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Hodgkin lymphoma is a malignant disease with clonal proliferation of B-cells and high-level reactive inflammatory microenvironment. The main clinical sings are lymphadenopathy and toxic symptoms. Neurological symptoms as usual can be a result of compression or tumor infiltration of nervous structures. The primary damage of CNS occurs from 0,2% to 0,5% of all cases HL. Paraneoplastic neurological syndrome is a group of rare (an average 1 case on 10000 patients) neurological disorders against the background of oncological process. The pathophysiologic mechanism is due to production of antibody which is both to tumor cells and nerve cells. These antibodies are called onconeural autoantibodies. The hallmark which make diagnostics harder is the fact that onconeural autoantibodies rare take place in patients with lymphomas unless anti-Tr and anti-mGluR1 in patients with limbic encephalitis or paraneoplastic cerebellar degeneration. There are two case reports about patients with PNS in onset of Hodgkin lymphoma in article.

Case series summary Seven cases of feline hippocampal and piriform lobe necrosis (FHN) are described, with particular emphasis on clinical, radiographic and histopathological correlations. FHN is an uncommon acute epileptic condition resembling human autoimmune limbic encephalitis and temporal lobe epilepsy. Seizures are typically focal and feature uni- or bilateral orofacial or head twitching, hypersalivation, lip smacking, mydriasis, vocalisation and motionless staring, with inter-ictal behavioural changes such as unprovoked aggression and rapid running. Emerging evidence supports an autoimmune aetiology, although disruption of hippocampal architecture secondary to brain neoplasia has also been recognised. Most commonly, however, the underlying cause remains unknown. Diagnosis is achieved clinically and with brain MRI; electroencephalography and voltage-gated potassium channel-complex autoantibodies are currently the subject of research. Affected cats are frequently refractory to conventional antiepileptic treatment. Relevance and novel information Following a review of the literature, including potential complicating factors and comparisons with human medicine, the hippocampus and piriform lobe are proposed as the neuroanatomical localisation for focal seizures with orofacial involvement in cats, regardless of aetiology.

Paraneoplastic limbic encephalitis (PLE) is an immunopathologic syndrome associated with malignancy and represents a rare remote outcome of tumor on the nervous system. We report a case of PLE caused by a regressed testicular germ cell tumor in an otherwise healthy young man, who presented with acute-onset confusion, memory impairment and anterograde amnesia. Prompt recognition of PLE is critical as it allows early treatment of both the primary tumor and PLE-related neurologic impairments, which can be severe and irreversible if treatment is delayed. Complete tumor treatment response offers the best chance for neurologic recovery in patients with PLE. To our knowledge, this is the second reported case of PLE with radiologic-pathologic correlation in the setting of a regressed testicular germ cell tumor.

Paraneoplastic neurological syndromes (PNS) are rare immune-mediated disorders, and the detection of onconeural antibodies is helpful for PNS diagnosis. The aim of this study was to investigate the clinical characteristics of patients with PNS with positive onconeural antibodies in a single center in Hubei, China. We retrospectively analyzed the clinical characteristics of 54 patients with positive onconeural antibodies from January 2016 to September 2020. Among 780 patients with suspected PNS, 54 (6.9%) had positive onconeural antibodies. Of those 54 patients, 28 (51.8%) were diagnosed with definite PNS and 13 (24.1%) with possible PNS. Eighteen (33.3%) patients were confirmed with cancer. Ten PNS syndromes were detected among the 28 patients with definite PNS, and they had either classical (12/28, 42.8%) or non-classical syndromes (17/28, 60.7%). Peripheral neuropathy (9/28, 32.1%), subacute cerebellar degeneration (4/28, 14.3%), and limbic encephalitis (4/28, 14.3%) were the most common PNS syndromes. The anti-CV2/CRMP5-antibody was observed most frequently. Lung cancer was the most common tumor type. For patients with possible PNS, peripheral neuropathy was the most common PNS syndrome, and the anti-Tr-antibody was the most frequent onconeural antibody. Immunotherapy was effective in treating PNS. The anti-CV2/CRMP5-antibody was the most subsequently observed antibody. The manifestations of PNS are diverse and include peripheral neuropathy, subacute cerebellar degeneration, and limbic encephalitis. In patients with PNS, lung cancer was the most common tumor.

Neoplastic meningitis (NM) and paraneoplastic syndromes (PNSs) are a rare group of disorders present in patients with cancer. Clinical diagnosis of these conditions is challenging, and imaging and laboratory analysis play a significant role in diagnosing. Diagnosis of NM largely depends on documenting circulating tumor cells in the cerebrospinal fluid (CSF) and/or leptomeningeal and nodular enhancement on contrast-enhanced MR imaging of the brain or axial spine. PNSs encompass a variety of symptoms or syndromes. Paraneoplastic neuronal disorder diagnosis requires a multidimensional approach, high clinical suspicion, CSF and serum examination, and imaging. Neuroimaging is an integral part in the evaluation.

OBJECTIVE Limbic encephalitis (LE) comprises a spectrum of inflammatory changes in affected brain structures including the presence of autoantibodies and lymphoid cells. However, the potential of distinct lymphocyte subsets alone to elicit key clinicopathological sequelae of LE potentially inducing temporal lobe epilepsy (TLE) with chronic spontaneous seizures and hippocampal sclerosis (HS) is unresolved. METHODS Here, we scrutinized pathogenic consequences emerging from CD8+ T cells targeting hippocampal neurons by recombinant adeno-associated virus-mediated expression of the model-autoantigen ovalbumin (OVA) in CA1 neurons of OT-I/RAG1-/- mice (termed "OVA-CD8+ LE model"). RESULTS Viral-mediated antigen transfer caused dense CD8+ T cell infiltrates confined to the hippocampal formation starting on day 5 after virus transduction. Flow cytometry indicated priming of CD8+ T cells in brain-draining lymph nodes preceding hippocampal invasion. At the acute model stage, the inflammatory process was accompanied by frequent seizure activity and impairment of hippocampal memory skills. Magnetic resonance imaging scans at day 7 of the OVA-CD8+ LE model revealed hippocampal edema and blood-brain barrier disruption that converted into atrophy until day 40. CD8+ T cells specifically targeted OVA-expressing, SIINFEKL-H-2Kb -positive CA1 neurons and caused segmental apoptotic neurodegeneration, astrogliosis, and microglial activation. At the chronic model stage, mice exhibited spontaneous recurrent seizures and persisting memory deficits, and the sclerotic hippocampus was populated with CD8+ T cells escorted by NK cells. INTERPRETATION These data indicate that a CD8+ T-cell-initiated attack of distinct hippocampal neurons is sufficient to induce LE converting into TLE-HS. Intriguingly, the role of CD8+ T cells exceeds neurotoxic effects and points to their major pathogenic role in TLE following LE. ANN NEUROL 2021;89:666-685.

This case was a 50-year-old healthy woman. After repeated transient amnesia, she developed tonic-clonic seizures and was admitted to our hospital. The brain MRI showed FLAIR hyperintensities in the left temporal lobe and EEG showed an epileptic discharge starting from the left temporal region. Based on these findings, we diagnosed temporal lobe epilepsy associated with acute limbic encephalitis. While she experienced recurrent transient amnesia, her cognitive functions were preserved except for her memory. These symptoms and EEG findings were consistent with transient epileptic amnesia (TEA). Acute limbic encephalitis that occurred in a healthy middle-aged woman may be antibody-mediated encephalitis, requiring immediate immunotherapies. In this case, GABAB receptor antibodies in cerebrospinal fluid were found positive. This is the first report showing that TEA was caused by GABAB receptor autoimmune encephalitis.

Introduction: Antibodies to Voltage Gated Potassium Channels (VGKC) are directed against Leucine-rich Glioma- Inactivated1 (LGI1) and Contactin Associated Protein like 2 (Caspr2). Common presentations of Caspr2 antibody associated diseases include limbic encephalitis, Morvan’s syndrome and acquired neuromyotonia. New clinical phenotypes are being considered to the spectrum of Caspr2 antibody associated disease. Here we report a case of Caspr2 antibody associated disease with an unusual clinical presentation. Case Report: 40 year old male presented with distal symmetrical sensorimotor neuropathy of 4 months duration. Subsequently he had developed neurobehavioral symptoms in the form of irritability, episodic memory impairment and seizures. After medical evaluation he was diagnosed to have anti Caspr2 antibody associated disease. Patient showed improvement with an immunosuppressive therapy, but had recurrence of autoimmune encephalitis 1 month later. Along with that, he had also developed right vocal cord palsy, for which no other cause was identified. Patient improved with second line immunosuppressive therapy. He had no further recurrence and is under follow up. Keywords: Voltage gated potassium channels, Leucine-rich Glioma-inactivated 1, Contactin associated protein, Limbic encephalitis, Neuromyotonia.

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.

We herein report a 50-year-old man with alcoholic cirrhosis who developed loss of consciousness and tremor of the upper limbs. Magnetic resonance imaging findings were suggestive of limbic encephalitis with bilateral hippocampal damage, and a cerebrospinal fluid (CSF) examination confirmed anti-N-methyl-D-aspartate (NMDA) and anti-glutamate receptor antibodies. Despite initial corticosteroid therapy, meningeal irritation symptoms appeared, owing to the development of cryptococcal meningitis (CM), diagnosed by the detection of cryptococcal capsular polysaccharide antigen in the follow-up CSF analysis. Cerebral infarction with reversible stenosis of major cerebral arteries during the clinical course was also observed. Following administration of antifungals and corticosteroids, the number of cells in the CSF gradually declined, and NMDA receptor antibodies disappeared. Our study demonstrates the unique coexistence of CM with anti-NMDA receptor encephalitis in adults.

Paraneoplastic neurological syndromes (PNS) associated with anti-CV2/CRMP5 antibodies are rare in the literature. Various clinical manifestations can occur including paraneoplastic limbic encephalitis (PLE). Thymoma is one of the rare causes that can be associated with this syndrome. It has not been reported in the literature in children or adolescents to the best of our knowledge. We report a case of PLE in a 19-year-old male patient secondary to thymoma that was diagnosed after 5 years of onset. Anti-CV2/CRMP5 antibodies were positive in the serum and became negative after thymectomy. Diagnosis of PNS should be evoked in cases with atypical neurological manifestation and can be confirmed by the presence of onconeuronal antibodies. We report the first pediatric PLE secondary to thymoma associated with anti-CV2/CRMP5 antibodies.

Background We describe the clinical and neuropathological features of a patient with T-cell-mediated paraneoplastic limbic encephalitis, parkinsonism, hypothermia, and narcolepsy-like presentation associated with endometrial carcinoma. Objectives This patient with prominent parkinsonism and narcolepsy broadens the phenotype of known paraneoplastic syndromes and demonstrates the importance of investigation for occult malignancy even in the absence of paraneoplastic antibodies. Methods This is a case report with diagnosis confirmed at postmortem. Results Paraneoplastic antibodies were not detected. The initial improvement with immunosuppression was short lived, and postmortem neuropathological examination demonstrated encephalitis with predominant T-cell infiltration affecting the hypothalamus and extending to the brainstem, suggestive of a paraneoplastic syndrome. Conclusions Although the possibility of a novel antibody cannot be ruled out, consideration must also be given to recent demonstration of purely T-cell-mediated neuronal destruction in the context of paraneoplastic syndromes.

An 84-year-old man was admitted to our hospital with new-onset refractory status epilepticus of unclear etiology. On the third day, diffusion-weighted brain MRI demonstrated lesions in the right medial temporal and parietal lobes. As a CSF sample showed pleocytosis, paraneoplastic limbic encephalitis (PLE) associated with small cell lung cancer (SCLC) was suspected. The patient was also positive for anti-gamma aminobutyric acid (GABA)B receptor antibody in the CSF, which has recently been reported in elderly patients with SCLC-related PLE. Methylprednisolone pulse therapy ameliorated the symptoms. It is noteworthy that immune therapy often improves the symptoms of PLE with anti-GABAB receptor antibody, even though radical therapy for the lung cancer may be difficult.

Various neuropathologies produce hyperintense signals on T2-weighted or fluid-attenuated inversion recovery sequences of the temporal lobes. Recognition of the distribution pattern and associated findings may narrow the spectrum of differential diagnoses or suggest a specific disease. This pictorial essay aims to illustrate the relatively common diseases that affect the temporal lobe, such as herpes simplex encephalitis, neurosyphilis, limbic encephalitis, postictal edema, neoplasia, and multiple sclerosis, as well as those that are less common, such as myotonic dystrophy type 1, CADASIL, and CARASIL, together with the particularities of each entity.Diversas neuropatologias apresentam hipersinal em T2 ou FLAIR nos lobos temporais, porém, o reconhecimento do padrão de distribuição e achados associados podem estreitar o espectro de diagnósticos diferenciais ou sugerir uma doença específica. Este ensaio iconográfico visa demonstrar doenças que acometem o lobo temporal e que são relativamente comuns no dia-a-dia dos radiologistas, como encefalite herpética, neurossífilis, encefalite límbica, edema pós-crise convulsiva, glioma e esclerose múltipla, e outras nem tão comuns como distrofia miotônica tipo I, CADASIL e CARASIL, atentando para as particularidades de cada entidade que auxiliam no diagnóstico.

Autoimmune limbic encephalitis (AE) is an autoimmune-mediated inflammation typically affecting the medial temporal lobes and other limbic structures (cingulate gyrus, orbital cortex, and hypothalamus). It can be associated with underlying malignancy as a paraneoplastic syndrome. Nonparaneoplastic AE is a difficult disease to diagnose and often requires the collaboration of multiple modalities for effective diagnosis and treatment. We describe an interesting case of contactin-associated protein-like 2 antibody-associated nonparaneoplastic limbic encephalitis on fluorine-18 fluorodeoxyglucose positron emission tomography and magnetic resonance imaging.

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.

Highlights • The pattern of cortical atrophy is present throughout all anti-GAD phenotypes. • The radiomic features correctly classify anti-GAD patients versus healthy subjects. • The different neurological anti-GAD phenotypes should be considered as a continuum., Neurological disorders associated with anti-glutamic acid decarboxylase (GAD) autoimmunity are rare and include a variety of neurological syndromes: stiff-person syndrome, cerebellar ataxia or limbic encephalitis. The diagnosis remains challenging due to the variety of symptoms and normal brain imaging. The morphological MRI of 26 patients (T1-weighted and Fluid-attenuated inversion recovery (FLAIR)-weighted images) was analyzed at the initial stage of diagnosis, matched by age and sex to 26 healthy subjects. We performed a vertex-wise analysis using a generalized linear model, adjusting by age, to compare the brain cortical thickness of both populations. In addition, we used a voxel-based morphometry of cerebellum thickness obtained by CEREbellum Segmentation (CERES), as well as the hippocampus volumetry comparison using HIPpocampus subfield Segmentation (HIPS). Finally, we extracted 62 radiomics features using LifeX to assess the classification performance using a random forest model to identify an anti-GAD related MRI. The results suggest a peculiar profile of atrophy in patients with anti-GAD, with a significant atrophy in the temporal and frontal lobes (adjusted p-value

Background and purpose: The core manifestations of leucine-rich glioma-inactivated 1 (LGI1) autoantibody-mediated encephalitis are limbic encephalitis and faciobrachial dystonic seizures. Agrypnia excitata (AE) is a rare syndrome characterized by sleep–wake cycle disruption, autonomic hyperactivation and episodes of oneiric stupor. Only a few diseases are known to present with AE. An autoimmune etiology must be considered when accompanied by neuromyotonia. A case of anti-LGI1 encephalitis presenting with AE is reported. Methods: Detailed clinical, video-polysomnographic, laboratory, radiological and long-term follow-up assessments were performed. Results: A previously healthy 58-year-old man was referred for a rapidly progressive change in mental status, characterized by persistent drowsiness and confusion, accompanied by frequent episodes of unconscious gestures ranging from simple stereotyped movements to more complex actions mimicking various daily activities. Other symptoms included tachycardia, hyperhidrosis, mild hyponatremia, rare faciobrachial dystonic seizures, and a single generalized tonic–clonic seizure, but no neuromyotonia. Prolonged video-polysomnography excluded epileptic activity and showed continuous monomorphic slowing of background activity not consistent with a regular wakefulness or sleep state. A brain magnetic resonance imaging scan was unremarkable. Brain fluorodeoxyglucose positron emission tomography revealed hypermetabolism of the hippocampi, amygdala and basal ganglia. Anti-LGI1 antibodies were detected in the cerebrospinal fluid. The sleep disorder resolved progressively after starting immunotherapy. Conclusions: Agrypnia excitata can be a dominant, treatable manifestation of anti-LGI1 encephalitis. Oneiric stupor episodes are a useful clinical feature for establishing diagnostic suspicion and could provide a window to understanding the mechanisms behind some movement disorders in autoimmune encephalitis.

Autoimmune and paraneoplastic movement disorders are increasingly recognized as a result of improved methods in detecting antibodies directed against intracellular, membrane, and other antigens.1 High concentrations of anti-glutamic acid decarboxylase 65 (GAD65) antibodies are associated with several neurologic syndromes including stiff-person syndrome, epilepsy, limbic encephalitis, and cerebellar ataxia.2 Anti-GAD65-associated cerebellar ataxia is typically generalized with prominent gait disturbance and eye movement abnormalities.1 Limb ataxia is present in 60-70% of patients.3 Here we present 2 unusual cases of hemiataxia associated with high concentrations of anti-GAD65 antibodies.

Introduction LGI1 encephalitis is a rare form of limbic encephalitis, that was first recognised as a primary autoimmune phenomenon, and subsequently described in association with a limited number of malignancies.1 We report a novel case of LGI-1 encephalitis occurring concurrent to a high-grade papillary urothelial carcinoma. Case Presentation A previously well 72-year-old male presented to a rural hospital with a first episode generalised tonic-clonic seizure, confusion and progressive behavioural change. He was diagnosed with LGI-1 encephalitis, with positive CSF antibodies, and mesial temporal T2 hyperintensity on MRI brain. There was no response to first line treatment with steroids, intravenous immunoglobulin, and mycophenolate. Malignancy screening revealed a lesion within the upper pole of the left kidney, favoured to represent a transitional cell carcinoma. Biopsy demonstrated a low grade papillary urothelial carcinoma. The patient’s encephalopathy continued to worsen over a period of months, despite ongoing immunosuppression. He underwent a left nephrouretectomy, and histology demonstrated a high-grade papillary urothelial carcinoma. Subsequent to this, there was improvement in cognition and behaviour. Psychotropic and immunosuppressive medications were slowly weaned. At 9-month follow-up, the patient has returned close to baseline function, and has been clinically stable off all immunosuppressive treatment. Conclusions LGI-1 encephalitis has previously been described in association with thymoma, lymphoma, teratoma, and more recently with lung and prostate cancer.2 3 We believe our case is the first report of association between LGI-1 encephalitis and high grade papillary urothelial carcinoma. References van Sonderen A, et al. Anti- LGI1 encephalitis. NeurologyOct 2016;87(14):1449–1456. Navalli D, Mutalik NR, Jayalakshmi G. Leucine-rich glioma-inactivated protein 1 antibody-positive limbic encephalitis in a patient with adenocarcinoma of prostate: a case report. Ann Indian Acad Neurol Jan-Mar 2019:22(1):121–122. Virupakshaiah A, Dalakas M, Desai N, Mintzer S, Ratliff J. A report on LGI1 encephalitis in association with squamous cell carcinoma of the lung. Neurology Apr 2019;92(15 Supp):2.2–028.

Sjogren’s syndrome (SS) is an autoimmune disorder characterized by lymphocytic and plasma cell infiltration of exocrine glands, resulting in dry mouth and keratoconjunctivitis sicca. The clinical symptoms may range from mucosal dryness to more systemic complaints. We report a 42-year-old man presenting with rapid cognitive decline and memory impairment for 2 months. Magnetic resonance imaging of the cranium revealed abnormal signals at the bilateral medial temporal lobe and hippocampal region. The autoimmune panel and paraneoplastic antibodies were negative. The patient was labeled as a case of primary SS based on the vasculitis profile and pathological examination of lip biopsy. This case illustrates a rare, heralding manifestation of SS as limbic encephalitis.

Antibodies targeting the 65-kilodalton isoform of glutamic acid decarboxylase (GAD65) are implicated in several autoimmune neurologic disorders.1 Anti-GAD65 antibodies (GAD65-Abs) can be seen in healthy individuals, highlighting the importance of interpreting their significance in the appropriate clinical context.1 Classic neurologic presentations include stiff-person syndrome, cerebellar ataxia, limbic encephalitis, epilepsy, myelopathy, other brainstem manifestations, and extrapyramidal symptoms.1–3 A few cases of focal myoclonus have been described.2 There is one previous report of palatal myoclonus with normal brain MRI.4 We report a patient with GAD65-Abs with relapsing diplopia, cerebellar syndrome, and palatal myoclonus with hypertrophy of the inferior olivary nuclei (ION) seen on 1.5T MRI and a dentato-rubro-olivary pathway lesion on 7T MRI.

The development of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is often associated with neoplasia or infectious diseases as antibodies against neurons or synaptic proteins surface. A 30-year-old male patient was admitted to our department because of neurocognitive symptoms, particularly memory difficulties which had appeared a year prior and since then had been increasing. He had a medical history of smoking and hypertension. On examination, there were no focal neurological deficits. However, neuropsychological tests confirmed a lack of concentration and short-term memory impairment. Brain magnetic resonance imaging (MRI) and electroencephalography (EEG) remained unremarkable. Cerebrospinal fluid (CSF) analysis revealed a low lymphocytic pleocytosis without oligoclonal bands. Serum testing for human immunodeficiency virus (HIV) was positive with 420,000 HIV-1-RNA copies/ml. On a more detailed physical examination, a large number of purple patches were found on the entire body, which a biopsy confirmed to be Kaposi sarcoma (KS). A positive serum and CSF NMDA receptor antibody titer (serum 1:280; CSF 1:8) confirmed the diagnosis of an AIDS-associated anti-NMDA receptor encephalitis; therefore, we treated him with antiretroviral and immunosuppressive therapy. After 12 months, the KS lesions faded and the cognitive deficits improved slightly. Our case highlights that a detailed clinical examination and searching for neoplasia and/or an infection are helpful, though often neglected, tools for detecting an anti-NMDA receptor 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.

Background Immune checkpoint inhibitors have revolutionized the treatment of many cancers, including melanoma, non-small cell lung cancer, and renal cell carcinoma. These therapeutics increase the activity of T cells against neoplastic cells, although the immune response generated also has the potential to target normal cells, resulting in immune related adverse events (irAEs). Most irAEs occur outside of the nervous system, but cases of limbic encephalitis, hypophysitis, optic neuritis, and pseudoprogression have been reported. Case Description Here, we present a case of an intracranial irAE after neoadjuvant stereotactic radiosurgery and craniotomy for resection of a left parietal lobe metastasis. The patient presented with headache, right-sided apraxia, and a pronator drift 2 weeks after surgery. Imaging findings were suggestive of an intracranial abscess. The lack of fever, normal white blood cell count, and benign clinical appearance in the setting of combination nivolumab and ipilimumab therapy argued in favor of an irAE, however. After initiation of dexamethasone, the neurologic deficits resolved and the magnetic resonance imaging of the brain normalized over 7 weeks. Conclusions This is the first report of an acute surgical-site irAE after stereotactic radiosurgery and craniotomy in a patient receiving nivolumab and ipilimumab. These immune-mediated responses can be treated with corticosteroids and close observation.

Hashimoto's encephalopathy (HE) is a steroid-responsive autoimmune encephalopathy associated with Hashimoto thyroiditis. We herein report a case of HE manifesting “smoldering” limbic encephalitis with persisting symptoms and abnormalities on examinations. Although our patient experienced partial clinical remission after treatment, hippocampal hypermetabolism on [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) and subclinical seizures on video electroencephalography persisted. Hypermetabolism on FDG-PET was improved by additional prednisolone therapy. Thus, as with other autoimmune limbic encephalitis cases, HE can take a course of “smoldering” encephalitis. FDG-PET and electroencephalogram findings can reflect the disease activity degree in such patients, although with certain neurophysiological and biochemical distinctions.

A 7‐year‐old neutered female domestic shorthaired cat born in Poland and then moved to Japan presented to the local clinic with recent onset of convulsive cluster seizures and status epilepticus. Magnetic resonance imaging revealed bilateral swelling of the hippocampus with T2 hyperintensity and contrast enhancing image, suggesting hippocampal necrosis. The cat completely recovered after treatment with antiepileptic drugs (AED) and administration of prednisolone (1 mg/kg PO q24h for 4 days and tapered). However, cluster seizures reoccurred and developed into status epilepticus despite increasing doses of AED. Although the convulsions were resolved by other AEDs, stupor and renal failure developed, and the cat was euthanized. Pathological findings were consistent with hippocampal necrosis. Immunological analysis for leucine‐rich glioma inactivated 1 (LGI1) autoantibodies was negative, but antibodies against DCC (deleted in colorectal carcinoma) known as netrin‐1 receptor were found. This report describes a case of feline autoimmune limbic encephalitis and hippocampal necrosis that were presumably associated with DCC autoantibodies.

A 12-year-old girl was admitted to the authors’ hospital due to muscle weakness, gait disturbance, dysarthria, dysphagia, and diplopia. She experienced prodromal fever 10 days before admission. On examination, deep tendon reflex was absent in the extremities, and nerve conduction velocity was decreased in the ulnar nerve. She was diagnosed with Guillain-Barré syndrome (GBS). Despite steroid pulse therapy following administration of intravenous high-dose γ-globulin, clinical manifestations remained unchanged. Therefore, plasma exchange was performed on day 10 of the illness. The titer of serum Mycoplasma immunoglobulin M level was increased. Immunological testing was positive for serum anti-galactocerebroside C antibody. On day 18 of the illness, however, she developed generalized convulsion. Brain magnetic resonance imaging revealed high intensity in the medial temporal lobes, including the hippocampus and thalamus on T2-weighted intensity imaging, which was consistent with limbic encephalitis. Further immunological tests revealed positivity for anti-N-methyl-D-aspartate-type glutamate receptor antibody in the cerebrospinal fluid. She was treated with additional plasma exchange; however, she exhibited residual manifestations including short-term memory disorder, emotional incontinence, and convulsions. This article describes a notable case of limbic encephalitis following GBS associated with prodromal Mycoplasma infection. It is interesting that autoimmune encephalopathy is concomitant with autoimmune polyneuropathy subsequent to Mycoplasma infection.

Introduction: Paraneoplastic limbic encephalitis is a rare disease, usually associated with small cell lung cancer. Case report: We report in this publication the cases with different age brackets, who presented with various neurological symptoms such as repetitive seizures or anterograde amnesia. Cerebral CT-scan, cerebral MRI and anti onco-neural paraneoplastic antibodies were suggesting the diagnosis of paraneoplastic limbic encephalitis. Etiological exploration lead to the diagnosis of locally advanced small cell carcinoma of the lung. We started rapidly a curative protocol associating chemotherapy and sequential thoracic radiotherapy. Conclusions: we insist on the diversity of the imaging findings, immunological analyses and outcome on treatment of this entity. Prognostic impact remains also unclear. Keywords: Limbic encephalitis, Paraneoplastic, Small cell carcinoma, Antibodies, Magnetic resonance imaging

Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis, was first reported by Lai et al. The AMPAR antibodies target against extracellular epitopes of the GluA1 or GluA2 subunits of the receptor. AMPARs are expressed throughout the central nervous system, especially in the hippocampus and other limbic regions. Anti-AMPAR encephalitis was more common in middle-aged women and most patients had an acute or subacute onset. Limbic encephalitis, a classic syndrome of anti-AMPAR encephalitis, was clinically characterized by a subacute disturbance of short-term memory loss, confusion, abnormal behavior and seizure. Magnetic resonance imaging often showed T2/fluid-attenuated inversion-recovery hyperintensities in the bilateral medial temporal lobe. For suspected patients, paired serum and cerebrospinal fluid (CSF) testing with cell-based assay were recommended. CSF specimen was preferred given its higher sensitivity. Most patients with anti-AMPAR encephalitis were complicated with tumors, such as thymoma, small cell lung cancer, breast cancer, and ovarian cancer. First-line treatments included high-dose steroids, intravenous immunoglobulin and plasma exchange. Second-line treatments, including rituximab and cyclophosphamide, can be initiated in patients who were non-reactive to first-line treatment. Most patients with anti-AMPAR encephalitis showed a partial neurologic response to immunotherapy.

Paraneoplastic limbic encephalitis (PLE) is one of paraneoplastic neurological syndrome (PNS). We herein report a case of PLE due to lung squamous cell carcinoma. A 80-year-old woman visited because of several neurological symptoms. Brain magnetic resonance imaging revealed hyperintense signals at the splenium of the corpus callosum, suggesting limbic encephalitis. Chest X-ray and computed tomography showed a 17 × 14 mm tumor in the left lung field, suggesting lung cancer. Surgical examination revealed T1bN0M0 lung squamous cell carcinoma. She died 50 days after surgery due to the rapid progression of encephalitis. PLE is an extremely rare disorder, and even a case in the early stage of cancer shows poor prognosis. We should doubt a possibility of PLE, and detailed brain examination should be performed in case of consciousness disorder with rapid progression in the cancer patient.

The diagnosis of leptomeningeal metastases is sometimes difficult when the cytology of cerebrospinal fluid is negative. We report a rare case of leptomeningeal metastases that required differentiation from paraneoplastic limbic encephalitis. A 67-year-old man with extensive-stage small cell lung cancer was admitted for a sudden decrease in the level of consciousness. He suffered memory disturbances that began the day before admission. Diffusion-weighted and fluid-attenuated inversion recovery images of brain magnetic resonance imaging (MRI) showed bilateral symmetric areas of hyperintensity in the hippocampus, amygdala, insular cortex, and medial temporal lobe; contrast enhancement was positive. Cytology of the cerebrospinal fluid (CSF) was negative. Anti-N-methyl-d-aspartate receptor antibody and herpes simplex virus DNA were not detected in the CSF. Paraneoplastic Limbic encephalitis was suspected due to his symptoms and brain MRI scan. The patient developed generalized seizures after admission. High-dose methylprednisolone and intravenous immune globulin were administered, but his condition did not improve. Uncontrollable seizures persisted and he died in the hospital at day 13. Autopsy revealed leptomeningeal metastasis and invasion of cancer cells into the limbic system. Contrast-enhanced MRI should be performed even if limbic encephalitis is suspected, and leptomeningeal metastases should be suspected if the lesions are enhanced.

Background Limbic encephalitis (LE), a variant of autoimmune encephalitis, is inflammation of the limbic system of the brain. The disorder presents with subacute impairment of short-term memory, psychiatric manifestations, confusion and seizures. “Seronegative LE” is a challenging diagnosis in the absence of well-characterized autoantibodies. Case presentation A 33-year-old Kuwaiti woman with no relevant past history presented with subacute progressive amnesia of 6-month duration. Magnetic resonance imaging (MRI) showed bilateral hyperintensity of the limbic structures. An extensive workup of the blood and cerebrospinal fluid (CSF) failed to identify paraneoplastic or autoimmune antibodies. The diagnosis of seronegative LE was made, and immunotherapy was initiated, with improvement in cognitive function. Conclusion Seronegative LE is a challenging diagnosis. Inability to detect autoantibodies, especially early in the disease course, should not rule out the diagnosis of autoimmune encephalitis. Early diagnosis and treatment with immunotherapy may prevent irreversible brain damage.

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).

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.

Anti Ma 2 encephalitis is an autoimmune encephalitis, usually paraneoplastic, characterized by isolated or combined limbic, diencephalic, or brainstem dysfunction. Limbic encephalitis (LE) is the most common manifestation. Anti-Ma2 LE can also be manifested as a pure psychiatric disturbance associated or not with hypokinesia. Other patients exhibit excessive daytime sleepiness, vertical ophthalmoparesis, or both associated with LE, due to diencephalic and/or upper brainstem involvement. These cases are challenging and demand extensive work-up for differential diagnosis.

OBJECTIVE This study was undertaken to describe a novel biomarker of germ cell tumor and associated paraneoplastic neurological syndrome (PNS). METHODS Archival sera from patients with germ cell tumor-associated PNS were evaluated. We identified a common autoantigen in a human testicular cancer cell line (TCam-2) by Western blot and mass spectrometry. Its identity was confirmed by recombinant-protein Western blot, enzyme-linked immunosorbent assay (ELISA), and cell-based assay. Autoantibody specificity was confirmed by analyzing assorted control sera/cerebrospinal fluid. RESULTS Leucine zipper 4 (LUZP4)-immunoglobulin G (IgG) was detected in 28 patients' sera, 26 of whom (93%) were men. The median age at neurological symptom onset was 45 years (range = 28-84). Median titer (ELISA) was 1:300 (1:50 to >1:6,400, normal value

Anti-LGI1 encephalitis is an autoimmune encephalitis with antibodies against leucine-rich glioma-inactivated 1 (LGI1), first described in 2010. It is a non-frequent and poorly understood entity that represents the second most frequent cause of autoimmune encephalitis. This entity is characterized by the presence of limbic encephalitis, hyponatremia, and faciobrachial dystonic seizures. Herein, we present the case of a male patient with an onset of epileptic seizures (generalized tonic-clonic seizure), and involuntary dystonic movements that affect the right side of his face and right upper limb associated with mental disorder, and affectation of higher functions. The electroencephalogram showed continuous generalized slowing of the background activity. The brain magnetic resonance imaging showed signal hyperintensity at the level of both mesial temporal lobes and hippocampi and in the head of the right caudate nucleus. Anti-thyroglobulin antibodies were positive, and he was initially diagnosed as Hashimoto's encephalopathy (HE). However, the response to corticosteroids was not completed as it is usually observed in HE. For that, antibodies for autoimmune encephalitis were tested, and the anti-LGI1 antibodies were positive in serum and cerebrospinal fluid. HE is an important differential diagnosis to consider. Furthermore, the presence of Anti-thyroglobulin antibodies should not be taken as the definitive diagnostic criteria, since these antibodies could be associated with other autoimmune encephalopathies, which include in addition to anti-LGI1, anti-NMDA and anti-Caspr2.

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. 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. 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. 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.

Limbic encephalitis is a rare paraneoplastic neurological syndrome usually associated with small cell lung cancers, testicular and breast cancers or B-cell lymphomas. We herein report the first patients with paraneoplastic limbic encephalitis associated with HU antibodies and anaplastic T-cell lymphoma.

Paraneoplastic neurological syndromes (PNS) are immune-mediated disorders that can affect any part of the nervous system, including the retina, spinal cord, peripheral nerve, and neuromuscular junction. These disorders manifest with a variety of neurological syndromes, the most characteristic being limbic encephalitis, cerebellar degeneration, or sensory neuronopathy. They frequently occur in patients with cancer and are thus considered paraneoplastic. Most PNS are characterized by detection of autoantibodies, in serum and cerebrospinal fluid, which target a variety of intracellular neuronal antigens, such as Hu or Yo proteins. These antibodies are markers of the presence of a tumor, given that they can also be found in a proportion of patients with tumor but without neurological symptoms, and they are not considered pathogenic. It is thought that PNS are caused by an anti-tumor immune response, mainly mediated by cytotoxic T cells, which is directed against neuronal antigens that are also ectopically expressed by tumor cells. Response of neurological symptoms to treatment depends on the neurological syndrome, associated cancer, and neuronal antibody. However, overall, patients with PNS associated with antibodies against intracellular antigens show poor response to cancer treatment and immunotherapies, likely due to irreversible T-cell-mediated neuronal damage.

We report the case of a 55-year-old man presenting pseudopsychiatric behavior disorders of subacute-onset. MRI showed a FLAIR (fluid-attenuated inversion recovery) hyperintensity in the left hippocampus. The diagnosis of limbic encephalitis was raised, and the patient was referred for an 18F-FDG PET/CT. PET/CT depicted an increased uptake of the left mesiotemporal structures and also an increased uptake of both cerebellum and striatal areas. This pattern was compatible with an anti-leucine-rich glioma-inactivated 1 antibody encephalitis that was later confirmed.

The spectrum of anti-contactin-associated protein-like 2 (CASPR2) antibody-associated disease is expanding and the involvement of cerebellum was reported in the past few years. We report a 45-year-old male with chronically progressive cerebellar ataxia. CASPR2 antibodies were detected in his serum and cerebellar atrophy was observed on MRI. His symptoms improved prominently with steroids and intravenous immunoglobulins. 23 cases with CASPR2 antibodies and cerebellar ataxia were identified from previous publications. Most of patients showed acute or subacute onset with other typical presentations of anti-CASPR2 antibody-associated disease, such as limbic encephalitis. Immunotherapy was effective in the majority of patients.

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Limbic encephalitis is an inflammatory process involving the limbic structures of the brain, manifested with short-term memory deficits, confusion, depression and seizures. It is usually a paraneoplastic condition but it may also appear as a nonparaneoplastic syndrome. Patients with this condition may exhibit a variety of antibodies in their serum or/and cerebrospinal fluid targeting basement membrane components that bind to a variety of neurotransmitter receptors such as α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and GABA B and proteins associated to the ion channels such as LGI1, Caspr2 or intracellular components. Flurodeoxyglucose PET/computed tomography usually demonstrates increased uptake in the limbic structures, and it may reveal the site of the primary tumor. Treatment consists of tumor removal if possible. Symptomatic treatment includes steroids, gamma immune globulin, plasma exchange, immunosuppressive therapies and anti-epileptic drugs. Prognosis is better when it is associated with antibodies against basement membrane rather than intracellular antibodies.

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.