anti-CASPR2 Encephalitis Research Articles

Clinical characteristics and outcomes of patients with antibody-related autoimmune encephalitis presenting with disorders of consciousness: A prospective cohort study.

To explore the clinical characteristics, short- and long-term functional outcomes, and risk factors for antibody-related autoimmune encephalitis (AE) in patients with disorders of consciousness (DoC). Clinical data were collected from AE patients admitted to Xuanwu Hospital of Capital Medical University from January 2012 to December 2021, and patients were followed up for up to 24 months after immunotherapy. A total of 312 patients with AE were included: 197 (63.1%) with anti-NMDAR encephalitis, 71 (22.8%) with anti-LGI1 encephalitis, 20 (6.4%) with anti-GABAbR encephalitis, 10 (3.2%) with anti-CASPR2 encephalitis, 10 (3.2%) with anti-GAD65 encephalitis, and 4 (1.3%) with anti-AMPAR2 encephalitis. Among these patients, 32.4% (101/312) presented with DoC, and the median (interquartile range, IQR) time to DoC was 16 (7.5, 32) days. DoC patients had higher rates of various clinical features of AE (p < .05). DoC was associated with elevated lumbar puncture cerebrospinal fluid (CSF) pressure, CSF leukocyte count, and specific antibody titer (p < .05). A high percentage of patients in the DoC group had a poor prognosis at discharge and at 6 months after immunotherapy (p < .001), but no significant difference in prognosis was noted between the DoC group and the non-DoC group at 12 and 24 months after immunotherapy. Dyskinesia (OR = 3.266, 95% CI: 1.550-6.925, p = .002), autonomic dysfunction (OR = 5.871, 95% CI: 2.574-14.096, and p < .001), increased CSF pressure (OR = 1.007, 95% CI: 1.001-1.014, p = .046), and modified Rankin scale (mRS) score ≥3 at the initiation of immunotherapy (OR = 7.457, 95% CI: 3.225-18.839, p < .001) were independent risk factors for DoC in AE patients. DoC is a relatively common clinical symptom in patients with AE, especially critically ill patients. Despite requiring longer hospitalization, DoC mostly improves with treatment of the primary disease and has a good long-term prognosis after aggressive life support and combination immunotherapy.

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.

Clinical features of 28 cases of anti-leucine-rich glioma-inactivated protein 1 encephalitis and anti-contactin-associated protein-like 2 encephalitis.

Autoimmune encephalitis arising from autoantibodies against leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) are rare and with high clinical heterogeneity. They are easily misdiagnosed and missing diagnosed. This study aims to explore the clinical characteristics, auxiliary examinations, therapies and prognosis of anti-LGI1 and anti-CASPR2 encephalitis. Seventeen anti-LGI1 and 11 anti-CASPR2 encephalitis patients who were admitted to the Department of Neurology, Xiangya Hospital, Central South University between January 2018 and January 2021 were collected and retrospectively analyzed. Autoimmune encephalitis related antibodies and paraneoplastic antibodies were screened in all patients. The clinical manifestations, results of laboratory tests, imaging features, treatments and outcomes of 2 encephalitis groups were analyzed and compared. In the anti-LGI1 encephalitis group, the age of 17 patients was 28-83 (53.18±19.08) years old, and the ratio of male to female was 9꞉8. There were 10 patients with cognitive impairment, 7 seizures, 4 faciobrachial dystonic seizures, and 1 psychiatric disturbance. Hyponatremia was observed in 7 patients. Eight patients had increased slow waves and 5 had epileptic discharge in electroencephalogram (EEG). Brain magnetic resonance (MRI) showed T2-weighted imaging (T2WI) and fluid attenuated inversion recovery (FLAIR) hyperintense signal in the temporal lobe, hippocampus and basal ganglia in 13 patients. In the anti-CASPR2 group, the age of 11 patients was 17-68 (47.18±16.20) years old, and the ratio of male to female was 5꞉6, with 7 limbic encephalitis, 1 Morvan syndrome, and 3 acquired neuromyotonia (NMT). Three patients had increased slow waves and 2 had epileptic discharge in EEG. Brain MRI showed T2WI and FLAIR hyperintense signal in the temporal lobe, hippocampus in 2 patients. Steroids, intravenous immunoglobin, and plasma exchange were administrated in 16 anti-LGI1 encephalitis and 8 anti-CASPR2 encephalitis patients with good therapeutic responses. Among them, 1 patient with anti-LGI1 encephalitis and 3 with anti-CASPR2 encephalitis were administrated with mycophenolate mofetil for immune maintenance therapy. No recurrences were observed in all patients with immunotherapy except for 2 patients who lost of follow-up. There were significant differences in cognitive impairment, hyponatremia, and brain MRI abnormalities between anti-LGI1 and anti-CASPR2 encephalitis patients (all P<0.05). Limbic encephalitis is a common syndrome in both anti-LGI1 and anti-CASPR2 encephalitis patients. Anti-CASPR2 encephalitis has a wider clinical spectrum than anti-LGI1 encephalitis, presenting as NMT and Morvan syndrome, which has a closer relationship with tumors. Both of these 2 antibodies associated disorders are sensitive to immunotherapy and have a good prognosis.

Clinical Characteristics and Short-Term Prognosis of Children With Antibody-Mediated Autoimmune Encephalitis: A Single-Center Cohort Study.

BackgroundThe incidence and prevalence of autoimmune encephalitis (AE) is gradually increasing in pediatric patients (between the ages of 3 months and 16 years). The aim of this retrospective observational study was to investigate the clinical characteristics and short-term prognosis of children with antibody-mediated AE at Hunan Children's Hospital.MethodsAntibody analysis of blood and/or cerebrospinal fluid was performed in suspected AE patients admitted to the Department of Neurology, Hunan Children's Hospital from June 2014 to June 2021. Ultimately, 103 patients were diagnosed with antibody-mediated AE and were enrolled in this study. Clinical data and corresponding demographic, clinical characteristics, laboratory and imaging data, treatment, and prognosis data were collected and analyzed.ResultsIn our study, 103 AE patients with antibody-positive were identified. The main subtype of AE in our cohort was anti-NMDAR encephalitis. Few patients have anti-CASPR2 encephalitis, anti-GABABR encephalitis, or anti-LGI1 encephalitis. In our AE patients, the most common clinical manifestations were behavioral symptoms, seizures, and involuntary movements, with seizures being the most common initial symptom. All patients underwent brain magnetic resonance imaging (MRI) and electroencephalography (EEG). Forty-five (43.7%) patients had abnormal MRI findings. And 96 (93.2%) patients had abnormal EEG results. All 103 patients were given first-line immunotherapy, 21 of which were also treated with the combination of the second-line immunotherapy. All surviving patients were followed up for at least 6 months. Seventy-seven patients recovered completely, 23 had sequelae of different degrees, and 3 died. Eight patients had one or more relapses during the follow-up period.ConclusionsAE is a treatable disease that can occur in children of all ages. The mortality rate is low, as most patients have a good response to immune therapy. Compared with the older children, infants and young children (≤ 3 years old) with anti-NMDAR encephalitis have a higher incidence of fever and status epilepticus, more severe condition, higher PICU admission rate and worse prognosis. AE patients with high maximum mRS scores and PICU admissions may require second-line immunotherapy.

Clinical features and outcomes of leucine-rich glioma-inactivated protein 1 and contactin protein-like 2 antibody-associated autoimmune encephalitis in a Chinese cohort

The present study aimed to investigate the clinical manifestations, epidemiological characteristics, and outcomes of Chinese patients with voltage-gated potassium channel complex (VGKC) antibody–associated encephalitis. Patients diagnosed with VGKC antibody-associated encephalitis at our institution between January 2016 and December 2020 were included in this study. We retrospectively evaluated their clinical features, auxiliary examination results, treatments details, long-term outcomes, and risk factors for poor outcome. Of the 91 included patients, 61 (67.78%) were men and 30 (32.97%) were women. The most common clinical symptoms were seizures (n = 63, 69.23%), memory deficits (n = 62, 68.13%), mental behavioral disorders (n = 29, 31.87%), and hyponatremia (n = 57, 62.64%). Although patients with anti- leucine-rich glioma-inactivated 1 (LGI1) (n = 76) and anti- contactin-associated protein-like 2 (CASPR2) encephalitis (n = 15) had similar clinical manifestations, the former were more diverse. In total, 86 (94.51%) patients were treated with immunotherapy. Over a median follow-up period of 25 months, there were no mortalities and 14 (15.38%) patients experienced a relapse. Univariate analysis indicated differences in sex, modified Rankin Scale scores at onset, movement disorders, central hypoventilation, and intensive care unit occupancy between the good- and poor- outcome groups. Patients with anti-LGI1 and anti-CASPR2 encephalitis showed similar clinical manifestations while presenting delineating characteristics. Those with VGKC antibody-associated diseases generally responded well to immunotherapy and demonstrated favorable clinical outcomes. Several factors affected the prognosis, and a long-term follow-up examination is necessary.

Human CASPR2 Antibodies Reversibly Alter Memory and the CASPR2 Protein Complex.

The encephalitis associated with antibodies against contactin-associated proteinlike 2 (CASPR2) is presumably antibody-mediated, but the antibody effects and whether they cause behavioral alterations are not well known. Here, we used a mouse model of patients' immunoglobulin G (IgG) transfer and super-resolution microscopy to demonstrate the antibody pathogenicity. IgG from patients with anti-CASPR2 encephalitis or healthy controls was infused into the cerebroventricular system of mice. The levels and colocalization of CASPR2 with transient axonal glycoprotein 1 (TAG1) were determined with stimulated emission depletion microscopy (40-70μm lateral resolution). Hippocampal clusters of Kv1.1 voltage-gated potassium channels (VGKCs) and GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) were quantified with confocal microscopy. Behavioral alterations were assessed with standard behavioral paradigms. Cultured neurons were used to determine the levels of intracellular CASPR2 and TAG1 after exposure to patients' IgG. Infusion of patients' IgG, but not controls' IgG, caused memory impairment along with hippocampal reduction of surface CASPR2 clusters and decreased CASPR2/TAG1 colocalization. In cultured neurons, patients' IgG led to an increase of intracellular CASPR2 without affecting TAG1, suggesting selective CASPR2 internalization. Additionally, mice infused with patients' IgG showed decreased levels of Kv1.1 and GluA1 (two CASPR2-regulated proteins). All these alterations and the memory deficit reverted to normal after removing patients' IgG. IgG from patients with anti-CASPR2 encephalitis causes reversible memory impairment, inhibits the interaction of CASPR2/TAG1, and decreases the levels of CASPR2 and related proteins (VGKC, AMPAR). These findings fulfill the postulates of antibody-mediated disease and provide a biological basis for antibody-removing treatment approaches. ANN NEUROL 2022;91:801-813.

Clinical characteristics, long-term functional outcomes and relapse of anti-LGI1/Caspr2 encephalitis: a prospective cohort study in Western China.

Objective:To study the clinical characteristics of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis and anti-contactin-associated protein-like 2 (Caspr2) encephalitis and to investigate factors associated with poor long-term neurological functional outcomes and relapse among patients in western China.Methods:In this single-center prospective cohort study, we consecutively enrolled patients with anti-LGI1 encephalitis and anti-Caspr2 encephalitis from April 2014 to February 2021. Patient outcomes were assessed using the modified Rankin scale. Predictors of long-term functional outcomes and relapse were analyzed.Results:Forty-four anti-LGI1 encephalitis patients [median age: 44 years, range: 18–82 years; females: 25 (56.8%)], 35 anti-Caspr2 encephalitis patients [median age: 43 years, range: 14–80 years; females: 19 (54.3%)], and 5 dual-positive patients [median age: 44 years, range: 36–58 years; females: 5 (100%)] were enrolled. Overall, 86.4% anti-LGI1 encephalitis patients and 80% anti-Caspr2 encephalitis had a favorable neurological functional outcome (mRS 0-2). Tumor occurrence and weight loss were associated with poor long-term functional outcomes in anti-LGI1 encephalitis, whereas in anti-Caspr2 encephalitis, predictors included behavioral disorder at acute phase, abnormalities in brain magnetic resonance imaging, higher modified Rankin scale scores at onset, poor response to the initial immunotherapy at 4 weeks, age at onset<30 years, and relapse (p<0.05). Overall, 13.6% of anti-LGI1 encephalitis patients and 20% of anti-Caspr2 encephalitis patients had at least one relapse. Sleep disorder at the acute phase was the risk factor of relapse in anti-LGI1 encephalitis, while female, age at onset <30 years, and behavioral disorder at acute phase were the risk factors of relapse in anti-Caspr2 encephalitis (log rank p<0.05).Conclusion:The clinical characteristics such as age, gender, and tumor occurrence rates of anti-LGI1 encephalitis and anti-Caspr2 encephalitis in western China are different from those in the Western countries. Most patients in our study had favorable long-term functional outcomes. The relapse rates are still high in both types of encephalitis, which warrants caution.

"Antibody of Unknown Significance" (AUS): The Issue of Interpreting Antibody Test Results.

"Antibody of Unknown Significance" (AUS): The Issue of Interpreting Antibody Test Results.

Cytokine changes during treatment of anti-Caspr2 encephalitis: a case report

BackgroundCytokines are effective molecules of immune reactions. They work in inflammatory sites as well as circulate in the blood. Cytokines in the cerebrospinal fluid have been suggested to be markers of autoimmune encephalitis and reflect disease progression. However, studies on blood cytokines in autoimmune encephalitis are scarce. We report a case presenting with serial changes in blood cytokine levels in a male patient with anti-contactin-associated protein 2 (Caspr2) encephalitis.Case presentationA 61-year-old man without systemic disease presented with ataxia and speech disturbance 1 week. After admission, he further developed visual hallucinations, psychosis, and consciousness deterioration. Brain magnetic resonance imaging and infection and tumor surveillances were negative. 18F-fluorodeoxyglucose positron emission tomography of brain revealed frontal and occipital hypometabolism and anterior cingulate gyrus and mesial temporal hypermetabolism. Autoimmune studies confirmed Caspr2 antibodies in his blood. After receiving a diagnosis of anti-Caspr2 encephalitis, the patient received steroids, plasmapheresis, and zonisamide. He recovered well and was totally independent 6 months after disease onset.A cytokine profiler array kit was used to investigate neuroimmune mechanisms during the disease course. Several cytokines showed significant changes in plasma levels, such as B cell activating factor for B cell proliferation; thymus and activation-regulated chemokine for T cell chemoattraction; soluble CD40 ligand for Th2 cell mediation; C5/C5a for complement activation; brain-derived neurotrophic factor for neuronal survival response; and dipeptidyl peptidase 4, retinol binding protein, dickkopf-related protein, and epidermal growth factor for response to environmental provocation. The concentration of cytokines was verified using Luminex multiplexing assay.ConclusionsDue to their easy accessibility, blood cytokines are potential biomarkers of autoimmune encephalitis. Based on the investigating platform of this single case study, future larger scale studies are warranted.

Pediatric Autoimmune Encephalitis: Case Series From Two Chinese Tertiary Pediatric Neurology Centers

Background and purpose: We retrospectively analyzed the clinical characteristics of children with autoimmune encephalitis (AE) in two Chinese tertiary pediatric neurology centers. We also compared anti-NMDAR encephalitis with and without co-positive MOG antibody, as well as specific autoantibody-positive AE and autoantibody-negative but probable AE.Methods: A retrospective study of children (0–18 years old) with AE in Peking University First Hospital and Children's Hospital Affiliated to Capital Institute of Pediatrics was carried out from May 2012 to January 2017. Demographics, clinical features, laboratory, and imaging findings, outcome, and co-positivity with MOG antibody were analyzed.Results: A total of 103 children had AE, 89 (86.4%) had anti-NMDAR encephalitis, 2 (1.9%) had anti-LGI1 encephalitis, 1 (0.9%) had anti-CASPR2 encephalitis, and 11 (10.7%) were diagnosed as autoantibody-negative but probable AE. Among the 89 children with anti-NMDAR encephalitis, 35 were males and 54 were females. The follow-up time was 1–3 years. A total of 15 cases (15/89, 16.9%) with anti-NMDAR encephalitis had co-positive MOG antibody (serum or cerebrospinal fluid or both). These patients were more likely to experience relapse later in life (P = 0.014). We had two cases with anti-LGI1 encephalitis, that is, one with sleep disorder onset, and the other one with seizure onset, both of whom recovered after treatment. One case with anti-CASPR2 encephalitis was treated with an antiepileptic drug and fully recovered. There were 11 cases diagnosed as autoantibody-negative but probable AE who had relatively poorer outcome than those with autoantibody-positive AE (15.2%, 14/89). However, the difference was not significant (P = 0.08). Only one 12-year-old girl with NMDAR-antibody AE had ovarian teratoma.Conclusion: Most subjects with AE in our Chinese cohort had anti-NMDAR AE, which had relatively good prognosis. Children with anti-LGI1 or anti-CASPR2 encephalitis were rare and showed good response on immunotherapy. Co-positive MOG antibody was relatively common in anti-NMDAR encephalitis, which was related to high relapse rate. In our study, the prognosis of autoantibody-negative but probable AE seemed worse than that of specific autoantibody-positive AE.

Disrupted AMPA Receptor Function upon Genetic- or Antibody-Mediated Loss of Autism-Associated CASPR2.

Neuropsychiatric disorders share susceptibility genes, suggesting a common origin. One such gene is CNTNAP2 encoding contactin-associated protein 2 (CASPR2), which harbours mutations associated to autism, schizophrenia, and intellectual disability. Antibodies targeting CASPR2 have also been recently described in patients with several neurological disorders, such as neuromyotonia, Morvan's syndrome, and limbic encephalitis. Despite the clear implication of CNTNAP2 and CASPR2 in neuropsychiatric disorders, the pathogenic mechanisms associated with alterations in CASPR2 function are unknown. Here, we show that Caspr2 is expressed in excitatory synapses in the cortex, and that silencing its expression in vitro or in vivo decreases the synaptic expression of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and the amplitude of AMPA receptor-mediated currents. Furthermore, Caspr2 loss of function blocks synaptic scaling in vitro and experience-dependent homoeostatic synaptic plasticity in the visual cortex. Patient CASPR2 antibodies decrease the dendritic levels of Caspr2 and synaptic AMPA receptor trafficking, and perturb excitatory transmission in the visual cortex. These results suggest that mutations in CNTNAP2 may contribute to alterations in AMPA receptor function and homoeostatic plasticity, and indicate that antibodies from anti-CASPR2 encephalitis patients affect cortical excitatory transmission.

Characteristics of Seizure and Antiepileptic Drug Utilization in Outpatients With Autoimmune Encephalitis.

Autoimmune encephalitis (AE) is one kind of encephalitis that associates with specific neuronal antigens. Most patients with AE likely suffer from seizures, but data on the characteristics of seizure and antiepileptic drugs (AEDs) utilization in this patient group remains limited. This study aimed to report the clinical status of seizure and AEDs treatment of patients with AE, and to evaluate the relationship between AEDs discontinuation and seizure outcomes. Patients with acute neurological disorders and anti-N-methyl-D-aspartate receptor (NMDAR), γ-aminobutyric acid B receptor (GABABR), leucine-rich glioma inactivated 1, or contactin-associated protein-like 2 (CASPR2) antibodies were included. As patients withdrew from AEDs, they were divided into the early withdrawal (EW, AEDs used ≤3 months) and late withdrawal (LW, AEDs used >3 months) groups. Seizure remission was defined as having no seizures for at least 1 year after the last time when AEDs were administered. Seizure outcomes were assessed on the basis of remission rate. The factors affecting the outcomes were assessed through Spearman analysis. In total, we enrolled 75 patients (39 patients aged <16 years, male/female = 39/36) for follow-up, which included 67 patients with anti-NMDAR encephalitis, 4 patients with anti-GABABR encephalitis, 2 patients with anti-voltage-gated potassium channel encephalitis, and 2 patients with coexisting antibodies. Among the 34 enrolled patients with anti-NMDAR encephalitis who were withdrawn from AEDs, only 5.8% relapse was reported during the 1-year follow-up, with no significant difference in the percentage of relapse between the EW and LW groups (P = 0.313). Fifteen patients (an average age of 6.8, 14 patients with anti-NMDAR encephalitis and 1 patient with anti-CASPR2 encephalitis) presented seizure remission without any AEDs. Seventy five percent of patients with anti-GABABR antibodies developed refractory seizure. Other risk factors which contributed to refractory seizure and seizure relapse included status epilepticus (P = 0.004) and cortical abnormalities (P = 0.028). Given this retrospective data, patients with AE have a high rate of seizure remission, and the long-term use of AEDs may not be necessary to control the seizure. Moreover, seizures in young patients with anti-NMDAR encephalitis presents self-limited. Patients with anti-GABABR antibody, status epilepticus, and cortical abnormalities are more likely to develop refractory seizure or seizure relapse.

Autoimmune encephalitis with anti-leucine-rich glioma-inactivated 1 or anti-contactin-associated protein-like 2 antibodies (formerly called voltage-gated potassium channel-complex antibodies).

Twenty years since the discovery of voltage-gated potassium channel (VGKC)-related autoimmunity; it is currently known that the antibodies are not directed at the VGKC itself but to two closely associated proteins, anti-leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (Caspr2). Antibodies to LGI1 and Caspr2 give well-described clinical phenotypes. Anti-LGI1 encephalitis patients mostly have limbic symptoms, and anti-Caspr2 patients have variable syndromes with both central and peripheral symptoms. A large group of patients with heterogeneous symptoms are VGKC positive but do not have antibodies against LGI1 or Caspr2. The clinical relevance of VGKC positivity in these 'double-negative' patients is questionable. This review focusses on these three essentially different subgroups. The clinical phenotypes of anti-LGI1 encephalitis and anti-Caspr2 encephalitis have been described in more detail including data on treatment and long-term follow-up. A specific human leukocyte antigen (HLA) association was found in nontumor anti-LGI1 encephalitis, but not clearly in those with tumors. There has been increasing interest in the VGKC patients without LGI1/Caspr2 antibodies questioning its relevance in clinical practice. Anti-LGI1 encephalitis and anti-Caspr2 encephalitis are separate clinical entities. Early recognition and treatment is necessary and rewarding. The term VGKC-complex antibodies, lumping patients with anti-LGI1, anti-Caspr2 antibodies or lacking both, should be considered obsolete.

Anti-contactin-associated protein-2 encephalitis: relevance of antibody titres, presentation and outcome.

To clarify the relevance of titres of IgG antibodies against contactin-associated protein-2 (CASPR2) in diagnosing anti-CASPR2 encephalitis and to describe features and outcomes. This was a retrospective analysis of 64 patients with CASPR2 antibodies, categorized independently as 'autoimmune encephalitis' or 'other disease'. Logistic regression methods were performed to identify potential predictors of 'autoimmune encephalitis' in addition to CASPR2 antibodies. An upfront CASPR2 antibody serum titre cut-off at ≥1:200 had a diagnostic sensitivity of 85% and a specificity of 81%. Logistic regression analyses indicated that, in addition to titre, encephalitic magnetic resonance imaging (MRI) was a significant predictor of 'autoimmune encephalitis' (Nagelkerke's R2 = 0.81, P < 0.001) with high sensitivity (84%) and very high specificity (100%). Patients with CASPR2 antibodies and an estimated probability of >70% of having anti-CASPR2 encephalitis (n = 22) had limbic encephalitis (n = 18, one patient plus ataxia), Morvan syndrome (n = 2) or a hyperkinetic movement disorder (n = 2). Median modified Rankin score (mRS) at diagnosis was 3 (range 1-4). Twenty patients were male; median age was 64 (range 54-75) years; 5/15 patients with cerebrospinal fluid data had intrathecal CASPR2 antibody synthesis, and 12/19 with follow-ups >3 months (median 12 months, range 4-43 months) improved by ≥1 mRS point resulting in a median mRS of 2 (range 0-6; one death; all but one having received immunotherapy); and 2/15 patients with follow-up MRI developed hippocampal atrophy. Only higher CASPR2 serum antibody titres indicate anti-CASPR2 encephalitis, and diagnostic accuracy increases if MRI findings are considered. Anti-CASPR2 encephalitis has characteristic features and a favourable outcome with immunotherapy.