[Clinical features of five Japanese cases with leucine-rich glioma inactivated-1 (LGI1) antibody-positive encephalitis].

We studied the clinical features of five Japanese cases with leucine-rich glioma inactivated-1 (LGI1) antibody-positive encephalitis. Their symptoms included seizures, hallucinations, memory impairment, apathy, anxiety, agitation, faciobrachial dystonic seizure (FBDS), and ictal piloerection. All five patients showed hippocampal fluid attenuated inversion recovery (FLAIR) hyperintensity on brain MRI even though their cell counts of cerebrospinal fluid (CSF) were normal range. Four patients had syndrome of inappropriate secretion of antidiuretic hormone. One patient with FBDS also showed basal ganglia lesion on her brain MRI. Sodium channel blockers apparently lowered the frequency of FBDS. One patient had a thyroid cancer and underwent thyroidectomy. Substantial response to immunotherapy was seen in four out of five cases. At follow-up ≥2 years, all five patients had never relapsed. In cases of limbic encephalitis with normal CSF cell counts and hyponatremia, we should consider LGI1 antibody-positive encephalitis and conduct immunotherapy immediately.

Stiff Person Syndrome and GAD Antibody-Spectrum Disorders.

OBJECTIVE: Antibodies against glutamic acid decarboxylase (GAD), originally associated with stiff person syndrome (SPS), define the GAD antibody-spectrum disorders that also include cerebellar ataxia, autoimmune epilepsy, limbic encephalitis, progressive encephalomyelitis with rigidity and myoclonus (PERM), and eye movement disorders, all of which are characterized by autoimmune neuronal excitability. This article elaborates on the diagnostic criteria for SPS and SPS spectrum disorders, highlights disease mimics and misdiagnoses, describes the electrophysiologic mechanisms and underlying autoimmunity of stiffness and spasms, and provides a step-by-step therapeutic scheme. LATEST DEVELOPMENTS: Very-high serum GAD antibody titers are diagnostic for GAD antibody-spectrum disorders and also predict the presence of GAD antibodies in the CSF, increased intrathecal synthesis, and reduced CSF γ-aminobutyric acid (GABA) levels. Low serum GAD antibody titers or the absence of antibodies generates diagnostic challenges that require careful distinction in patients with a variety of painful spasms and stiffness, including functional neurologic disorders. Antibodies against glycine receptors, first found in patients with PERM, are seen in 13% to 15% of patients with SPS, whereas amphiphysin and gephyrin antibodies, seen in 5% of patients with SPS spectrum disorders, predict a paraneoplastic association. GAD-IgG from different SPS spectrum disorders recognizes the same dominant GAD intracellular epitope and, although the pathogenicity is unclear, is an excellent diagnostic marker. The biological basis of muscle stiffness and spasms is related to autoimmune neuronal hyperexcitability caused by impaired reciprocal γ-aminobutyric acid-mediated (GABA-ergic) inhibition, which explains the therapeutic response to GABA-enhancing agents and immunotherapies. ESSENTIAL POINTS: It is essential to distinguish SPS spectrum disorders from disease mimics to avoid both overdiagnoses and misdiagnoses, considering that SPS is treatable if managed correctly from the outset to prevent disease progression. A step-by-step, combination therapy of GABA-enhancing medications along with immunotherapies ensures prolonged clinical benefits.

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

BACKGROUND: Leucine-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. METHODS: We 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. RESULTS: Both 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. CONCLUSIONS: This 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.

Study on clinical features and factors related to long-term outcomes of antibody-negative autoimmune encephalitis.

OBJECTIVE: To delineate the clinical characteristics of antibody-negative autoimmune encephalitis (AE) and to investigate factors associated with long-term outcomes among antibody-negative AE. METHODS: Patients diagnosed with antibody-negative AE were recruited from January 2016 to December 2022 at the Second Xiangya Hospital of Central South University. The study assessed the long-term outcomes of antibody-negative AE using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Predictors influencing long-term outcomes were subsequently analyzed. External validation of RAPID scores (refractory status epilepticus [RSE], age of onset ≥60 years, ANPRA [antibody-negative probable autoimmune encephalitis], infratentorial involvement, and delay of immunotherapy ≥1 month) was performed. RESULTS: In total, 100 (47 females and 53 males) antibody-negative AE patients were enrolled in this study, with approximately 49 (49%) experiencing unfavorable long-term outcomes (mRS scores ≥3). Antibody-negative AE was subcategorized into ANPRA, autoimmune limbic encephalitis (LE), and acute disseminated encephalomyelitis (ADEM). Psychiatric symptoms were prevalent in LE and ANPRA subtypes, while weakness and gait instability/dystonia were predominant in the ADEM subtype. Higher peak CASE scores (odds ratio [OR] 1.846, 95% confidence interval [CI]: 1.163-2.930, p = 0.009) and initiating immunotherapy within 30 days (OR 0.210, 95% CI: 0.046-0.948, p = 0.042) were correlated with long-term outcomes. Receiver operating characteristic (ROC) analysis returned that the RAPID scores cutoff of 1.5 best discriminated the group with poor long-term outcomes (sensitivity 85.7%, specificity 56.9%). INTERPRETATION: The ANPRA subtype exhibited poorer long-term outcomes compared to LE and ADEM subtypes, and early immunotherapy was crucial for improving long-term outcomes in antibody-negative AE. The use of RAPID scoring could aid in guiding clinical decision making.

Seizure characteristics and outcomes in patients with neurological conditions related to high-risk paraneoplastic antibodies.

OBJECTIVE: Seizures are a common manifestation of paraneoplastic neurologic syndromes. The objective of this study was to describe the seizure characteristics and outcomes in patients with high-risk paraneoplastic autoantibodies (>70% cancer association) and to determine factors associated with ongoing seizures. METHODS: Patients from 2000 to 2020 with seizures and high-risk paraneoplastic autoantibodies were retrospectively identified. Factors associated with ongoing seizures at last follow-up were evaluated. RESULTS: Sixty patients were identified (34 males, median age at presentation = 52 years). ANNA1-IgG (Hu; n = 24, 39%), Ma2-IgG (n = 14, 23%), and CRMP5-IgG (CV2; n = 11, 18%) were the most common underlying antibodies. Seizures were the initial presenting symptom in 26 (43%), and malignancy was present in 38 (63%). Seizures persisted for >1 month in 83%, and 60% had ongoing seizures, with almost all patients (55/60, 92%) still being on antiseizure medications at last follow-up a median of 25 months after seizure onset. Ongoing seizures at last follow-up were associated with Ma2-IgG or ANNA1-IgG compared to other antibodies (p = .04), highest seizure frequency being at least daily (p = .0002), seizures on electroencephalogram (EEG; p = .03), and imaging evidence of limbic encephalitis (LE; p = .03). Death occurred in 48% throughout the course of follow-up, with a higher mortality in patients with LE than in those without LE (p = .04). Of 31 surviving patients at last follow-up, 55% continued to have intermittent seizures. SIGNIFICANCE: Seizures in the setting of high-risk paraneoplastic antibodies are frequently resistant to treatment. Ongoing seizures are associated with ANNA1-IgG and Ma2-IgG, high seizure frequency, and EEG and imaging abnormalities. Although a subset of patients may respond to immunotherapy and achieve seizure freedom, poor outcomes are frequently encountered. Death was more common among patients with LE.

Rare Association of Autoimmune Limbic Encephalitis and Stiff Person Syndrome.

Antibodies to Glutamic Acid Decarboxylase (GAD) have been implicated in the pathogenesis of both autoimmune Limbic Encephalitis (LE) and Stiff Person Syndrome (SPS). However, their association is quite rare. We present a case of a 48-year-old Caucasian female who presented with symptoms of recurrent severe headaches, behavioral and cognitive dysfunction, and an episode of seizure. She was found to have high titers of anti-GAD65 antibodies in both cerebrospinal fluid and serum. She was diagnosed with LE and SPS, and was started on immunosuppressive therapy with steroids and intravenous immunoglobulins (IVIG). The patient responded well to treatment with improvement in her symptoms.

[Paraneoplastic Neurologic Syndromes].

Paraneoplastic neurologic syndromes (PNS) are a group of neurological disorders that are possibly caused by immunological mechanisms triggered by an underlying tumor that involves every part of the nervous system. Autoantibodies were categorized according to the risk of cancer association. Antibodies against intracellular proteins are excellent markers for tumor detection, however, without functional roles in neuronal loss, the direct effector of neuronal damage is thought to be cytotoxic T cells. The frequently associated symptoms include limbic encephalitis, cerebellar ataxia and sensory neuronopathy. The associated tumors are mainly small-cell lung cancer, breast/ovarian/uterine cancers, and thymoma. Timely diagnosis, prompt immunotherapy, and treatment of the underlying tumor are essential for managing PNS. However, we need to be cautious about the high frequency of false-positive/negative results of antibodies using commercial antibody tests. This highlight the importance of the careful evaluation of clinical features. Recently, PNS emerged after immune check point inhibitor administration, and this became a subject of attention exploring its pathogenesis. Other basic studies to understand the immunological background of PNS have been progressing.

Anti-amphiphysin encephalitis: Expanding the clinical spectrum.

Objective: An analysis of the clinical features of autoimmune encephalitis accompanied by anti-amphiphysin antibodies. Methods: The data of encephalitis patients with anti-amphiphysin antibodies were retrospectively evaluated, including demographics, neurological and laboratory findings, imaging, treatment, and prognostic predictions. Results: Ten patients aged between 29 and 78 years (median age 52 years) were included. The male: female ratio was 4:6. Limbic encephalitis was found in nine patients while epileptic seizures were present in seven patients. All patients showed anti-amphiphysin antibody positivity in sera while one ninth was positive for CSF antibody. The EEG findings were abnormal, including reductions in background activity, and the presence of diffuse slow waves, sharp waves, and spikes and waves. Five patients showed signs of increased T2 signals in the medial temporal lobe on MRI while PET showed either hyper- or hypo-metabolic changes in several brain regions, including the temporal lobe, hippocampus, basal ganglia, frontal and parietal cortices. Nine of ten patients were treated with immunotherapy, with improvements of varying degrees. There was a significant reduction in seizure frequency, and all patients were seizure-free at last follow-up. Conclusion: Autoimmune encephalitis with anti-amphiphysin antibodies has a variety of clinical manifestations. The most common symptom is limbic encephalitis. Although relief from seizures can be achieved relatively easily, many patients suffer psychiatric, cognitive, and sleep sequelae. The disease was found to be associated with a lower incidence of cancer than has been previously reported for paraneoplastic neurologic syndromes.

A feline model of spontaneously occurring autoimmune limbic encephalitis.

Autoimmune encephalitis (AE) is an important cause of encephalitis in humans and occurs at a similar rate to infectious encephalitis. It is frequently associated with antibodies against the extracellular domain of neuronal proteins. Among human AE, that with antibodies against leucine-rich glioma-inactivated 1 (LGI1) is one of the most prevalent forms, and was recently described in cats with limbic encephalitis (LE). In this study, we describe a large cohort (n = 32) of cats with AE, tested positive for voltage gated potassium channel (VGKC)-antibodies, of which 26 (81%) harboured LGI1-antibodies. We delineate their clinical and paraclinical features as well as long-term outcomes up to 5 years. Similar to human cases, most cats with LGI1-antibodies had a history of focal seizures (83%), clustering in the majority (88%), with interictal behavioural changes (73%). Among feline AE patients, there was no seizure type or other clinical characteristic that could distinguish LGI1-antibody positive from negative cats, unlike the pathognomic faciobrachial dystonic seizures seen in humans. Although six cats were euthanased in the first year for epilepsy-associated reasons, those attaining at least 1-year survival had good seizure control and quality of life with appropriate veterinary care and medication. Acute-phase immunotherapy (prednisolone) was given to the most severely unwell cases and its effect is retrospectively evaluated in 10 cats. Our data show LGI1-antibodies are an important cause of feline encephalitis, sharing many features with human AE. Further research should examine optimal therapeutic management strategies and the cause of LE in seronegative cats, building on paradigms established in the counterpart human disease.

Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response.

BACKGROUND: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis. METHODS: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays. RESULTS: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome. CONCLUSIONS: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.

Review and meta-analysis of neuropsychological findings in autoimmune limbic encephalitis with autoantibodies against LGI1, CASPR2, and GAD65 and their response to immunotherapy.

OBJECTIVES: It is assumed that autoimmune limbic encephalitis (ALE) demonstrates distinct neuropsychological manifestations with differential responses to immunotherapy according to which associated autoantibody (AAB), if any, is identified. Towards investigating whether this is the case, this study aims to summarize respective findings from the primary literature on ALE with AABs binding to cell surface neural antigens and ALE with AABs against intracellular neural antigens. METHODS: We chose ALE with AABs against leucine-rich, glioma inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) as the most frequent cell surface membrane antigens, and ALE with AABs to Embryonic Lethal, Abnormal Vision, Like 1 (ELAVL) proteins (anti-Hu) and glutamic acid decarboxylase 65 (GAD65) as the most frequent intracellular neural antigens. The PubMed and Scopus databases were searched on March 1st, 2021 for neuropsychological test and -screening data from patients with ALE of these AAB-types. Findings were reviewed according to AAB-type and immunotherapy status and are presented in a review section and are further statistically evaluated and presented in a meta-analysis section in this publication. RESULTS: Of the 1304 initial hits, 32 studies on ALE with AABs against LGI1, CASPR2, and GAD65 reporting cognitive screening data could be included in a review. In ALE with AABs against LGI1, CASPR2 and GAD65, memory deficits are the most frequently reported deficits. However, deficits in attention and executive functions including working memory, fluency, and psychological function have also been reported. This review shows that ALE patients with AABs against both LGI1 and CASPR2 show higher percentages of neuropsychological deficits compared to ALE patients with AABs against GAD65 before and after initiation of immunotherapy. However, the methodologies used in these studies were heterogenous, and longitudinal studies were not comparable. Moreover, 21 studies including ALE patients with AABs against LGI1 and GAD65 were also suitable for meta-analysis. No suitable study on ALE with AABs against ELAVL proteins could be identified. Meta-Analyses could be executed for cognitive screening data and only partially, due to the small number of studies. However, in statistical analysis no consistent effect of AAB or immunotherapy on performance in cognitive screening tests could be found. CONCLUSION: Currently, there is no definite evidence supporting the notion that different AAB-types of ALE exhibit distinct neuropsychological manifestations and respond differently to immunotherapy. Overall, we could not identify evidence for any effect of immunotherapy on cognition in ALE. More systematic, in-depth and longitudinal neuropsychological assessments of patients with different AAB-types of ALE are required in the future to investigate these aspects.

Encefalitis límbica asociada a secreción inadecuada de hormona antidiurética. Reporte de un caso y revisión de la literatura / Limbic encephalitis associated with inappropriate secretion of antidiuretic hormone. A case report and literature review / Encefalite límbica associada à secreção inapropriada de hormônio antidiurético. Relato de caso e revisão da literatura

La encefalitis límbica (EL) autoinmune es una afección neurológica infrecuente de curso subagudo con manifestaciones neuropsicológicas. Actualmente el tratamiento inmunoterápico agudo o de mantenimiento es dirigido según el anticuerpo neural acompañante y la presencia o ausencia de cáncer. Presentamos el caso de una mujer de 52 años con hipotiroidismo autoinmune, síndrome de secreción inadecuada de hormona antidiurética (SIADH) e hiponatremia (hipoNa) persistente, con evolución progresiva de perdida de la memoria y crisis distónicas faciobraquiales (DFBC) a quien se le realiza un diagnóstico oportuno de encefalitis límbica. Recibió tratamiento intravenoso combinado en base a corticoides e inmunoglobulina con buena respuesta y morbilidad mínima neuropsicológica. El reconocimiento de esta patología permite un diagnóstico y tratamiento temprano, imprescindible para mejorar el pronóstico de estos pacientes.

Autoimmune limbic encephalitis is a rather unusual neurological condition with subacute progression and neuropsychological symptoms. Currently, acute or maintenance treatment with immunotherapy is targeted depending on the accompanying neural specific antibody and the presence or absence of cancer. The study presents the case of a 52-year-old woman suffering from autoimmune hypothyroidism, syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) and persistent hyponatremia, with progressive evolution which involved memory loss and faciobrachial dystonic seizures (FBDS). She was timely diagnosed with limbic encephalitis and was treated with intravenous combined corticosteroids and immunoglobulin therapy. Response was good, with minimum neuropsychological. Recognizing this condition allows for early diagnosis and treatment, what is key to improve the prognosis of these patients.

A encefalite límbica (LE) autoimune é uma condição neurológica rara de curso subagudo com manifestações neuropsiquiátrica. Atualmente, o tratamento com imunoterapia aguda ou de manutenção é orientado de acordo com o anticorpo neural e a presença ou ausência de câncer. Apresentamos o caso de uma mulher de 52 anos com hipotireoidismo autoimune, síndrome de secreção inapropriada de hormônio antidiurético e hiponatremia persistente, com evolução progressiva da perda de memória e crises distônicas faciobraquiais que foi diagnosticada oportunamente como encefalite límbica. Recebeu tratamento endovenoso combinado à base de corticoide e imunoglobulina com boa resposta e morbidade neuropsiquiátrica mínima. O reconhecimento desta patologia permite um diagnóstico e tratamento precoces, essenciais para melhorar o prognóstico desses pacientes.

Panhypopituitarism as the first sign of paraneoplastic limbic encephalitis in a patient with cured testicular cancer: a case report.

BACKGROUND: Paraneoplastic limbic encephalitis is a rare neurologic syndrome that affects patients with cancer and commonly presents with symptoms of personality changes, visual disturbances, seizures, vertigo, and memory loss. It has an immune-mediated pathophysiology and is associated with antibodies directed against both the tumor and limbic structures in the nervous system. Here, we report a case of paraneoplastic limbic encephalitis with an unusual presentation with initial symptoms of panhypopituitarism. CASE PRESENTATION: A 28-year-old Caucasian man with history of testicular cancer in remission for almost 2 years was admitted to our hospital for altered mental status, syncope, vertical gaze palsy, ataxia, and tremor. Three months prior to admission, he began to have initial symptoms of fatigue, weight gain, and hypogonadism. A few weeks before admission, he also developed worsening neurological symptoms that led him to present to the hospital. While hospitalized, he had an episode of syncope. Evaluation of his syncope revealed that he was hypovolemic due to polyuria, concerning for diabetes insipidus. While the patient did not meet criteria for diabetes insipidus, further endocrine laboratory testing to evaluate his central hormonal axes revealed panhypopituitarism. He also underwent a neurologic work-up with brain magnetic resonance imaging and lumbar puncture, with results consistent with encephalitis. He received high-dose steroids, plasmapheresis, and intravenous immunoglobulin, which did not significantly improve his physical examination or mental status. Extensive testing did not show any recurrence of his testicular cancer. Paraneoplastic antibodies were also ordered, with anti-Ma2 antibodies eventually returning positive, consistent with anti-Ma2 paraneoplastic limbic encephalitis. CONCLUSION: Paraneoplastic limbic encephalitis is often a difficult diagnosis due to its variable presentation and timeline of presentation, leading to delays in both diagnosis and treatment. While paraneoplastic limbic encephalitis usually presents with neurological symptoms, it may also present with panhypopituitarism. A high index of suspicion is warranted for paraneoplastic syndromes in patients with history of malignancy, even if the malignancy is in remission.

Limbic encephalitis.

Limbic encephalitis (LE) is a clinical syndrome defined by subacutely evolving limbic signs and symptoms with structural and functional evidence of mediotemporal damage in the absence of a better explanation than an autoimmune (or paraneoplastic) cause. There are features common to all forms of LE. In recent years, antibody(ab)-defined subtypes have been established. They are distinct regarding underlying pathophysiologic processes, clinical and magnetic resonance imaging courses, cerebrospinal fluid signatures, treatment responsivity, and likelihood of a chronic course. With immunotherapy, LE with abs against surface antigens has a better outcome than LE with abs to intracellular antigens. Diagnostic and treatment challenges are, on the one hand, to avoid overlooking and undertreatment and, on the other hand, to avoid overdiagnoses and overtreatment. LE can be conceptualized as a model disease for the consequences of new onset mediotemporal damage by different mechanisms in adult life. It may be studied as an example of mediotemporal epileptogenesis.

Nonparaneoplastic Anti-GAD Limbic Encephalitis: Seizure Outcome and Long-term Neuropsychological Follow-up After Immunotherapy.

Antibodies against glutamate decarboxylase (GAD-Abs), especially GAD65 antibodies, are associated with limbic encephalitis (LE) manifested by temporal lobe epilepsy and neuropsychological deficits. We present the case of a 42-year-old Greek woman with nonparaneoplastic anti-GAD LE, discussing the therapeutic management and highlighting the role of neuropsychological assessment. The patient underwent functional and structural brain studies and was investigated longitudinally over a 6-year period with a battery of neuropsychological tests that were designed to document her intellectual function and verbal and visual memory. The patient suffered from refractory temporal-impaired awareness seizures and memory impairment that was mediated by autoimmune nonparaneoplastic LE and comorbid autoimmune disorders (ie, Hashimoto thyroiditis and vitiligo). Neuroimaging studies demonstrated hyperintensities in the medial temporal lobes bilaterally on T2WI MRI sequences. Serial EEGs showed bitemporal intermittent delta activity as well as epileptiform discharges. Tumor blood markers and onconeural antibodies were negative. Immunological screening revealed extremely high GAD-Abs titers in both serum and CSF, as well as the presence of CSF oligoclonal bands. Neuropsychological testing revealed anterograde amnesia with relative preservation of more remote, premorbid memories. The patient underwent first-line immunotherapy followed by immunosuppressive maintenance treatment that led to a reduction of seizures, EEG improvement, and a significant decline in GAD-Abs titers. Neuropsychological evaluations at 5 months, 1 year, and 6 years posttreatment demonstrated improvement, particularly in recent memory and everyday functionality. In this case of anti-GAD LE, the long-term seizure reduction and the improvement of neuropsychological deficits were most likely related to the immunotherapy.

Great balls of fire! The basal ganglia on fire.

A 76-year-old man presented to the hospital with intermittent dizziness, memory impairment and jerky movements. Evaluation revealed them to be faciobrachial dystonic seizures and antibodies to voltage-gated potassium channel complexes were found. He was treated with intravenous methylprednisolone and rituximab, and made a remarkable recovery. Magnetic resonance imaging of the brain was normal, although positron emission tomography - computed tomography showed striking basal ganglia changes.

Clinical features, investigations, and outcomes of pediatric limbic encephalitis: A multicenter study.

OBJECTIVES: To describe the clinical presentation, investigations, management, and disease course in pediatric autoimmune limbic encephalitis (LE). METHODS: In this retrospective observational study, from the UK Childhood Neuroinflammatory Disease network, we identified children from six tertiary centers with LE <18 years old between 2008 and 2021. Clinical and paraclinical data were retrieved from medical records. RESULTS: Twenty-five children fulfilling LE criteria were identified, with median age of 11 years (IQR 8, 14) and median follow-up of 24 months (IQR 18, 48). All children presented with seizures; 15/25 (60%) were admitted to intensive care. Neuroimaging demonstrated asymmetric mesial temporal changes in 8/25 (32%), and extra-limbic changes with claustrum involvement in 9/25 (38%). None were positive for LGI1/CASPR2 antibodies (Abs), 2/25 were positive for serum anti-NMDAR Abs, and 2/15 positive for anti-Hu Abs; one died from relapsing neuroblastoma. Two children had serum and CSF anti-GAD antibodies. Initial immune therapy included steroids in 23/25 (92%), intravenous immunoglobulin (IVIg) in 14/25 (56%), and plasma exchange in 7/25 (28%). The commonest second-line treatment was rituximab in 15/25 (60%). Median duration of hospital admission was 21 days (IQR 11, 30). At last follow-up, 13/25 (52%) had refractory seizures and 16/25 (64%) had memory impairment. Six children (24%) had modified Rankin Scale (mRS) scores ≥3. There was no significant difference in mRS, or long-term cognitive and epilepsy outcomes in those who received rituximab versus those who did not. INTERPRETATION: A diagnosis of autoimmune LE was associated with significant morbidity and adverse outcomes in this pediatric cohort.

Immunotherapy-responsive Non-paraneoplastic Encephalitis with Antibodies against GAD, LGI1, and GABAA Receptor.

A 62-year-old man showed abnormal behavior. Brain magnetic resonance imaging revealed multifocal lesions on T2-weighted images. Initial screening revealed that he was seropositive for antibodies against glutamate decarboxylase, which usually indicates treatment resistance to autoimmune encephalitis (AE). Intensive immunosuppressive therapies, however, improved the neurological symptoms. In line with this, we also detected seropositivity for antibodies against leucine-rich glioma-inactivated 1 and gamma-aminobutyric acid A receptor (GABAAR). Brain imaging and treatment responsiveness suggested that antibodies against GABAAR were the main cause of symptoms. Furthermore, the patient showed the presence of triple anti-neural antibodies in the absence of malignancy and had a favorable clinical course.