treatment of this potentially reversible disorder. How to cite this article: Sharma B, Paul M, Bagaria AK. A Prospective Observational Study of Autoimmune Encephalitis in Northwestern India. J Assoc Physicians India 2023;71(9):39-44.

Heterogeneity of clinical features, EEG and brain imaging findings in anti-leucine-rich glioma-inactivated protein 1 autoimmune encephalitis: a retrospective case series study and review of the literature

BackgroundAnti-leucine-rich glioma-inactivated 1 (LGI-1) autoimmune encephalitis (AE), characterized by rapid decline of memory, seizures, and neuropsychiatric abnormalities, is a rare but devastating disorder. Early diagnosis and treatment are essential to prevent long-term sequelae. In this report, we provide a detailed description of clinical characteristics, laboratory test results, imaging, and electroencephalography (EEG) findings, as well as treatment responses of eight patients with anti-LGI-1 AE treated at our center.Case presentationAt the onset, all eight patients presented with confusion/memory deterioration, seizures (including faciobrachial dystonic seizures or other types of seizure), and behavioral changes such as hallucination, paranoia, and anxiety. Four patients were found with severe hyponatremia. Anti-LGI1 antibodies were detected in the cerebrospinal fluid and/or serum of all patients. For patients with faciobrachial dystonic seizures, no discernible scalp EEG change was detected, while EEG recording of patients experiencing other types of seizure showed focal slowing, focal epileptiform discharges, and focal onset seizures. All patients showed abnormal brain magnetic resonance imaging signals, mainly involving the mesial temporal lobe and the hippocampus. In addition, one patient also experienced fulminant cerebral edema during the acute phase of the illness. All patients received immunotherapy and anti-seizure medications and achieved good seizure control. Nevertheless, these patients continued to experience cognitive impairment during their long-term follow-ups.ConclusionsThe care of anti-LGI1 AE patients requires rapid evaluation, prompt initiation of immunotherapy, and long-term follow-up. The long-term presence of neurocognitive complications observed in these patients underline the importance of developing reliable biomarkers that can distinguish between different subtypes of this disease with heterogeneous clinico-electrographico-radiological features. Further research is needed to understand the molecular mechanisms underlying the heterogeneity, in order to facilitate development of more effective treatments for anti-LGI1 AE.

Efficacy of immunotherapy and prognosis in anti-LGI1 encephalitis patients: A meta-analysis.

To assess the efficacy and safety of immunotherapy for LGI1 antibody encephalitis, and consider the predictors of poor outcomes following immunotherapy. We searched PubMed and Embase for articles reporting the immunotherapy data of anti-LGI1 encephalitis patients. The proportions of patients with poor outcomes (modified Rankin Scale [mRS] score > 2) at 3 months, 12 months, and the last follow-up, as well as the odds ratio [OR] of predictors were pooled. The review included 162 articles with 1066 patients. The proportion of patients with poor functional outcomes was 21% at 3 months, 14% at 12 months, and 14% at the last follow-up after receiving immunotherapy. The proportion of patients with reported relapse was 16.6%. The mean duration from onset to the first relapse was 15.6 months. Predictors significantly associated with poor outcomes were age (increase of 1 year), the presence of cognitive impairment, and CSF LGI1 antibody positive. We did not find a statistically significant association between the worst mRS score in the acute phase, the presence of faciobrachial dystonic seizures (FBDS), days from symptom onset to immunotherapy, second-line treatment, maintenance immunotherapy, or follow-up time and outcomes. Although most patients respond to immunotherapy, a minority of patients still have poor outcomes. Advanced age, cognitive impairment, and CSF LGI1 antibody positive are associated with an increased risk of poor outcomes. However, due to the insufficiency of the data, these conclusions need to be interpreted with caution.

Clinical characteristics of Leucine-rich glioma-inactivated protein 1 antibody-mediated autoimmune encephalitis in a 6-year-old girl: case report and literature reviews

BackgroundAutoimmune encephalitis related to the leucine-rich glioma-inactivated protein 1(LGI1) antibody is the most prevalent in older adults, manifesting as seizures, faciobrachial dystonic seizures (FBDS), cognitive impairment, memory disturbance, hyponatremia and neuropsychiatric disorders. However the data pertaining to children affected by the disease is still limited.Case presentation and literature reviewsThis study presents a detailed report of a 6-year-old Chinese girl who experienced nose aches and faciobrachial dystonic seizures (FBDS). Electrolyte testing revealed that she had hyponatremia and brain MRI showed an abnormality in the left temporal pole. Additionally, anti-LGI1 antibodies were detected in both her serum (1:100) and CSF (1:30). The patient was treated with immunotherapy and symptom management, which proved effective. Furthermore, we provide a summary of 25 pediatric cases of anti-LGI1 encephalitis. Pediatric patients rarely exhibited FBDS and hyponatremia, and some cases presented with isolated syndromes. But the therapeutic outcomes of pediatric patients were generally good.ConclusionsIn this report, we describe a patient who developed a rare symptom of nose aches possibly as one of symptoms of anti-LGI1 encephalitis, which highlights the possibility of atypical symptoms in children that may be misdiagnosed. Reviewing the literature, the clinical features differed between pediatric and adult cases. Therefore, it is crucial to collect and analyze data from more cases to promote accurate diagnosis and timely treatment.

P.026 Frontal cognitive-behavioural deficits in patients with anti-leucine-rich glioma-inactivated protein 1 antibody encephalitis

Background: Cognitive impairment is a common manifestation of anti-LGI1 encephalitis and is typically defined as prominent memory deficits. We frequently encounter frontal cognitive-behavioural deficits when evaluating these patients, but this has yet to be well described in the literature. Methods: Patients with anti-LGI1 encephalitis were retrospectively identified from three tertiary centres in Toronto, Ontario between 2013 and 2022. Their medical records were evaluated and frontal features were categorized based on diagnostic criteria for behavioural variant frontotemporal dementia (bvFTD). Results: Nineteen patients were identified (median age 60 years [range 18–84]; 10 [52.6%] male). Eighteen (94.7%) had frontal cognitive-behavioural symptoms. Two developed these symptoms during treatment with steroids and were excluded from further analysis. The remaining 16 presented with behavioural disinhibition (n=13), apathy or inertia (n=6), perseverative, stereotyped or compulsive/ritualistic behaviours (n=6), hyperorality and dietary changes (n=4), a neuropsychological profile with predominant deficits in executive tasks (n=4), and loss of sympathy or empathy (n=4). Nine (47.3%) met diagnostic criteria for possible bvFTD. Anterograde memory impairment was common (n=14). Of the 16 patients with frontal features, 6 had faciobrachial dystonic seizures. Conclusions: Patients with anti-LGI1 encephalitis exhibit frontal cognitive-behavioural symptoms in addition to memory impairment. Clinicians should consider anti-LGI1 encephalitis in the differential diagnosis of bvFTD.

Voltage-Gated Potassium Channels (VGKC) Complex-Associated Disorders: Anti-LGI1 Encephalitis and Anti-Caspr2 Encephalitis

Autoantibodies against LGI1 and Caspr2 complexed with voltage-gated potassium channels (VGKC) cause limbic encephalitis. Anti-LGI1 encephalitis progresses in a subacute course with memory impairment, disorientation, and focal epileptic seizures. Anti-LGI1 encephalitis is preceded by faciobrachial dystonic seizures (FBDS), which are specific involuntary movements and frequently complicated by hyponatremia due to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Neutralization of LGI1 by anti-LGI1 antibodies reduces AMPA receptors and induces epileptic seizures and memory impairment. Anti-Caspr2 encephalitis (Morvan's syndrome) is associated with limbic symptoms, severe autonomic disorders, muscle cramps and burning extremity pain due to peripheral nerve hyperexcitability. Thymomas and other malignant tumors may be complicated, and search for them is necessary. Anti-Caspr2 antibodies bind to Caspr2 on the surface of afferent cells in the dorsal root ganglion, and internalization of VGKCs causes a decrease in the K+ current, resulting in neuronal hyperexcitation and severe pain. Early immunotherapeutic intervention may improve the prognosis of these diseases, and measuring these autoantibodies should be performed in the presence of specific clinical signs, even with normal cerebrospinal fluid findings.

Monitoring Faciobrachial Dystonic Seizures with Wearable Devices (P5-5.015)

<h3>Objective:</h3> This study sought to assess whether faciobrachial dystonic seizures (FBDS) can be reliably identified and differentiated from normal nocturnal arousals using a wrist-worn device. <h3>Background:</h3> Detection of FBDS in patients with Leucine-rich glioma inactivated-1 (LGI1-IgG) associated autoimmune encephalitis is challenging due to high event frequency and lack of a robust EEG correlate. Wearable devices may provide a convenient, noninvasive means to measure these events and provide an objective seizure diary. <h3>Design/Methods:</h3> Two LGI1-IgG seropositive patients (P1 and P2) and four control subjects, wearing Empatica E4 devices, were recruited for this study. Two eight-hour sleep periods of each patient: pre- and post-treatment, were analyzed. An algorithm was developed based on accelerometry (ACC) signals to detect events of interest. After event identification, we calculated the ACC magnitude, duration, and electrodermal activity (EDA) characteristics of detected events. Presently, we are actively expanding the patient cohort and are investigating machine learning methods to improve the accuracy of event detection. <h3>Results:</h3> Statistically significant differences were found in device signals pre- and post-treatment, and between FBDS events in LGI1-IgG and nocturnal arousals in control subjects. The frequency of actigraphy events was higher in both patients (P1: pre-treatment 13.93±3.82 ev/h, post-treatment 9.66±3.37 ev/h; P2: pre-treatment 26.21±13.16 ev/h, post-treatment 29.06±9.79 ev/h), than controls (3.47±2.77 ev/h). For ACC magnitude and event duration, the medians were lower post-treatment and significantly lower for ACC magnitude in P2. Post-treatment, significant differences were only observed between controls and P1. For EDA activity, tonic and phasic components for controls were significantly lower than for patients pre-treatment. Additionally, means and medians decreased post-treatment in both patients. <h3>Conclusions:</h3> Robust characteristics were identified in actigraphy and EDA signals from a wrist-worn device during FBDS events. This evidence suggests an accurate monitor can be developed to automatically detect FBDS, providing objective measurements for treatment guidance and clinical decisions. <b>Disclosure:</b> Dr. Cui has nothing to disclose. Dr. Faust has nothing to disclose. Boney Joseph has nothing to disclose. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Dubey has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AGRIMS. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Advances in Neurology . Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Moffit Cancer Center . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Brinkmann has received personal compensation in the range of $0-$499 for serving as a Consultant for Otsuka Pharmaceuticals. Dr. Brinkmann has stock in Cadence Neuroscience. The institution of Dr. Brinkmann has received research support from Epilepsy Foundation of America. The institution of Dr. Brinkmann has received research support from National Institutes of Health. The institution of Dr. Brinkmann has received research support from National Institutes of Health. The institution of Dr. Brinkmann has received research support from UNEEG A/S. The institution of Dr. Brinkmann has received research support from Seer Medical Pty. Dr. Brinkmann has received intellectual property interests from a discovery or technology relating to health care. Dr. Brinkmann has a non-compensated relationship as a Co-Investigator with Medtronic Inc. that is relevant to AAN interests or activities.

A Pediatric Case of LGI1 Autoimmune Encephalitis Presenting with Faciobrachial Dystonic Seizures (P5-5.014)

<h3>Objective:</h3> NA <h3>Background:</h3> 15-year-old male presented with acute behavioral changes (agitation, confusion, declining grades), frequent falls, and abnormal movements involving the right corner of the mouth, cheek, arm and hand. His lower face appeared to be pulling to the right with concomitant flexion of the ipsilateral elbow and wrist in a motion that brought his hand close to his face <h3>Design/Methods:</h3> NA <h3>Results:</h3> Continuous EEG demonstrated approximately 70 seizures with either right or left rhythmic delta activity and superimposed spikes with associated twitching or dystonia in the contralateral arm or hand. MRI imaging showed T2 hyperintensity of the left hippocampus and amygdala. His seizures were controlled after loading 3 ASM’s (lacosamide, levetiracetam, valproate) followed by IVIG and methyl prednisolone administration. The diagnosis was confirmed by Mayo autoimmune encephalitis panel that was positive in the CSF and serum for LGI1 (leucine-rich glioma-inactivated 1) antibody. <h3>Conclusions:</h3> LGI1 autoimmune encephalitis is the second most common autoimmune encephalitis after NMDA(N-Methyl-D-aspartate). It is most commonly seen in middle aged men and estimated to occur in 0.83 per million. LGI1 autoimmune encephalitis is associated with multiple seizure types including focal seizures and tonic clonic seizures. The most distinctive feature of LGI1 autoimmune encephalitis is faciobrachial dystonic seizures that have been reported extensively in adult patients. LGI1 autoimmune encephalitis with seizures is exceedingly rare in the pediatric population. We found only 6 reported cases. Our case is the first reported faciobrachial dystonic seizures at presentation in a pediatric patient. <b>Disclosure:</b> Dr. Fields has nothing to disclose. Dr. Dalvi has nothing to disclose. Dr. Duberstein Coad has nothing to disclose. Dr. Eizadkhah has nothing to disclose. Dr. Moshe has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier/Neurobiology Of Disease. Dr. Moshe has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for MedLink. Dr. Moshe has received publishing royalties from a publication relating to health care. Dr. Moshe has received personal compensation in the range of $500-$4,999 for serving as a Reviewer of study sections with NINDS.

Frontal cognitive-behavioural deficits in patients with anti-leucine-rich glioma-inactivated protein 1 antibody encephalitis (S22.004)

<h3>Objective:</h3> To determine the prevalence of a frontal cognitive-behavioural phenotype in patients with anti-leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis. <h3>Background:</h3> Cognitive impairment is a common manifestation of anti-LGI1 encephalitis and is typically defined as prominent memory deficits. We frequently encounter frontal cognitive-behavioural deficits when evaluating these patients, but this has yet to be well described in the literature. <h3>Design/Methods:</h3> We retrospectively identified patients from three tertiary centres in Toronto, Ontario who were diagnosed with anti-LGI1 encephalitis between October 2013 and September 2022. Patient electronic medical records were evaluated for cognitive features and frontal features were categorized based on the diagnostic criteria for behavioural variant frontotemporal dementia (bvFTD). <h3>Results:</h3> Fifteen patients were identified (median age 65 years [range 18–84]; 8 [53.3%] male). Fourteen (93.3%) patients had cognitive symptoms that localized to the frontal lobe. Two developed these symptoms during treatment with steroids and were therefore excluded from further analysis. The remaining 12 patients presented with behavioural disinhibition (n=11), apathy or inertia (n=5), perseverative, stereotyped or compulsive/ritualistic behaviours (n=4), hyperorality and dietary changes (n=4), a neuropsychological profile with predominant deficits in executive tasks (n=4), and loss of sympathy or empathy (n=1). Seven (46.7%) met diagnostic criteria for possible bvFTD. Of these, 3 had significant functional decline and none had neuroimaging findings consistent with bvFTD. Anterograde memory impairment was common (n=11), and patients also presented with language deficits (n=3) and difficulties with spatial navigation (n=3). Of the 12 patients with frontal symptoms, only 5 had faciobrachial dystonic seizures. <h3>Conclusions:</h3> Patients with anti-LGI1 encephalitis can exhibit frontal cognitive-behavioural symptoms in addition to memory impairment, and screening for these features on clinical assessment may help to identify the diagnosis. Clinicians should also consider anti-LGI1 encephalitis in the differential diagnosis of bvFTD. <b>Disclosure:</b> Dr. Lee has nothing to disclose. Dr. Climans has nothing to disclose. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Parabon Nanolabs. The institution of Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for DynaMed (EBSCO Health). Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Barrow Law. Dr. Day has stock in ANI Pharmaceuticals. The institution of Dr. Day has received research support from National Institutes of Health / NIA. The institution of Dr. Day has received research support from Chan Zuckerberg Initiative. The institution of Dr. Day has received research support from Alzheimer’s Association. The institution of Dr. Day has received research support from National Institutes of Health / NINDS. The institution of Dr. Day has received research support from Horizon Therapeutics. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Presenter at Annual Meeting (CME) with American Academy of Neurology. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Content Development (CME) with PeerView, Inc. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving as a Content Development (CME) with Continuing Education, Inc. Dr. Day has a non-compensated relationship as a Clinical Director with AntiNMDA Receptor Encephalitis Foundation that is relevant to AAN interests or activities. Dr. Hebert has nothing to disclose. Dr. Lapointe has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Ramos has nothing to disclose. The institution of Dr. Steriade has received research support from NIH. The institution of Dr. Steriade has received research support from Dorris Duke Fund to Retain Clinician Scientists. Dr. Wennberg has nothing to disclose. Dr. Muccilli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Muccilli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Muccilli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for EMD Serono. Dr. Tang-Wai has nothing to disclose.