Structural and Functional Changes in Non-Paraneoplastic Autoimmune Retinopathy.

BACKGROUND: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. METHODS: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. RESULTS: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0-18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. CONCLUSIONS: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure.

Favorable Outcomes in a Case of Non-paraneoplastic DNER Ataxia Treated with Immunotherapy.

Anti-DNER antibody is associated with paraneoplastic cerebellar degeneration (PCD) and Hodgkin's disease (HD). However, recent studies reported cases absence of HD and that non-tumor anti-DNER antibody-associated ataxia was not well characterized. We present a case of acute cerebellar ataxia and nystagmus with detected anti-DNER antibody. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy. High titer of anti-DNER antibody was detected in CSF and serum. Positron emission tomography (PET) scanning was unremarkable at a 10-month follow up. The patient improved significantly after immunosuppressive therapy with intravenous steroids, immunoglobulin followed by rituximab. Our study suggest that the presence of such anti-neuronal antibodies might not come along with malignancy and that early onset non-tumor patients are more likely to have a better outcome after immunotherapy. Early diagnosis and timely immunosuppressive therapy may prove beneficial for these patients.

Comparison of Clinical and Immunological Features of Para- and Non-Paraneoplastic Autoimmune Retinopathy in Chinese - A Series of 48 Cases.

PURPOSE: To characterize and compare clinical and immunological features of para(p)-autoimmune retinopathy (AIR) and non-para(np)-AIR and to assess the clinical significance of the presence of serum anti-retinal antibodies (ARAs). METHODS: We retrospectively reviewed 48 Chinese patients with p-AIR or np-AIR who took comprehensive ophthalmic examinations and lab tests of the presence of serum ARAs. RESULTS: p-AIR patients differed from np-AIR patients in terms of disease progression, ocular inflammation, findings of OCT, FFA, and presence of ARAs. No significant difference was found in the band number of serum ARAs between AIR patients and healthy controls. The prevalence of antibodies to recoverin and ɑ-enolase in the sera of p-AIR was significantly higher than that of the healthy individuals. CONCLUSION: While having many similar clinical signs, patients with p-AIR or np-AIR nevertheless displayed unique characteristics. Detection of ARAs subtypes, rather than their quantity, may be helpful in evaluating the conditions in the verified instances.

Intrathecal Rituximab as a Rescue Therapy in Refractory Pure CSF Positive, Non-Teratomatous Type Anti-NMDAR Encephalitis.

NMDAR antibody encephalitis is the most common autoimmune encephalitis characterized by a myriad of neuropsychiatric symptoms. It predominantly affects females and is associated with ovarian teratoma (58%). Nineteen percent do not respond to treatment and are left with serious neurological deficits. A subset of NMDAR encephalitis with antibody positivity in CSF alone without ovarian teratoma is often found to be refractory to treatment. We name them Pure CSF positive, non-teratomatous type anti-NMDAR encephalitis . We report two such cases who responded to intrathecal rituximab, to highlight a novel treatment as a rescue therapy to prevent long-term disability and improve clinical outcomes.

Neuronal and Neuroaxonal Damage Cerebrospinal Fluid Biomarkers in Autoimmune Encephalitis Associated or Not with the Presence of Tumor.

The aim of this study was to evaluate the association of neuronal damage biomarkers (neurofilament light chain (NFL) and total tau protein (T-tau)) in the CSF of patients with autoimmune encephalitis (AE) with the presence of an underlying malignancy and to determine correlations with patient characteristics. The study comprised 21 patients with encephalitis associated with antibodies against intracellular (n = 11) and surface/synaptic antigens (extracellular, n = 10) and non-inflammatory disease controls (n = 10). Patients with AE associated with intracellular antigens had increased CSF-NFL (p = 0.003) but not T-tau levels compared to controls. When adjusted for age, CSF-NFL but not CSF-T-tau was higher in patients with encephalitis associated with intracellular antigens as compared to those with encephalitis associated with extracellular antigens (p = 0.032). Total tau and NFL levels were not significantly altered in patients with encephalitis associated with extracellular antigens compared to controls. NFL in the total cohort correlated with neurological signs of cerebellar dysfunction, peripheral neuropathy, presence of CV2 positivity, presence of an underlying tumor and a more detrimental clinical outcome. AE patients with abnormal MRI findings displayed higher NFL levels compared to those without, albeit with no statistical significance (p = 0.07). Using receiver operating characteristic curve analysis, CSF-NFL levels with a cut-off value of 969 pg/mL had a sensitivity and specificity of 100% and 76.19%, respectively, regarding the detection of underlying malignancies. Our findings suggest that neuronal integrity is preserved in autoimmune encephalitis associated with extracellular antigens and without the presence of tumor. However, highly increased NFL is observed in AE associated with intracellular antigens and presence of an underlying tumor. CSF-NFL could potentially be used as a diagnostic biomarker of underlying malignancies in the clinical setting of AE.

Autoimmune retinopathy: clinical, electrophysiological, and immunological features in nine patients with long-term follow-up.

PURPOSE: We aim to report on the clinical, imaging, immunological, and electrophysiological features of patients with autoimmune retinopathy (AIR) with long-term follow-up. METHODS: Single-center, retrospective study of a consecutive group of AIR patients treated in a tertiary academic medical center. RESULTS: Included were nine patients with a mean ± SD age at presentation of 65 ± 13 years and a median follow-up of 63 months (range 18-120). Five patients were known to have cancer. Median interval between onset of ocular symptoms and diagnosis of AIR was 36 months. Mean baseline and final LogMAR visual acuity were 0.72 ± 0.9 and 1.1 ± 1.2, respectively (p = 0.17). The most common funduscopic findings included optic atrophy and bone-spicule-like pigmentation. Thinning of the nerve fiber layer was the most frequent optical coherence tomographic abnormality. Electroretinographic (ERG) recordings demonstrated variably reduced cone- and rod-derived amplitudes in the majority of eyes at presentation. The most commonly detected anti-retinal antibody was anti-α-enolase. Treatment included immunomodulatory therapy and plasmapheresis. ERG tests showed stability in 64% of eyes throughout the treatment period. CONCLUSION: This study highlights the importance of maintaining a high index of suspicion of AIR, particularly in late middle-aged and elderly patients with "unexplained" visual loss, in light of the non-specific posterior segment signs and the inconsistency of the routinely used ancillary tests.

Rituximab Monotherapy versus Rituximab and Bortezomib Combination Therapy for Treatment of Non-paraneoplastic Autoimmune Retinopathy.

Purpose: To study whether rituximab and bortezomib combination therapy is more effective than rituximab monotherapy in the treatment of non-paraneoplastic autoimmune retinopathy (npAIR). Methods: Retrospective case series involving six patients with npAIR, taking either rituximab and bortezomib combination therapy (three cases) or rituximab monotherapy (one case and two historical patients). Results: Patients on both treatment regimens showed stability in most of the visual function parameters during the one year of follow-up. Combination therapy resulted in improvement of scotopic combined rod and cone a-wave and b-wave amplitudes in all eyes where they were available (four eyes); however, rituximab monotherapy resulted in only two eyes with stable scotopic combined rod and cone a-wave and b-wave amplitudes, while four eyes showed a decrease in both a- and b-wave amplitudes. The average improvement in b-wave amplitude (50.7% ± 29.4% [range, 25-90%]) was higher than the average improvement in a-wave amplitude (35.7% ± 9.74 [range, 25-63%]). No severe adverse effects were reported. Conclusion: Rituximab and bortezomib combination therapy may not be more effective than rituximab monotherapy in npAIR patients for most of the visual function parameters; however, this combination therapy may be more effective in improving scotopic combined rod and cone a- and b-wave amplitudes. This may indicate the higher efficacy of combination therapy when there is involvement of the inner retina.

Non-paraneoplastic autoimmune retinopathy that developed in fellow eye 10 years after onset in first eye: a case report.

BACKGROUND: Evidence-based criteria for the treatment of autoimmune retinopathy (AIR) have not been established. The pathology and clinical features of each antibody causing AIR, and its long-term course are still undetermined. We report our findings in a case of non-paraneoplastic AIR (npAIR) that developed in the fellow eye 10 years after the onset in the first eye. CASE PRESENTATION: Our patient had photophobia in both eyes and a rapidly progressing visual field defect in his right eye at the initial examination. He was diagnosed with non-paraneoplastic AIR based on the clinical findings and immunoblot analyses for anti-retinal antibodies, and he was treated with steroids. Ten years later, a visual field defect developed in the fellow eye, and a diagnosis of npAIR was made. Immunoblot analyses were positive for anti-α-enolase antibodies. He was treated with steroids, immunosuppressants, and plasma exchange. However, the response to the treatment was poor and both eyes eventually became blind. CONCLUSIONS: As best we know, this is the first case report of npAIR that developed in the fellow eye over 10 years after the development in the first eye. Long-term follow-up and a search for tumor lesions are necessary in cases of npAIR. Further understanding of the long-term course of AIR can contribute to an understanding of the pathology and treatment of npAIR.

Combination Treatment with Rituximab and Bortezomib in a Patient with Non-Paraneoplastic Autoimmune Retinopathy.

PURPOSE: To describe outcomes of combined rituximab and bortezomib treatment for non-paraneoplastic autoimmune retinopathy. CASE: A 37-year-old female developed photopsias and reduced vision. Electroretinography, optical coherence tomography, and positive serum anti-retinal antibodies were consistent with autoimmune retinopathy. A negative malignancy work-up specified her non-paraneoplastic presentation. Given absence of response to periocular steroids, azathioprine, and methotrexate, a combination of rituximab and bortezomib was initiated as fifth-line therapy. RESULTS: There was no significant improvement in the patient's symptoms or visual function following treatment. The full field electroretinogram amplitudes were reduced with progressive outer retinal degeneration evident on optical coherence tomography. Post-treatment anti-retinal antibody testing demonstrated the persistence of antibodies and revealed additional antibodies not previously detected. CONCLUSION: Combined rituximab and bortezomib treatment did not result in significant clinical improvement and there was evidence of disease progression. Further prospective studies are required to assess the efficacy of immunotherapy in patients with autoimmune retinopathy.

Autoimmune retinopathy with positive anti-recoverin antibodies not associated with neoplasms: Case report. / Retinopatía autoinmune con anticuerpos antirecoverina no asociado a neoplasia: a propósito de un caso.

The case is presented of a non-paraneoplastic autoimmune retinopathy (AIR) with positive anti-recoverin autoantibodies. A 28-year-old woman presented with a rapidly progressive bilateral visual loss of 8 months onset. Funduscopic examination revealed diffuse fine mottled atrophic changes in both eyes. Fluorescein angiographic studies showed a pattern of mottled areas of early hyperfluorescence without leakage of dye. In the ocular coherence tomography it was observed that was a loss of external layers. The electroretinogram showed absence of rod and cone responses in the right eye, and diminished cone response associated to absence of rod response in the left eye. AIR was suspected, and empirical corticosteroid treatment was started while waiting for Western-blot results, which was finally positive for recoverin, GAPDH, anti-alpha-enolase, and aldolase. The patient was able to be treated, and her visual acuity remained stable, but as soon as it was suspended, vision was completely lost in the right eye and reduced to hand movement in the left eye.

Longitudinal brain morphology in anti-NMDA receptor encephalitis: a case report with controls.

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a severe autoimmune condition, which typically affects young females. The long-term clinical consequences and brain morphology changes after anti-NMDAR encephalitis are not well known. CASE PRESENTATION: We present clinical and neuroimaging follow-up data on a 25-year female patient with typically presenting anti-NMDAR encephalitis. Longitudinal analyses of brain morphology were done using 3 T structural magnetic resonance imaging (sMRI) and Freesurfer analysis at the time of diagnosis and after symptomatic remission. The presented case attained good functional recovery after standard immunoglobulin-corticosteroid treatment but elevated serum NMDAR antibody levels persisted. The patient had no symptomatic relapses during a 3-year clinical follow-up. In the baseline brain sMRI scan there were no marked volume changes. However, a follow-up sMRI after 9 months indicated clear volume reductions in frontal cortical regions compared to matched controls with identical sMRI scans. CONCLUSIONS: This case report of anti-NMDAR encephalitis suggests that despite clinical recovery long-term brain morphological changes can develop in the frontal cortex. Longer clinical and imaging follow-up studies are needed to see whether these frontocortical alterations are fully reversible and if not, can they result in trait vulnerabilities for e.g. neuropsychiatric disorders.

Autonomic dysfunction is frequent and disabling in non-paraneoplastic sensory neuronopathies.

INTRODUCTION: Sensory neuronopathies (SN) are characterized by asymmetric non-length dependent sensory deficits and sensory ataxia. Autonomic dysfunction in SN was not yet evaluated regarding its frequency, characteristics and relationship to sensory deficits. To address these issues, we performed a comprehensive clinical and neurophysiological evaluation of a large cohort of patients with non-paraneoplastic SN (np-SN). METHODS: We enrolled 50 consecutive patients with npSN and 32 age/sex-matched healthy controls. They were clinically evaluated (SCOPA-Aut scale) and underwent neurophysiological autonomic assessment (quantitative sudomotor axon reflex test, heart rate variability and sympathetic skin response). RESULTS: Mean age of patients was 50.9 ±â€¯10.3 years and there were 18 men. npSN patients had higher SCOPA-Aut scores than controls (26.63 ±â€¯12.72 vs. 12.66 ±â€¯9.11, p < .001). QSART was abnormal in 92% of the patients - sweat volumes in all examined sites were smaller among patients (p < .001). Cardiovascular autonomic neuropathy was more frequent in these patients as well (p < .001). CONCLUSION: Altogether our results suggest that autonomic dysfunction in distinct domains is frequent in npSN patients. These findings suggest that the clinical picture of npSN is related to a double neuronopathy: sensory and autonomic.

Anterior cingulate cortex involvement in non-paraneoplastic limbic encephalitis.

BACKGROUND: Non-paraneoplastic limbic encephalitis is characterized by attention deficit, loss of emotion control, and impaired memory. Viral infection can cause acute encephalitis in children, occasionally exhibiting clinical features of limbic dysfunction. However, how viral infection affects the limbic system remains to be elucidated. CASE DESCRIPTION: A 5-year-old Japanese boy was admitted to our hospital because of high fever and status epilepticus. After seizures were controlled by diazepam, he exhibited attention deficit, loss of emotion control, and impaired memory, suggesting acute limbic encephalitis. Since titers of antibodies against Coxsackie virus A10 were significantly elevated in the serum, we diagnosed him with non-paraneoplastic limbic encephalitis associated with the viral infection. Brain magnetic resonance imaging demonstrated involvement of anterior cingulate cortex as well as white matter of the frontal lobe in the acute period. After steroid pulse therapy, these brain lesions subsequently disappeared in a time-dependent manner, beginning with the frontal lobe white matter and extending to the anterior cingulate cortex, and his psychological symptoms also disappeared. CONCLUSION: To the best of our knowledge, this is the first report to show the involvement of the region from the anterior cingulate cortex to the frontal lobe white matter. Clinical features such as seizures, attention deficit, loss of emotion control, and impaired memory suggest that this viral limbic encephalitis possibly extended from the frontal white matter to the anterior cingulate cortex via inter-neuronal connections in a time-dependent manner.

Non-paraneoplastic autoimmune retinopathy: multimodal testing characteristics of 13 cases.

BACKGROUND: Non-paraneoplastic autoimmune retinopathy (npAIR) is a rare autoimmune disease that primarily affects retinal photoreceptor function and results in profound and often times permanent vision loss. Delay in diagnosis and treatment initiation may contribute to the poor visual prognosis. METHODS: A retrospective chart review of all patients diagnosed with autoimmune retinopathy at the University of Wisconsin-Madison Eye Clinics between January 2012 and January 2017 was performed. Twenty eyes of 15 patients had evidence of any form of autoimmune retinopathy through a combination of symptoms, ocular findings, visual fields, optical coherence tomography, fundus autofluorescence, full-field and multifocal electroretinography, and serum anti-retinal antibodies. Clinical records were also analyzed for demographic data, systemic comorbidities, visual acuity, treatment employed, and disease progression. RESULTS: We identified 18 eyes from 13 patients who fit the criteria for non-paraneoplastic autoimmune retinopathy. Sixty-nine percent of patients were female with a mean age of symptom onset of 56.9 ± 20.3 years. Sixty-seven percent of eyes had an associated autoimmune condition, most commonly hypothyroidism. Serum testing revealed a preponderance of antibodies against carbonic anhydrase II, while imaging revealed characteristic changes. Fundus autofluorescence most commonly showed hyperautofluorescence around the macula. The delayed diagnosis led to a larger reduction in the horizontal extent of ellipsoid zone in 1-mm perifoveal area on optical coherence tomography with resulting visual decline. There was no difference in the change of visual acuity when stratifying for patients with autoimmune conditions (p = 0.52) or treatment status (p = 0.50). None of the patients who received treatment developed contralateral eye involvement or experienced disease progression based on visual acuity or symptoms. CONCLUSION: Non-paraneoplastic autoimmune retinopathy has a wide and often challenging to diagnose spectrum of clinical symptoms and imaging findings. Immunosuppressive therapy can be considered empiric in the face of a suggestive presentation and can be initiated after an evaluation of clinical findings and multimodal testing, though treatment does not appear to affect regeneration of the ellipsoid zone on OCT or impact visual acuity. Treatment should be primarily used to prevent disease progression and contralateral eye involvement. TRIAL REGISTRATION: N/A.

Cerebrospinal fluid markers of neuronal and glial cell damage in patients with autoimmune neurologic syndromes with and without underlying malignancies.

Autoimmune neurologic syndromes can be paraneoplastic (associated with malignancies and/or onconeural antibodies), or non-paraneoplastic. Their clinical presentation is often similar. As prognosis is related to malignancy treatment, better biomarkers are needed to identify patients with malignancy. We investigated cerebrospinal fluid (CSF) markers of neuronal (neurofilament light chain, NFL and total tau protein, T-tau) and glial (glial fibrillary acidic protein) damage. CSF-NFL and T-tau were increased in both paraneoplastic and non-paraneoplastic autoimmune syndromes. Patients with manifest malignancies were older, had less epilepsy, more focal central and peripheral neurological signs and symptoms, and worse long-term outcome, than those without malignancy. CSF-NFL-levels predicted long-term outcome but were not diagnostic for malignancy, after age adjustment.

Encefalitis Autoinmune Antirreceptor De NMDA: Reporte De Un Caso Y Revisión De La Literatura / Anti-NMDA Receptor Encephalitis: Case Report And Review Of Literature

Resumen La encefalitis por anticuerpos contra los receptores de N- Metil de aspartato (NMDA) está asociada con autoanticuerpos contra los heterómeros NR1/NR2 de los receptores de NMDA. Se presenta sobre todo en adultos jóvenes, con predominio en el sexo femenino, y buena respuesta al tratamiento. Su presentación clínica tiene manifestaciones neuropsiquiátricas, pasando por varias etapas hasta una recuperación gradual. Puede asociarse o no con la presencia de lesión tumoral Puede ser confundida fácilmente con encefalitis de tipo infecciosa por lo que es importante conocer su presentación clínica para un diagnóstico y tratamiento oportunos y así evitar mayor morbilidad y mortalidad. En este artículo se describe el caso de encefalitis autoinmune por anticuerpos contra los receptores NMDA en un hombre joven de 22 años de edad, ingresado en el Hospital Enrique Garcés de la ciudad de Quito- Ecuador y se hace una revisión de esta patología.

ABSTRACT Encephalitis caused by N-methyl-D-aspartate receptor antibodies is associated with auto antibodies against the heteromeric NR1/NR2 units of NMDA receptors. This type of encephalitis occurs more commonly in young adults, most of them women, and shows a good response to known treatments. Clinical features include neuropsychiatric manifestations, advancing through a series of stages up to a gradual recovery. This type of encephalitis can be associated with the presence, or lack thereof, lesions caused by tumors. It can easily be mistaken with infectious encephalitis, therefore is important to recognize its clinical features for an appropriate diagnosis and treatment in order to prevent higher morbidity and mortality. In this article, I describe a case study of autoimmune encephalitis caused by NMDA receptor antibodies in a twenty-two year old man, admitted to the Enrique Garcés Hospital in Quito-Ecuador, and I make a literature review on this pathology.

Acute psychosis due to non-paraneoplastic anti-NMDA-receptor encephalitis in a teenage girl: Case report.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is a disease occurring when antibodies produced by the body's own immune system attack NMDA-type glutamate receptors in the brain. Most anti-NMDAR encephalitis cases are associated with paraneoplastic syndrome. We analyze the case of a 15-year-old girl who was hospitalized in a child psychiatry clinic in Riga, Latvia, with de novo acute polymorphic psychotic disorder gradually progressing to a catatonic state. The patient received antipsychotic and electroconvulsive therapy with no beneficial effect. The council of doctors discussed differential diagnoses of schizophrenia-induced catatonia and the autoimmune limbic encephalitis-induced catatonic condition. When the diagnosis of anti-NMDAR autoimmune encephalitis was finally confirmed by repeated immunological assays (specific immunoglobulin [Ig] G and IgM in her blood serum and cerebrospinal fluid), and a paraneoplastic process was ruled out, she was started on immunomodulating therapy (methylprednisolone, Ig, plasmapheresis, rituximab), which changed the course of her disease. On immunomodulating treatment, her physical and mental health have gradually improved to almost complete reconvalescence. Psychiatrists should consider anti-NMDAR encephalitis as a differential diagnosis in first-episode psychosis patients presenting with disorientation, disturbed consciousness, pronounced cognitive deficits, movement disorder, dysautonomia, or rapid deterioration, and test for specific IgG NR1 autoantibodies, even if there are no specific findings on routine neuroimaging, electroencephalography (EEG), or cerebrospinal fluid tests.

A curious case of glaucoma?

An 84-year-old woman diagnosed with primary open-angle glaucoma was referred because her optic nerve appearance did not account for her visual field deficits. Further evaluation showed loss of color vision and rapid progression of visual field defects. Electroretinography revealed abnormal scotopic and photopic responses. Blood samples were positive for anti-retinal antibodies, but a malignancy work-up was negative, consistent with non-paraneoplastic autoimmune retinopathy.

Non-paraneoplastic Autoantibody-negative Limbic Encephalitis Characterized by Mild Memory Impairment: A Case Report

Encephalitis that primarily involves limbic system structures such as the hippocampus and parahippocampal gyrus has been described in early papers, most commonly characterized by a subacute progressive impairment of short-term memory, psychiatric features and seizures. While these findings might be caused by viral infections or systemic autoimmune disorders, many patients with limbic encephalitis have an immune-mediated etiology (paraneoplastic or not) characterized with serum or CSF antineuronal antibodies. This case reports about non-paraneoplastic autoantibody-negative limbic encephalitis in which there are no detection of antigens and no evidence of tumors.