Autoimmune encephalitis: what the radiologist needs to know.

Autoimmune encephalitis is a relatively novel nosological entity characterized by an immune-mediated damage of the central nervous system. While originally described as a paraneoplastic inflammatory phenomenon affecting limbic structures, numerous instances of non-paraneoplastic pathogenesis, as well as extra-limbic involvement, have been characterized. Given the wide spectrum of insidious clinical presentations ranging from cognitive impairment to psychiatric symptoms or seizures, it is crucial to raise awareness about this disease category. In fact, an early diagnosis can be dramatically beneficial for the prognosis both to achieve an early therapeutic intervention and to detect a potential underlying malignancy. In this scenario, the radiologist can be the first to pose the hypothesis of autoimmune encephalitis and refer the patient to a comprehensive diagnostic work-up - including clinical, serological, and neurophysiological assessments.In this article, we illustrate the main radiological characteristics of autoimmune encephalitis and its subtypes, including the typical limbic presentation, the features of extra-limbic involvement, and also peculiar imaging findings. In addition, we review the most relevant alternative diagnoses that should be considered, ranging from other encephalitides to neoplasms, vascular conditions, and post-seizure alterations. Finally, we discuss the most appropriate imaging diagnostic work-up, also proposing a suggested MRI protocol.

Seizures in anti-Hu-associated extra-limbic encephalitis: Characterization of a unique disease manifestation.

Anti-Hu-associated neurologic autoimmunity most often occurs in the context of small cell lung cancer and typically presents with peripheral neuropathy, cerebellar ataxia, and/or limbic encephalitis. Extra-limbic encephalitis causing seizures is a rare disease manifestation, with only sparse reports in the literature. Herein we present a patient with seizures in anti-Hu-associated extra-limbic encephalitis, and review the literature for other cases to more fully characterize this entity. Among 27 patients we identified, the median age was 46 years (range: 2-69 years) and 18 of 27 (67%) were female. Focal motor seizures were most common, followed by ictal expressive speech difficulty. Seizure semiologies along with neuroimaging findings most frequently suggested the involvement of the peri-Rolandic cortex, more anterior frontal operculum, and insula, although other cortical regions were rarely affected as well. In contrast to other classical paraneoplastic neurologic syndromes, good response to treatment with attainment of seizure-free survival was often reported, although over one-third still died. A propensity for chronic seizures among children indicated the potential to develop autoimmune-associated epilepsy. The predilection for certain extra-limbic regions, as well as the possibility of good response to treatment, may reflect unique disease mechanisms that would benefit from further study.

Diagnostic challenges in patients with temporal lobe seizures and features of autoimmune limbic encephalitis.

BACKGROUND AND PURPOSE: Consensus criteria for autoimmune limbic encephalitis (ALE) allow for a diagnosis even without neuronal antibodies (Abs), but it remains unclear which clinical features should prompt neuronal Ab screening in temporal lobe epilepsy patients. The aim of the study was to investigate whether patients with temporal lobe seizures associated with additional symptoms or signs of limbic involvement may harbor neuronal Abs, and which clinical features should prompt neuronal Ab screening in these patients. METHODS: We identified 47 patients from a tertiary epilepsy center with mediotemporal lobe seizures and additional features suggestive of limbic involvement, including either memory deficits, psychiatric symptoms, mediotemporal magnetic resonance imaging (MRI) hyperintensities or inflammatory cerebrospinal fluid (CSF). Neuronal Ab testing was carried out at two independent reference laboratories (Bielefeld-Bethel, Germany, and Barcelona, Spain). All brain MRI scans were assessed by two reviewers independently. RESULTS: Temporal lobe seizures were accompanied by memory deficits in 35/46 (76%), psychiatric symptoms in 27/42 (64%), and both in 19/42 patients (45%). Limbic T2/fluid-attenuated inversion recovery signal hyperintensities were found in 26/46 patients (57%; unilateral: n = 22, bilateral: n = 4). Standard CSF studies were abnormal in 2/37 patients (5%). Neuronal Abs were confirmed in serum and/or CSF in 8/47 patients (17%) and were directed against neuronal cell-surface targets (leucine-rich glioma inactivated protein 1: n = 1, contactin-associated protein-2: n = 1, undetermined target: n = 3) or glutamic acid decarboxylase in its 65-kD isoform (n = 3, all with high titers). Compared to Ab-negative patients, those who harbored neuronal Abs were more likely to have uni- or bilateral mediotemporal MRI changes (8/8, 100% vs. 18/38, 47%; p = 0.01, Fisher's exact test). CONCLUSIONS: In patients with temporal lobe seizures and additional limbic signs, 17% had neuronal Abs affirming ALE diagnosis. Mediotemporal MRI changes were found in all Ab-positive cases and had a positive likelihood ratio of 2.11 (95% confidence interval 1.51-2.95).

Persistent hiccup as one of the initial symptoms of leucine-rich glioma-inactivated-1 encephalitis: a case report.

BACKGROUND: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis, an autoimmune disorder, is characterized by faciobrachial dystonic seizures, epilepsy, memory deficits and altered mental status while hiccup is not commonly found in patients. CASE PRESENTATION: A 62-year-old male was presented with slurred speech, abnormal gait, faciobrachial dystonic seizures and impaired cognition. Besides, the hiccup was one of the initial symptoms. His brain magnetic resonance images (MRI) revealed multiple lesions with left caudate nucleus, putamen, insula and left hippocampus involvement. Because a diagnosis of antibody-related limbic encephalitis was suspected, studies including an autoimmune profile were done by cell-based assays. After anti-LGI1 antibodies were detected in both cerebrospinal fluid and serology, pulse methylprednisolone and intravenous immunoglobulin were started and hence hiccups disappeared along with other symptoms. CONCLUSIONS: Clinicians should be aware that persistent hiccups might be one of the initial manifestations of LGI1 subtype of voltage-gated potassium channel complex antibody associated autoimmune encephalitis.

Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis.

Limbic encephalitis with antibodies against adenylate kinase 5 (AK5) has been difficult to characterize because of its rarity. In this study, we identified 10 new cases and reviewed 16 previously reported patients, investigating clinical features, IgG subclasses, human leucocyte antigen and CSF proteomic profiles. Patients with anti-AK5 limbic encephalitis were mostly male (20/26, 76.9%) with a median age of 66 years (range 48-94). The predominant symptom was severe episodic amnesia in all patients, and this was frequently associated with depression (17/25, 68.0%). Weight loss, asthenia and anorexia were also highly characteristic, being present in 11/25 (44.0%) patients. Although epilepsy was always lacking at disease onset, seizures developed later in a subset of patients (4/25, 16.0%). All patients presented CSF abnormalities, such as pleocytosis (18/25, 72.0%), oligoclonal bands (18/25, 72.0%) and increased Tau (11/14, 78.6%). Temporal lobe hyperintensities were almost always present at disease onset (23/26, 88.5%), evolving nearly invariably towards severe atrophy in subsequent MRIs (17/19, 89.5%). This finding was in line with a poor response to immunotherapy, with only 5/25 (20.0%) patients responding. IgG1 was the predominant subclass, being the most frequently detected and the one with the highest titres in nine CSF-serum paired samples. A temporal biopsy from one of our new cases showed massive lymphocytic infiltrates dominated by both CD4+ and CT8+ T cells, intense granzyme B expression and abundant macrophages/microglia. Human leucocyte antigen (HLA) analysis in 11 patients showed a striking association with HLA-B*08:01 [7/11, 63.6%; odds ratio (OR) = 13.4, 95% confidence interval (CI): 3.8-47.4], C*07:01 (8/11, 72.7%; OR = 11.0, 95% CI: 2.9-42.5), DRB1*03:01 (8/11, 72.7%; OR = 14.4, 95% CI: 3.7-55.7), DQB1*02:01 (8/11, 72.7%; OR = 13.5, 95% CI: 3.5-52.0) and DQA1*05:01 (8/11, 72.7%; OR = 14.4, 95% CI: 3.7-55.7) alleles, which formed the extended haplotype B8-C7-DR3-DQ2 in 6/11 (54.5%) patients (OR = 16.5, 95% CI: 4.8-57.1). Finally, we compared the CSF proteomic profile of five anti-AK5 patients with that of 40 control subjects and 10 cases with other more common non-paraneoplastic limbic encephalitis (five with antibodies against leucine-rich glioma inactivated 1 and five against contactin-associated protein-like 2), as well as 10 cases with paraneoplastic neurological syndromes (five with antibodies against Yo and five against Ma2). These comparisons revealed 31 and seven significantly upregulated proteins in anti-AK5 limbic encephalitis, respectively mapping to apoptosis pathways and innate/adaptive immune responses. These findings suggest that the clinical manifestations of anti-AK5 limbic encephalitis result from a distinct T cell-mediated pathogenesis, with major cytotoxicity-induced apoptosis leading to a prompt and aggressive neuronal loss, likely explaining the poor prognosis and response to immunotherapy.

Autoimmune and limbic encephalitis: case series with some atypical variables in clinical practice.

Autoimmune and limbic encephalitides are still rare diseases characterized by rapid diagnostics and treatment development in recent years. The incidence of anti-N-methyl-D- aspartate receptor [NMDAR] encephalitis is about 1.5 per million person per year, and the incidence of paraneoplastic neurological syndromes [PNS] including limbic encephalitis [LE] is about 1.22 per 100 000 person per year (Vogrig et al. J Neurol 267:26-35, 1; Dalmau et al. Ann Neurol 61:25-36, 2). The diagnostic criteria of anti-NMDAR encephalitis are already well established (Zuliani et al. Neurol Sci 40:2017-2030, 10). We provide immunological and clinical characteristics of anti-NMDAR encephalitis case series emphasizing unusual association with colon tumour in one case and complete recovery in two cases. Then we report two cases of onconeural and cell surface antibody negative limbic encephalitis [LE] associated with tumours, seizures, cognitive and behavioural changes resulting in severe cerebellar syndrome and fatal outcome. The clinical characteristics and results of selected paraclinical examinations as electroencephalography [EEG], magnetic resonance imaging [MRI] and cerebrospinal fluid [CSF] analysis are reviewed.

What Is Different about Teratoma-Associated Anti-LGI1 Encephalitis? A Long-Term Clinical and Neuroimaging Case Series.

INTRODUCTION: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is clinically heterogeneous, especially at presentation, and though it is sometimes found in association with tumor, this is by no means the rule. METHODS: Clinical data for 10 patients with anti-LGI1 encephalitis were collected including one case with teratoma and nine cases without and compared for clinical characteristics. Microscopic pathological examination and immunohistochemical assay of the LGI1 antibody were performed on teratoma tissue obtained by laparoscopic oophorocystectomy. RESULTS: In our teratoma-associated anti-LGI1 encephalitis case, teratoma pathology was characterized by mostly thyroid tissue and immunohistochemical assay confirmed positive nuclear staining of LGI1 in some tumor cells. The anti-LGl1 patient with teratoma was similar to the non-teratoma cases in many ways: age at onset (average 47.3 in non-teratoma cases); percent presenting with rapidly progressive dementia (67% of non-teratoma cases) and psychiatric symptoms (33%); hyponatremia (78%); normal cerebrospinal fluid results except for positive LGI1 antibody (78%); bilateral hippocampal hyperintensity on magnetic resonance imaging (44%); diffuse slow waves on electroencephalography (33%); good response to immunotherapy (67%); and mild residual cognitive deficit (22%). Her chronic anxiety and presentation with status epilepticus were the biggest differences compared with the non-teratoma cases. CONCLUSION: In our series, anti-LGI1 encephalitis included common clinical features in our series: rapidly progressive dementia, faciobrachial dystonic seizures, behavioral disorders, hyponatremia, hippocampal hyperintensity on magnetic resonance imaging, and residual cognitive deficit. We observed some differences (chronic anxiety and status epilepticus) in our case with teratoma, but a larger accumulation of cases is needed to improve our knowledge base.

Determinants of cognition in autoimmune limbic encephalitis-A retrospective cohort study.

Autoimmune limbic encephalitis (ALE) is the most common type of autoimmune encephalitis (AIE). Subacute memory disturbance, temporal lobe seizures, and psychiatric symptoms are clinical hallmarks of the disease. However, little is known on the factors contributing to cognitive functioning in ALE. Hence, we here investigate major determinants of cognitive functioning in ALE. In a retrospective analysis of 102 patients with ALE, we first compared verbal learning capacity, nonverbal learning capacity, and attentional and executive functioning by absence or presence of different types of neural autoantibodies (AABs). Subsequently we established three linear regression models including 63, 38, and 61 patients, respectively to investigate how cognitive functioning in these domains may depend on common markers of ALE such as intrathecal inflammation, blood-cerebrospinal fluid (CSF)-barrier function, mesiotemporal epileptiform discharges and slowing, determined by electroencephalography (EEG) and structural mesiotemporal changes, measured with magnetic resonance imaging (MRI). We also accounted for possible effects of cancer- and immunotherapy and other centrally effective medication. There was no effect of AAB status on cognitive functioning. Although the regression models could not predict verbal and nonverbal learning capacity, structural mesiotemporal neural network alterations on T2-/fluid attenuated inversion recovery (FLAIR)-signal-weighted MRI and mesiotemporal epileptiform discharges or slowing on EEG exerted a significant impact on memory functions. In contrast, the regression model significantly predicted attentional and executive functioning with CSF white blood cell count and centrally effective medication being significant determinants. In this cohort, cognitive functioning in ALE does not depend on the AAB status. Common markers of ALE cannot predict memory functioning that only partially depends on structural and functional alterations of mesiotemporal neural networks. Common markers of ALE significantly predict attentional and executive functioning that is significantly related to centrally effective medication and CSF white blood cell count, which may point toward inflammation affecting brain regions beyond the limbic system.

ASL MRI and 18F-FDG-PET in autoimmune limbic encephalitis: clues from two paradigmatic cases.

BACKGROUND: Autoimmune limbic encephalitis (LE) is a neurological condition characterized by seizures and cognitive dysfunction. Fluorine-18 fluorodeoxyglucose (18F-FDG-PET) has recently proved to be an important diagnostic tool in this condition since it may highlight brain metabolism abnormalities in a very early stage of the disease. Two main 18F-FDG-PET patterns have been described: the mixed hypermetabolic/hypometabolic and the neurodegenerative one. Arterial spin labeling (ASL) is an MRI technique showing brain perfusion, rarely used in autoimmune neurological conditions. The aim of the present study was to study patients with LE with both techniques, in order to compare their results. METHODS: Two patients with LE underwent to 18F-FDG-PET and ASL MRI scans using the pseudo-continuous arterial spin labeling (PCASL) technique. Areas of altered perfusion and metabolism were analyzed by visual inspection, and findings were compared between the two techniques. RESULTS: In the first patient, a relapsing LGI-1 LE, right hippocampal hypermetabolism was detected by 18F-FDG-PET (mixed hypermetabolic/hypometabolic pattern), while ASL MRI showed right hippocampal increased perfusion. In the second patient, a seronegative LE, 18F-FDG-PET scan detected a left hemispheric hypoperfusion (neurodegenerative pattern) and ASL MRI yielded similar results. The two 18F-FDG-PET patterns of altered metabolism were similarly detected by ASL imaging. CONCLUSION: ASL and 18F-FDG-PET findings are strongly concordant in LE. ASL imaging was able to detect the two main 18F-FDG-PET patterns previously described in patients with LE.

Structural network topology in limbic encephalitis is associated with amygdala enlargement, memory performance and serostatus.

Limbic encephalitis (LE) forms a spectrum of autoimmune diseases involving temporal lobe epilepsy and memory impairment. Imaging features of LE are known to depend on the associated antibody and to occur on the brain network level. However, first studies investigating brain networks in LE have either focused on one distinct antibody subgroup or on distinct anatomical regions. In this study, brain graphs of 17 LE patients with autoantibodies against glutamic acid decarboxylase 65 (GAD-LE), four LE patients with autoantibodies against leucine-rich glioma-inactivated 1, five LE patients with autoantibodies against contactin-associated protein-like 2, 26 age- and gender-matched healthy control subjects, and 20 epilepsy control patients with hippocampal sclerosis were constructed based on T1-weighted structural magnetic resonance imaging scans and diffusion tensor imaging. GAD-LE showed significantly altered global network topology in terms of integration and segregation as compared to healthy controls and patients with hippocampal sclerosis (P < .01, analysis of variance with Tukey-Kramer post hoc tests). Linear regression linked global network measures with amygdala volume and verbal memory performance (P < .05). Alterations of local network topology show serotype dependence in hippocampus, amygdala, insula, and various cortical regions. Our findings reveal serotype-dependent patterns of structural connectivity and prove the relevance of in silico network measures on clinical grounds.

CD19+ B-cells in autoantibody-negative limbic encephalitis.

PURPOSE: Flow cytometry helps to elucidate the cellular immune repertoire's mechanisms in patients with temporal lobe epilepsy (TLE) due to limbic encephalitis (LE) subcategories and carries potential significance for subtype-specific treatment. METHODS: We enrolled 62 patients with TLE due to LE associated with no autoantibodies (n = 40), neural autoantibodies (n = 22), as well as autoantibodies against intracellular antigens (n = 15/22). All patients underwent neuropsychological testing, brain magnetic resonance imaging (MRI), electroencephalography (EEG) recordings, and peripheral blood (PB) and cerebrospinal fluid (CSF) investigations including flow cytometry. RESULTS: CD19+ B-cells were increased in the PB and CSF of patients with antibody-negative LE compared with those associated with antibodies against intracellular antigens (Kruskal-Wallis one way analysis of variance (ANOVA) on ranks with Dunn's test, p < 0.05). There were no differences in CD138+ B-cells, CD4+ T-cells, human leukocyte antigen - DR isotype (HLA-DR+) CD4+ T-cells, CD8+ T-cells, and HLA-DR+ CD8+ T-cells in the CSF between groups with LE. The blood-brain barrier is more often impaired in patients with antibody-negative LE than in LE with antibodies against intracellular antigens (chi-square test, p < 0.05). In addition, we detected no correlations between immune cell subsets and clinical or paraclinical parameters in patients with antibody-negative and intracellular antibody-positive LE. CONCLUSIONS: The increase of CD19+ B-cells in the CSF and frequent signs of dysfunctional blood-brain barrier in patients with antibody-negative rather than intracellular antibody-positive LE suggest that CD19+ B-cells play a role in antibody-negative encephalitis although their pathogenic role in the central nervous system (CNS) immunity because of missing correlations between immune cells and clinical and paraclinical parameters remains unknown. Further studies are required to evaluate the usefulness of these B-cells as a biomarker for the stratification of treatment strategies.

Low CSF CD4/CD8+ T-cell proportions are associated with blood-CSF barrier dysfunction in limbic encephalitis.

PURPOSE: Investigating immune cells in autoimmune limbic encephalitis (LE) will contribute to our understanding of its pathophysiology and may help to develop appropriate therapies. The aim of the present study was to analyze immune cells to reveal underlying immune signatures in patients with temporal lobe epilepsy (TLE) with LE. METHODS: We investigated 68 patients with TLE with LE compared with 7 control patients with TLE with no signs of LE screened from 154 patients with suspected LE. From the patients with TLE-LE, we differentiated early seizure onset (<20 years, n = 9) and late seizure onset group (≥20 years, n = 59) of patients. Patients underwent neuropsychological assessment, electroencephalography (EEG), brain magnetic resonance imaging (MRI), and peripheral blood (PB) and cerebrospinal fluid (CSF) analysis including flow cytometry. RESULTS: We identified a higher CD4/8+ T-cell ratio in the PB in all patients with TLE-LE and in patients with late-onset TLE-LE each compared with controls (Kruskal-Wallis one-way ANOVA (analysis of variance) with Dunn's test, p < 0.05). Moreover, a lower CD4/CD8+ T-cell ratio is detected in all patients with TLE-LE with blood-CSF barrier dysfunction, unlike in those with none (Kruskal-Wallis one-way ANOVA with Dunn's test, p < 0.05). CONCLUSIONS: These findings suggest that the proportion of CD4+ and CD8+ T-cells in the CSF of patients with LE associated with blood-CSF barrier dysfunction plays a potential role in CNS (central nervous system) inflammation in these patients. Thus, flow cytometry as a methodology reveals novel insights into LE's genesis and symptomatology. The CD4/8+ T-cell ratio in PB as a biomarker for LE requires further investigation.

Characterizing memory loss in patients with autoimmune limbic encephalitis hippocampal lesions.

Since the publication of Scoville and Milner's (1957) seminal paper, the precise functional role played by the hippocampus in support of human memory has been fiercely debated. For instance, the single question of whether the hippocampus plays a time-limited or an indelible role in the recollection of personal memories led to a deep and tenacious schism within the field. Similar polarizations arose between those who debated the precise nature of the role played by the hippocampus in support of semantic relative to episodic memories and in recall/recollection relative to familiarity-based recognition. At the epicenter of these divisions lies conflicting neuropsychological findings. These differences likely arise due to the consistent use of heterogeneous patient populations to adjudicate between these positions. Here we utilized traditional neuropsychological measures in a homogenous patient population with a highly discrete hippocampal lesion (i.e., VGKCC-Ab related autoimmune limbic encephalitis patients). We observed consistent impairment of recent episodic memories, a present but less striking impairment of remote episodic memories, preservation of personal semantic memory, and recall but not recognition memory deficits. We conclude that this increasingly well-characterized patient group may represent an important homogeneous population in which the functional role played by the hippocampus may be more precisely delineated.

Hippocampal network abnormalities explain amnesia after VGKCC-Ab related autoimmune limbic encephalitis.

OBJECTIVE: Limbic encephalitis associated with antibodies to components of the voltage-gated potassium channel complex (VGKCC-Ab-LE) often leads to hippocampal atrophy and persistent memory impairment. Its long-term impact on regions beyond the hippocampus, and the relationship between brain damage and cognitive outcome, are poorly understood. We investigated the nature of structural and functional brain abnormalities following VGKCC-Ab-LE and its role in residual memory impairment. METHOD: A cross-sectional group study was conducted. Twenty-four VGKCC-Ab-LE patients (20 male, 4 female; mean (SD) age 63.86 (11.31) years) were recruited post-acutely along with age- and sex-matched healthy controls for neuropsychological assessment, structural MRI and resting-state functional MRI (rs-fMRI). Structural abnormalities were determined using volumetry and voxel-based morphometry; rs-fMRI data were analysed to investigate hippocampal functional connectivity (FC). Associations of memory performance with neuroimaging measures were examined. RESULTS: Patients showed selective memory impairment. Structural analyses revealed focal hippocampal atrophy within the medial temporal lobes, correlative atrophy in the mediodorsal thalamus, and additional volume reduction in the posteromedial cortex. There was no association between regional volumes and memory performance. Instead, patients demonstrated reduced posteromedial cortico-hippocampal and inter-hippocampal FC, which correlated with memory scores (r = 0.553; r = 0.582, respectively). The latter declined as a function of time since the acute illness (r = -0.531). CONCLUSION: VGKCC-Ab-LE results in persistent isolated memory impairment. Patients have hippocampal atrophy with further reduced mediodorsal thalamic and posteromedial cortical volumes. Crucially, reduced FC of remaining hippocampal tissue correlates more closely with memory function than does regional atrophy.

Conventional brain MRI features distinguishing limbic encephalitis from mesial temporal glioma.

PURPOSE: Radiological hallmark of autoimmune limbic encephalitis (LE) is a hyperintense signal in MRI T2-weighted images of mesial temporal structures. We aimed to identify conventional magnetic resonance imaging (MRI) features that can help distinguish LE from temporal glioma. METHODS: Brain MRIs of 25 patients affected by antibody-positive autoimmune LE, 24 patients affected by temporal glioma (tumor group), and 5 negative controls were retrospectively blindly evaluated in random order. RESULTS: Ten brain MRIs from the LE group were correctly recognized; one additional patient with mesial temporal hyperintensity with anti-AK5 abs LE was wrongly diagnosed as having a tumor. The brain MRIs of the remaining 14 of the 25 patients with LE were judged negative or, in three cases, showed features not typical for LE. In the tumor group, all MRIs showed pathological alterations diagnosed as tumors in 22/24 cases and as LE in two (2/22, 9%). Unilateral lesions were more common in tumors than in neuroradiologically abnormal LE (96% vs. 18%, p < 0.001). T2/FLAIR hyperintensity of the parahippocampal gyrus was associated more with tumor than with LE (71% vs. 18%) (p = 0,009), as T2/FLAIR hyperintensity of extralimbic structures (p = 0.015), edema (p = 0.041), and mass effect (p = 0.015). Maintenance of gray/white matter distinction was strongly associated with LE (91% vs. 17%, p < 0.001). CONCLUSION: Conventional brain MRI is a fundamental tool in the differential diagnosis between LE and glioma. Bilateral involvement and maintenance of gray/white matter distinction at the cortical/subcortical interface are highly suggestive of LE.

Three cases of antibody-LGI1 limbic encephalitis and review of literature.

PURPOSE: Antibody-LGI1 limbic encephalitis (LGI1-Ab LE) is an anti-neuronal surface antigen-related autoimmune encephalitis. we report three cases of LGI1-Ab LE, describe the characteristics of clinical manifestation, course of evolution, imaging manifestation and treatment outcomes. METHODS: Data from patients diagnosed with LGI1-Ab LE in the Second Hospital, Hebei Medical University, from June 2016 to July 2017, were retrospectively collected and analyzed. We followed up the patients for 90 days. RESULTS: Two of the three patients were females, the average age of onset is 53 years old. Epilepsy is the most common clinical manifestations, and one of patients developed faciobrachial dystonic seizures (FBDS), which was recently described as a characteristic feature of LGI1-Ab LE. All patients had cognitive impairment in different degrees and abnormal signal of hippocampus in cranial MRI. All serum LGI1 antibodies were positive, whereas one LGI1 antibodies of CSF were negative. All patients accepted first-line immune therapy and had a good outcome. CONCLUSION: LGI1-Ab LE, which is an autoimmune disease, is rare clinically and mostly nonparaneoplastic. We suggest that LGI1-Ab LE be considered in any patient with acute or subacute onset, cognitive dysfunction , various types of seizures, accompanied by mental disorders and hyponatremia, MR showed the involvement of the limbic system. It is necessary to have LE-related antibodies tested. Early immunotherapy can significantly improve the patient's overall prognosis. At the same time, we should also pay attention to the possibility of potential tumors.

Deciding what is possible and impossible following hippocampal damage in humans.

There is currently much debate about whether the precise role of the hippocampus in scene processing is predominantly constructive, perceptual, or mnemonic. Here, we developed a novel experimental paradigm designed to control for general perceptual and mnemonic demands, thus enabling us to specifically vary the requirement for constructive processing. We tested the ability of patients with selective bilateral hippocampal damage and matched control participants to detect either semantic (e.g., an elephant with butterflies for ears) or constructive (e.g., an endless staircase) violations in realistic images of scenes. Thus, scenes could be semantically or constructively 'possible' or 'impossible'. Importantly, general perceptual and memory requirements were similar for both types of scene. We found that the patients performed comparably to control participants when deciding whether scenes were semantically possible or impossible, but were selectively impaired at judging if scenes were constructively possible or impossible. Post-task debriefing indicated that control participants constructed flexible mental representations of the scenes in order to make constructive judgements, whereas the patients were more constrained and typically focused on specific fragments of the scenes, with little indication of having constructed internal scene models. These results suggest that one contribution the hippocampus makes to scene processing is to construct internal representations of spatially coherent scenes, which may be vital for modelling the world during both perception and memory recall. © 2016 The Authors. Hippocampus Published by Wiley Periodicals, Inc.

Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study.

BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. METHODS: We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. RESULTS: A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. CONCLUSIONS: Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.