Limbic Encephalitis Research Articles

Seizures in steroid-responsive encephalopathy.

Steroid-responsive encephalopathy is a general term for diseases that are characterized by diffuse brain injury and respond well to corticosteroids or immunosuppressive agents, including Hashimoto's encephalopathy (HE), limbic encephalitis (LE), systemic lupus erythematosus encephalopathy (SLEE), antineutrophil cytoplasmic antibodies (ANCA)-associated systemic vasculitis encephalopathy (AASV), viral encephalitis (VE), and primary central nervous system lymphoma (PCNSL). Epilepsy and status epilepticus are the main manifestations of steroid-responsive encephalopathy. The spectrum of "autoimmune epilepsy" diseases, which has been approved by the epilepsy diagnostic recommendations of the International Antiepileptic League, is characterized by a high prevalence of epilepsy in central nervous system (CNS) autoimmune diseases and a variety of neuron-specific autoantibodies. Steroid-responsive encephalopathy with different causes may have different pathogeneses and has been suggested to be associated with some internal commonality producing seizure as the main symptom. Determining the regularity of seizures caused by steroid-responsive encephalopathy and implementing appropriate measures will help us improve the prognosis of patients. This paper summarizes the epidemiology, seizure onset, seizure type, and other characteristics of seizures in steroid-responsive encephalopathy (including HE, LE, SLEE, ANCA-associated systemic vasculitis encephalopathy, VE, and PCNSL) and then discusses the use of antiepileptic drugs to treat steroid-responsive encephalopathy.

Expanding the Catatonia Tent: Recognizing Electroconvulsive Therapy Responsive Syndromes.

Catatonia is a motor and mood disorder of behavior increasingly recognized in systemic medically ill. Neuroleptic malignant syndrome, delirious mania, self injurious behaviors in autism, and limbic encephalitis are conditions in which ECT-responsive catatonia is increasingly recognized and effectively treated.

An uncommon presentation of paraneoplastic limbic encephalitis

Paraneoplastic limbic encephalitis (PLE) is a rare disease with established diagnostic criteria.We describe a case of an uncommon presentation of PLE in a female who presented with a one- year duration of short-term memory loss and mild behavioral changes who was eventually diagnosed with PLE associated with breast cancer.Our case demonstrates atypical presentation of PLE, with chronic presentation and an uncharacteristic mild neurological symptoms.This case aims to highlight the importance of a diagnostic work up of autoimmune encephalitis in selected cases that does not present with common diagnostic criteria.

Anti-LGI1 Antibody Limbic Encephalitis Associated with Hepatocellular Carcinoma

Anti-leucine-rich glioma inactivated-1 (LGI1) antibody has been known as the most common antibody in autoimmune limbic encephalitis. We report a case of a 63-year-old woman who presented with repetitive memory impairment. She was diagnosed with anti-LGI1 limbic encephalitis by clinical symptoms, magnetic resonance imaging, electroencephalography, and antibody test. Hepatocellular carcinoma (HCC) was discovered incidentally. Clinical seizures were completely controlled after hepatic segmentectomy without immunotherapy. This is the first case report showing the relationship between HCC and anti-LGI1 limbic encephalitis.

A scoping review on paraneoplastic autoimmune limbic encephalitis (PALE) psychiatric manifestations.

The term limbic encephalitis has been used with an oncological precedent for over 50years and, since then, has been applied in relation to multiple antibodies found in its etiological process. Over the last decade, the psychiatric community has brought paraneoplastic autoimmune limbic encephalitis (PALE) to a new light, scattering the once known relationships between said screened antibodies responsible for causing limbic encephalitis. Due to the fact that some individuals with this condition have a psychiatric syndrome as an initial manifestation, the aim of this updated scoping review is to reestablish a causal relationship between the onconeuronal autoantibodies, both intracellular and extracellular, possible underlying malignancies and subsequent neuropsychiatric syndrome. In pair with it, there is the idea of sketching a cleaner thorough picture of what poses as psychiatric symptoms as well as possible therapeutics. Even though the always evolving epistemology of the neurosciences achieved a significant unveiling of what includes PALE in its relevant pathological subgroups, the amount of gray literature still is much superior, appealing to a further research with more randomized controlled trials, with larger populations, so that the results corroborate the small amount of data that already exist and posteriorly be applied in the general population.

Paraneoplastic Limbic Encephalitis Secondary To Mixed Non-Seminomatous Germ Cell Tumours

Abstract Casestudy: Testicular tumors account for 1–2% of all tumors in men, with 95% of these being germ cell tumors. The main risk factor for the development of testicular cancer is cryptorchidism. Paraneoplastic limbic encephalitis is a rare sequela of testicular tumor associated with anti-Ma2 and KLH11 antibodies. The most effective treatment for paraneoplastic limbic encephalitis is treatment of the primary malignancy. We present a 41-year-old male that presented to the emergency department with two weeks of episodic alteration of consciousness and memory disturbances. Negative neurologic evaluation and imaging led to concern for a paraneoplastic process from a distant malignancy. CT imaging revealed an enlarged, necrotic para-aortic lymph node and subsequent ultrasound demonstrated a right sided testicular mass. Right radical orchiectomy was performed. Microscopically, the mass consisted of mixed respiratory epithelium, gastrointestinal glands and squamous epithelium with keratinization consistent with a post-pubertal testicular teratoma with associated in-situ germ cell neoplasia. Resection of the para-aortic mass revealed large anaplastic cells with epithelioid features, nuclear pleomorphism and frequent mitoses. Immunostaining was positive for Pan-Keratin and OCT4, consistent with poorly differentiated embryonal carcinoma. Resection of the primary and metastatic disease, as well as treatment with corticosteroids resulted in resolution of the encephalitis. This presentation of severe neurological disturbances in the setting of a metastatic mixed nonseminomatous germ cell tumor represents a rare presentation of paraneoplastic limbic encephalitis.

LGI1 downregulation increases neuronal circuit excitability.

Leucine-rich glioma-inactivated 1 (LGI1) is a secreted transsynaptic protein that interacts presynaptically with Kv1.1 potassium channels and a disintegrin and metalloprotease (ADAM) protein 23, and postsynaptically influences α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors through a direct link with the ADAM22 cell adhesion protein. Haploinsufficiency of LGI1 or autoantibodies directed against LGI1 are associated with human epilepsy, generating the hypothesis that a subacute reduction of LGI1 is sufficient to increase network excitability. We tested this hypothesis in ex vivo hippocampal slices and in neuronal cultures, by subacutely reducing LGI1 expression with shRNA. Injection of shRNA-LGI1 in the hippocampus increased dentate granule cell excitability and low-frequency facilitation of mossy fibers to CA3 pyramidal cell neurotransmission. Application of the Kv1 family blocker, α-dendrotoxin, occluded this effect, implicating the involvement of Kv1.1. This subacute reduction of LGI1 was also sufficient to increase neuronal network activity in neuronal primary culture. These results indicate that a subacute reduction in LGI1 potentiates neuronal excitability and short-term synaptic plasticity, and increases neuronal network excitability, opening new avenues for the treatment of limbic encephalitis and temporal lobe epilepsies.

Imaging Review of Paraneoplastic Neurologic Syndromes.

Paraneoplastic syndromes are systemic reactions to neoplasms mediated by immunologic or hormonal mechanisms. The most well-recognized paraneoplastic neurologic syndrome, both clinically and on imaging, is limbic encephalitis. However, numerous additional clinically described syndromes affect the brain, spinal cord, and peripheral nerves. Many of these syndromes can have imaging findings that, though less well described, are important in making the correct diagnosis. Moreover, imaging in these syndromes frequently mimics more common pathology, which can be a diagnostic challenge for radiologists. Our goal is to review the imaging findings of paraneoplastic neurologic syndromes, including less well-known entities and atypical presentations of common entities. Specifically, we discuss limbic encephalitis, paraneoplastic cerebellar degeneration, paraneoplastic brain stem encephalitis, cranial neuropathy, myelitis, and polyneuropathy. We also demonstrate common diagnostic pitfalls that can be encountered when imaging these patients.

Association between Parkinsonian subtype Multiple System Atrophy and Anti-Glutamic Acid Decarboxylase antibodies in Stiff Person Spectrum Disorder (SPSD). Case Report

Objectives: Patients with Anti-Glutamic Acid Decarboxylase antibodies (Anti-GAD) have low levels of GABA synthesis which can manifest as motor and cognitive dysfunction such as Stiff-Person Syndrome and variants, stiff-leg syndrome, insulin-dependent diabetes mellitus, cerebellar ataxia, limbic and extra-limbic encephalitis, progressive encephalopathy with limb rigidity (PERM), oculomotor dysfunction and drug-resistant epilepsy.

Clinical Presentation and Outcomes of Severe Acute Respiratory Syndrome Coronavirus 2-Related Encephalitis: The ENCOVID Multicenter Study.

BackgroundSeveral preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes.MethodsThe ENCOVID multicentre study included patients with encephalitis with full infectious screening, CSF, EEG, MRI data and confirmed SARS-CoV-2 infection recruited from 13 centres in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded.Resultstwenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by RT-PCR resulted negative. Based on MRI, cases were classified as ADEM (n=3), limbic encephalitis (LE, n=2), encephalitis with normal imaging (n=13) and encephalitis with MRI alterations (n=7). ADEM and LE cases showed a delayed onset compared to the other encephalitis (p=0.001) and were associated with previous more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to other encephalitis.ConclusionsSARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment and outcomes.

Mixed Brain Pathology Is the Most Common Cause of Cognitive Impairment in the Elderly.

Systemic diseases, diabetes mellitus (DM), and cardiovascular disease (CaVD) have been suggested being risk factors for cognitive impairment (CI) and/or influence Alzheimer's disease neuropathologic change (ADNC). The purpose was to assess the type and the extent of neuropathological alterations in the brain and to assess whether brain pathology was associated with CaVD or DM related alterations in peripheral organs, i.e., vessels, heart, and kidney. 119 subjects, 15% with DM and 24% with CI, age range 80 to 89 years, were chosen and neuropathological alterations were assessed applying immunohistochemistry. Hyperphosphorylated τ (HPτ) was seen in 99%, amyloid-β (Aβ) in 71%, transactive DNA binding protein 43 (TDP43) in 62%, and α-synuclein (αS) in 21% of the subjects. Primary age related tauopathy was diagnosed in 29% (more common in females), limbic predominant age-related TDP encephalopathy in 4% (14% of subjects with CI), and dementia with Lewy bodies in 3% (14% of subjects with CI) of the subjects. High/intermediate level of ADNC was seen in 47% and the extent of HPτ increased with age. The extent of ADNC was not associated with the extent of pathology observed in peripheral organs, i.e., DM or CaVD. Contrary, brain alterations such as pTDP43 and cerebrovascular lesions (CeVL) were influenced by DM, and CeVL correlated significantly with the extent of vessel pathology. In most (66%) subjects with CI, the cause of impairment was "mixed pathology", i.e., ADNC combined with TDP43, αS, or vascular brain lesions. Furthermore, our results suggest that systemic diseases, DM and CaVD, are risk factors for CI but not related to ADNC.

Anti-N-methyl-d-aspartate Receptor Encephalitis Related Sinus Node Dysfunction and the Lock-Step Phenomenon.

Described in 2007, anti-N-methyl-d-aspartate receptor encephalitis (ANMDARE) is a rare autoimmune limbic encephalitis affecting young adults (predominantly women of reproductive age) and is a paraneoplastic manifestation of ovarian teratoma in about half of the cases. ANMDARE is characterized by psychiatric changes, neurological changes, autonomic instability and cardiac dysrhythmias. In this report, we present a 36-year-old woman who was 16 weeks pregnant and brought to the hospital with confusion and subsequently had a seizure with Electroencephalography (EEG) demonstrated an extreme delta brush pattern consistent with ANMDARE. Patient developed sinus nodal dysfunction and was also found to have ovarian teratoma, a rather typical presentation for ANMDARE, that is considered a paraneoplastic syndrome for ovarian teratoma. In this report, we highlight the cardiac manifestation of ANMDARE, the pathophysiology associated with autonomic instability, and management strategies of this rare, and largely devastating illness.

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.

Blood and cerebrospinal fluid immune cell profiles in patients with temporal lobe epilepsy of different etiologies

Inflammation plays a role in the pathogenesis of immune-mediated epilepsy, but also in epilepsy of other etiology such as hippocampal sclerosis. This study aimed to characterize immune cell signatures in the peripheral blood (PB) and cerebrospinal fluid (CSF) in temporal lobe epilepsy (TLE) of different etiologies. We retrospectively evaluated CSF routine parameters and immune cell profiles using flow cytometry in a cohort of 51 patients and 45 age-matched controls with functional disorders. Groups were comprised of patients with nonlesional TLE (n=26), TLE due to hippocampal sclerosis (n=14), or limbic encephalitis with antibodies against the 65-kDa isoform of glutamic acid decarboxylase (GAD65-LE; n=11). TLE patients showed increased proportions of human leukocyte antigen-DR isotype (HLA-DR)-expressing CD4+ T lymphocytes in the CSF. Furthermore, they were characterized by a shift in monocyte subsets toward immature CD14low CD16+ cells in the PB and blood/CSF-barrier dysfunction. Whereas TLE patients in general showed similar immune cell profiles, patients with GAD65-LE differed from other TLE patients by increased proportions of HLA-DR-expressing CD8+ T lymphocytes and type 2/3 oligoclonal bands. These findings point to a role of innate and adaptive immunity in TLE. CSF parameters may help to discriminate epilepsy patients from controls and different forms of TLE from each other.

A rare case of anti-LGI1 limbic encephalitis with concomitant positive NMDAR antibodies

BackgroundN-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated 1 (LGI1) antibodies define the most prevalently recognized autoimmune encephalitis syndromes, while the simultaneous occurrence of both conditions has hardly been published before.Case presentationWe report the case of a 67-year-old patient who presented with generalized tonic–clonic seizures (GTCS) followed by behavioral changes, psychosis, sleep disorders, decreased consciousness, and faciobrachial dystonic seizures. Ancillary findings included serum hyponatremia and imaging evidence of high-intensity lesions within bilateral medial temporal lobes on T2-weighted fluid attenuation inversion recovery. Both LGI1 and NMDAR antibodies were positive in serum and cerebral spinal fluid using transfected cell based assays. Despite prominent clinical features of anti-LGI1 limbic encephalitis (LGI1-LE), the patient also exhibited overlapping symptoms of anti-NMDAR encephalitis, like early-onset GTCS, which might be related to the concomitant positive NMDAR antibodies.ConclusionsWe report a rare case of LGI1-LE with overlapping symptoms and simultaneous positive NMDAR antibodies. It is necessary to evaluate the presence of NMDAR antibodies in certain LGI1-LE patients with unusual symptoms. However, caution should be exercised in interpreting the observation, given the fact of a single-case study.

Clinical characteristics of patients double positive for CASPR2 and LGI1-antibodies

ObjectivesThis study described the clinical characteristics of autoimmune neurological diseases with dual seropositive antibodies of CASPR2 and LGI1. Patients and MethodsThree patients, with antibodies targeting both CASPR2 and LGI1 (EUROIMMUN, FA 112d-1, Germany), hospitalized in Department of Neurology, Xuanwu Hospital, Capital Medical University from June 2016 to June 2019 were collected in this study. We summarized the clinical characteristics of patients with CASPR2 and LGI1 antibodies from a targeted literature review. ResultsThree patients reported were all middle-aged and elderly male with diverse neurological symptoms, including seizures, psychological abnormalities, limb weakness and hyperhidrosis. Interestingly, three patients displayed three different clinical syndromes (isolated epilepsy, Morvan syndrome and limbic encephalitis, respectively). White blood cell and glucose in Cerebrospinal fluid (CSF) were normal and CSF for protein was slightly elevated. Electromyography (EMG) showed abnormal spontaneous firing in case 2. Brain magnetic resonance imaging (MRI) revealed bilateral hyper-intensity of the temporal lobe on T2 and FLAIR sequence in case 3. Cancer screening program of patient 2 showed thymoma. Cell based assay was positive in serum for both LGI1 and CASPR2 antibodies, while these antibodies were negative in CSF. They were treated with glucocorticoid or intravenous immunoglobulin (IVIG). Followed up for 6 months to 1 year, all patients got remission to different extent. ConclusionThrough the detailed analysis of three patients, the combination of both antibodies contributes to a broad spectrum of neurological symptoms in the central, peripheral, and autonomic nervous systems. The patients with same antibodies can have different clinical syndromes. Early tumor screening and immunotherapy will improve the prognosis of the disease.

Specific B- and T-cell populations are associated with cognition in patients with epilepsy and antibody positive and negative suspected limbic encephalitis

ObjectiveNeuropsychological impairments are major symptoms of autoimmune limbic encephalitis (LE) epilepsy patients. In LE epilepsy patients with an autoimmune response against intracellular antigens as well as in antibody-negative patients, the antibody findings and magnetic resonance imaging pathology correspond poorly to the clinical features. Here, we evaluated whether T- and B-cells are linked to cognitive impairment in these groups.MethodsIn this cross-sectional, observational, case–controlled study, we evaluated 106 patients with adult-onset epilepsies with a suspected autoimmune etiology. We assessed verbal and visual memory, executive function, and mood in relation to the presence or absence of known auto-antibodies, and regarding T- and B-cell activity as indicated by flow cytometry (fluorescence-activated cell sorting = FACS, peripheral blood = PB and cerebrospinal fluid = CSF).Results56% of the patients were antibody-negative. In the other patients, auto-antibodies were directed against intracellular antigens (GAD65, paraneoplastic: 38%), or cellular surface antigens (LGI1/CASPR2/NMDA-R: 6%). Excluding LGI1/CASPR2/NMDA-R, the groups with and without antibodies did not differ in disease features, cognition, or mood. CD4+ T-cells and CD8+ T-cells in blood and CD4+ T-cells in CSF were prominent in the auto-antibody positive group. Regression analyses indicated the role education, drug load, amygdala and/or hippocampal pathology, and CD4+ T-cells play in verbal memory and executive function. Depressed mood revealed no relation to flow cytometry results.ConclusionOur results indicate a link between T- and B-cell activity and cognition in epilepsy patients with suspected limbic encephalitis, thus suggesting that flow cytometry results can provide an understanding of cognitive impairment in LE patients with autoantibodies against intracellular antigens.

Update on the Biology, Management, and Treatment of Small Cell Lung Cancer (SCLC).

Small-cell lung cancer (SCLC) accounts for 13–15% of all new lung cancer cases in the US. The tumor has a tendency to disseminate early resulting in 80–85% of patients being diagnosed with extensive disease (ES-SCLC). Chemotherapy has provided SCLC patients considerable survival benefits over the past three decades. Nonetheless, most patients relapse and rarely survive beyond 2 years. Despite consistent overall response rates of ≥50%, until recently, median survival times and 2-year survivals only ranged between 7–10 months and 10–20%, respectively. Several chemotherapy agents possess activity against SCLC, both, as single agents and in combinations but etoposide-platinum emerged as the preferred first line regimen. Upon relapse, many patients remain candidates for additional therapy. However, the sensitivity of relapsed SCLC to further therapies is markedly reduced and dependent upon the level and duration of response to the initial treatment (platinum-sensitive vs. resistant relapse). Multiple factors suggest a therapeutic role for immunotherapy in SCLC: SCLC has been associated with immune-mediated paraneoplastic processes (cerebellar degeneration, limbic encephalitis, and Lambert–Eaton syndrome) and patients presenting with these paraneoplastic syndromes have shown more favorable outcomes, suggesting an underlying immune response mechanism.Comprehensive genomic profiling of SCLC indicates that the majority lack functional p53 (90%) and Rb1 (65%). These universal genetic aberrations facilitate poor genomic stability, thus perpetuating the generation of tumor associated antigens, amenable to targeting with immunotherapy.SCLC has one of the highest mutational loads, likely a reflection of the myriad of insults inflicted by smoking-related carcinogens. The relationship between tumor mutational load and response to immune checkpoint inhibitors has been established in multiple solid tumors, including preliminary results in relapsed SCLC.In this manuscript, we review the early (some failed and discontinued, some partly successful, and still ongoing) attempts to incorporate immunotherapy (particularly vaccine based approaches) to the treatment of SCLC, and the latest attempts (mostly incorporating the use of checkpoint inhibitors), including those with favorable but preliminary results (CheckMate 032, Keynote 028 and 158), and those with more definitive positive (iMpower 133 and CASPIAN) and negative (CheckMate 331 and 451) results.

Fundamental Mechanisms of Autoantibody-Induced Impairments on Ion Channels and Synapses in Immune-Mediated Cerebellar Ataxias.

In the last years, different kinds of limbic encephalitis associated with autoantibodies against ion channels and synaptic receptors have been described. Many studies have demonstrated that such autoantibodies induce channel or receptor dysfunction. The same mechanism is discussed in immune-mediated cerebellar ataxias (IMCAs), but the pathogenesis has been less investigated. The aim of the present review is to evaluate what kind of cerebellar ion channels, their related proteins, and the synaptic machinery proteins that are preferably impaired by autoantibodies so as to develop cerebellar ataxias (CAs). The cerebellum predictively coordinates motor and cognitive functions through a continuous update of an internal model. These controls are relayed by cerebellum-specific functions such as precise neuronal discharges with potassium channels, synaptic plasticity through calcium signaling pathways coupled with voltage-gated calcium channels (VGCC) and metabotropic glutamate receptors 1 (mGluR1), a synaptic organization with glutamate receptor delta (GluRδ), and output signal formation through chained GABAergic neurons. Consistently, the association of CAs with anti-potassium channel-related proteins, anti-VGCC, anti-mGluR1, and GluRδ, and anti-glutamate decarboxylase 65 antibodies is observed in IMCAs. Despite ample distributions of AMPA and GABA receptors, however, CAs are rare in conditions with autoantibodies against these receptors. Notably, when the autoantibodies impair synaptic transmission, the autoimmune targets are commonly classified into three categories: release machinery proteins, synaptic adhesion molecules, and receptors. This physiopathological categorization impacts on both our understanding of the pathophysiology and clinical prognosis.

Fatal familial insomnia: A new case description with early response to immunotherapy

Fatal Familial Insomnia (FFI) is a rare prionopathy with autosomal dominant inheritance. Although it owes its name because insomnia is one of the most frequent and core symptoms, its clinical phenotype can be wide and heterogeneous. This usually makes it necessary to rule out other clinical processes, such as limbic encephalitis or Creutzfeldt Jakob disease, whose symptoms can sometimes overlap.We present the case of a 46-year-old male with a rapidly progressive multidomain cognitive impairment, associated with instability in gait, myoclonus and persistent and progressive insomnia. His mother had died from a genetically determined FFI (D178N mutation). Due to clinical course, an immunomediated encephalopathy was suspected, and immunosuppressive treatment with steroids and immunoglobulins was initiated. The patient showed initial improvement, but later rapidly progressive deterioration until his death 7 months after clinical onset.Cranial magnetic resonance, electroencephalogram and cerebrospinal fluid (CSF) did not show any findings. The antiTPO and antineuronal antibodies were negative. The genetiic study demonstrated the missense mutation c.532G > A (p.Asp178Asn) compatible with FFI. Postmortem study showed synaptic deposits of PrPsc in the entorhinal cortex and in thalamus, which confirmed FFI diagnosis.