GABABR-Mediated Paraneoplastic Limbic Encephalitis Due To Thymic Small Cell Carcinoma.

We report the case of a 55-year-old male who presented with several weeks of seizures, agitation, progressive confusion, and receptive aphasia. CSF showed a monocytic pleocytosis and tested positive for GABAB receptor autoantibodies. Pathological examination of an excisional mediastinal lymph node biopsy showed thymic small cell carcinoma, supporting a diagnosis of paraneoplastic limbic encephalitis (PLE). PLE is a subtype of limbic encephalitis and is associated with an array of autoantibodies. Neurologic symptoms related to PLE may precede the detection of the primary cancer. Recognition of the constellation of clinical features of limbic encephalitis should prompt initiation of diagnostic testing for this condition as well as evaluation for an underlying malignancy. A review of the literature reveals that this is the first case report of a patient with thymic small cell cancer presenting with PLE.

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

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

Occupation-Associated Fatal Limbic Encephalitis Caused by Variegated Squirrel Bornavirus 1, Germany, 2013.

Limbic encephalitis is commonly regarded as an autoimmune-mediated disease. However, after the recent detection of zoonotic variegated squirrel bornavirus 1 in a Prevost's squirrel (Callosciurus prevostii) in a zoo in northern Germany, we retrospectively investigated a fatal case in an autoantibody-seronegative animal caretaker who had worked at that zoo. The virus had been discovered in 2015 as the cause of a cluster of cases of fatal encephalitis among breeders of variegated squirrels (Sciurus variegatoides) in eastern Germany. Molecular assays and immunohistochemistry detected a limbic distribution of the virus in brain tissue of the animal caretaker. Phylogenetic analyses demonstrated a spillover infection from the Prevost's squirrel. Antibodies against bornaviruses were detected in the patient's cerebrospinal fluid by immunofluorescence and newly developed ELISAs and immunoblot. The putative antigenic epitope was identified on the viral nucleoprotein. Other zoo workers were not infected; however, avoidance of direct contact with exotic squirrels and screening of squirrels are recommended.

Possible autoantibody-negative limbic encephalitis after anterior temporal lobectomy for hippocampal sclerosis.

PURPOSE: Amnestic syndromes are acknowledged to be associated to bilateral hippocampal damage. MATERIALS AND METHODS: We briefly report the case of a young man who underwent anterior left temporal lobectomy for a medically refractory temporal lobe epilepsy due to hippocampal sclerosis with an excellent seizure and neuropsychological outcome. Approximately 10 years later, he presented with a subacute severe global amnesia and neuroimaging findings of a damage involving the contralateral mesial temporal lobe structures. RESULTS: A diagnosis of a possible autoimmune encephalitis was made. CONCLUSIONS: Due to its peculiarities (compared with other cases of bilateral temporal lesions, the damage occurred on two distinct occasions), this case might contribute to shed light on the issue of the possible contralateral reorganization of memory processes subserved by the mesial temporal lobe structures chronically involved in epileptogenesis.

Retrospective study of paraneoplastic neurological syndromes in a Chinese Han population from Shandong, East China.

OBJECTIVE: To analyze the clinical features, diagnostic strategies and therapeutic methods associated with paraneoplastic neurological syndromes. METHODS: A retrospective study of paraneoplastic neurological syndromes was performed at a single center in Shandong, East China. The medical records and follow-up data of 28 patients were intensively reviewed between February 2011 and December 2014. RESULTS: Twenty-four (85.7%) patients experienced subacute or chronic onset of disease, and the most common symptoms reported were mild myasthenia and paresthesias. Twenty-five (89.3%) patients presented nervous system lesions prior to occult tumors, and the median time frame between paraneoplastic neurological syndromes onset and the diagnosis of a tumor was 15 weeks. Sensorimotor neuropathy, Lambert-Eaton myasthenic syndrome and limbic encephalitis were the three most common neurological syndromes reported. Elevated serum tumor markers were observed in 44.0% of patients, while 40.7% of patients were positive for onconeural antibodies. Tumors were detected in 21 (75.0%) patients after repeated whole-body screening, and lung carcinomas were the most common primary tumor detected. Seventeen patients received anti-tumor or immunological therapy, and clinical symptoms were relieved in 13 (76.5%) of these patients. CONCLUSIONS: In the majority of paraneoplastic neurological syndromes patients, the onset of disease is subacute or chronic with mild clinical symptoms. Nervous system lesions usually occur prior to occult tumors with complicated and various clinical manifestations. Neither tumor markers nor onconeural antibodies exhibit a high rate of occurrence, while repeated whole-body screening is helpful in identifying occult tumors. Early diagnosis and treatment are crucial to these patients.

Immune-mediated neurological manifestations of dengue virus- a study of clinico-investigational variability, predictors of neuraxial involvement, and outcome with the role of immunomodulation.

INTRODUCTION: Our aim was to study dengue-related immune-mediated neurological complications (IMNC) during the recent epidemic. MATERIALS AND METHODS: This was a cross-sectional observational study of 79 IMNC cases from 1627 laboratory confirmed dengue cases from January 2015 to January 2016 and their follow-up for 3 months. According to the World Health Organization, cases were categorized into those having dengue fever (DF), and those having a severe syndrome that includes dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Laboratory as well as clinicoradiological data, the predictors of outcome, and the role of immunomodulation in determining the final result were analyzed. RESULTS: Out of the 1627 confirmed dengue cases, 14.6% developed neurological complications and only 4.86% cases had IMNC. Among the IMNC seen, the majority of the patients had the onset of their manifestations in the subacute (7-30 days) latency period; however, there was no mortality seen. We found Miller Fisher syndrome (MFS), limbic encephalitis, and immune-mediated cerebellar demyelination (IMCD) as the new findings in the IMNC spectrum. Patients with DF were more prone to developing brachial plexus neuritis and polyneuritis cranialis, whereas those patients with a severe syndrome were more commonly associated with Guillain-Barre syndrome (GBS). Significant (P < 0.001) predictors of central nervous system involvement were anemia, an elevated hematocrit, and the presence of DSS, whereas patients with a higher mean body temperature, DF, and elevated hematocrit were more prone to developing peripheral nervous system manifestations. The platelets counts and the hemoglobin levels had a negative correlation whereas the hematocrit value, the mean body temperature, and the alanine aminotransferase levels had a moderately significant positive correlation for the development of IMNC. The immunomodulatory therapy (IMT), if initiated after fever abatement led to a significant clinically favorable outcome at 3 months, especially in patients with GBS, polyneuritis cranialis, and brachial plexus neuritis. CONCLUSION: The spectrum of IMNC is vast and may include MFS, limbic encephalitis and IMCD. Early initiation of IMT, in the presence of significant predictors, may reduce the IMNC-related morbidity.

Encephalopathy with upper body hypertonia and myoclonus in patient with systemic lupus erythematosus and anti-CASPR2.

Systemic lupus erythematosus (SLE) may involve the nervous system but there are no specific biomarkers of neuroSLE. Limbic encephalitis has been rarely associated with SLE. We present a case of a 22-year-old black woman where typical SLE psychosis evolved to an encephalopathy with atypical features, normal MRI, electroencephalogram slowing and frontal and occipito-temporal hypometabolism on fluorodeoxyglucose positron emission tomography (FDG PET).Memory deficits, bizarre behaviour, psychosis, neuromyotonia and movement disorders have been described in autoimmune central nervous system disorders and associated with specific antibodies. Brain MRI may be normal and cortical brain hypometabolism on FDG PET scans has been reported. We have not found any report of limbic encephalitis or other SLE neurological manifestation associated to positive titres of anti-CASPR2 antibodies and this may warrant systematic investigation. In the rare cases of limbic encephalitis associated with SLE no specific antibodies were documented. Anti-CASPR2 antibodies have been associated not only with limbic encephalitis but also with neuromyotonia and Morvan syndrome. Although our patient had a specific pattern of tone abnormalities with an impressive cervical and upper limb hypertonicity and flaccid lower limbs, no myotonic discharges were found. We did not find any association between myoclonus and anti-CASPR2 antibodies. We cannot exclude that a non determined autoantibody could have played a role; however, clinical and FDG PET improvement supports an antibody-mediated injury, in this case of neuroSLE.

Anti-N-methyl-d-aspartate receptor limbic encephalitis associated with mature cystic teratoma of the fallopian tube.

Anti-N-methyl-d-aspartate receptor (NMDAR) limbic encephalitis is the most common form of paraneoplastic encephalitis that is associated with teratomas. Because tumor removal leads to better clinical outcomes, it is essential to reveal the location of the teratomas. This is the first reported case of anti-NMDAR encephalitis associated with teratoma of the fallopian tube. Salpingo-oophorectomy improved neurological symptoms and immunohistochemical examinations indicated the expression of NMDAR on neuroglial cells within the fallopian tube teratoma. Teratomas of the fallopian tube cause anti-NMDAR encephalitis; the imaging analysis and exploratory laparoscopies of the fallopian tube as well as of the ovary should be considered. Surgical removal of both fallopian tubes and ovaries with a normal appearance should be considered for patients in whom immunotherapy is not effective.

[Gabab paraneoplastic encephalitis : about a clinical case]. / Encéphalite limbique paranéoplasique a anticorps Anti-gabab.

The paraneoplastic limbic encephalitis is a rare disease. It is caused by the presence of autoantibodies creating an inflammatory reaction of the predominant brain parenchyma in the meso-temporal lobe and in other parts of the limbic system. Its presence requires looking for an underlying tumour. The management of this paraneoplastic syndrome includes an immunosuppressive therapy in addition to the treatment of the underlying tumour. However, the management of this disease is not yet standardized.

L'encéphalite limbique paranéoplasique est une maladie rare. Elle est causée par la présence d'auto-anticorps créant une réaction inflammatoire du parenchyme cérébral prédominant au niveau du lobe méso-temporal et dans d'autres parties du système limbique. Sa présence impose la recherche d'une tumeur sous-jacente. Le traitement du syndrome paranéoplasique comprend des immunosuppresseurs en plus du traitement de la tumeur sous-jacente. Cependant, la prise en charge de cette pathologie n'est pas encore bien codifiée.

Therapeutic plasma exchange as a steroid-sparing therapy in a patient with limbic encephalitis due to antibodies to voltage-gated potassium channels.

Autoantibodies to the voltage-gated potassium channel (VGKC) complex cause a spectrum of non-paraneoplastic neurologic syndromes including limbic encephalitis (LE). We report a case of a man with LE who underwent a course of therapeutic plasma exchange (TPE) in addition to other immunomodulatory therapies and experienced sustained clinical resolution of his symptoms. This report adds to the existing literature supporting TPE in cases of LE due to VGKC complex autoantibodies.

Paraneoplastic Limbic Encephalitis Associated with Adenocarcinoma of Lung.

PURPOSE: Paraneoplastic limbic encephalitis (PLE) is a rare, immune-mediated entity. We present an unusual case of a patient who has double cancers and two different paraneoplastic neurological syndromes. CASE REPORT: A 58-year-old gentleman has histories of adenocarcinoma of lung and malignant thymoma associated with myasthenia gravis, which underwent surgery and chemotherapy 3 years ago. This time, he presented to our ward with rapidly progressive memory decline and myoclonic jerks in his limbs for two weeks. Magnetic resonance imaging (MRI) of brain showed increased signal intensity over bilateral mesial temporal regions on T2 Fluid Attenuated Inversion Recover (FLAIR) series. Chest computed tomography showed cancer recurrence. He received steroid pulse therapy firstly and right lung lower lobe lobectomy later. Pathology report of the tumor was recurrent adenocarcinoma. After the immunotherapy and tumor resection, his mentality improved gradually. Six months later, brain MRI showed resolution of bilateral temporal hyperintensity with residual mesial temporal atrophy. CONCLUSION: From our case, we would like to emphasize that paraneoplastic limbic encephalitis should be considered among the differential diagnosis of rapidly progressive dementia associated with myoclonus, along with other neurodegenerative diseases. Depending on its underlying malignancy, the cognitive impairment may be substantially reversible, despite atrophy of mesial temporal lobes.

Paraneoplastic encephalitis.

The first reports of encephalitis associated with cancer date to the 1960s and were characterized by clinical and pathologic involvement of limbic areas. This specific association was called limbic encephalitis (LE). The subsequent discovery of several "onconeural" antibodies (Abs), i.e., Abs targeting an antigen shared by neurons and tumor cells, supported the hypothesis of an autoimmune paraneoplastic etiology of LE and other forms of rapidly progressive encephalopathy. Over the past 20 years, similar clinical pictures with different clinical courses have been described in association with novel Abs-binding neuronal membrane proteins and proved to be pathogenic. The most well-known encephalitis in this group was described in 2007 as an association of a complex neuro-psychiatric syndrome, N-methyl-d-aspartate (NMDA) receptor-Abs, and ovarian teratoma in young women. Later on, nonparaneoplastic cases of NMDA receptor encephalitis were also described. Since then, the historical concept of LE and Ab associated encephalitis has changed. Some of these occur in fact more commonly in the absence of a malignancy (e.g., anti-LG1 Abs). Lastly, seronegative cases were also described. The term paraneoplastic encephalitis nowadays encompasses different syndromes that may be triggered by occult tumors.

Limbic encephalitis: a clinical-radiological comparison between herpetic and autoimmune etiologies.

BACKGROUND: Herpetic (HE) and autoimmune (AE) encephalitis share clinical and radiological features. We compared both types of encephalitis with the aim of making a differential clinical-radiological pattern. MATERIALS AND METHODS: All cases with a clinical diagnosis of encephalitis who attended our hospital between 1999 and 2012 were reviewed. We selected those cases with positive polymerase chain reaction for herpes simplex virus 1 (HSV-1) in the cerebrospinal fluid (CSF), and those with antineuronal antibodies or paraneoplastic etiology. We compared epidemiological, clinical, CSF, electroencephalographic and radiological findings. RESULTS: Twelve patients with positive polymerase chain reaction for HSV-1, and 10 patients with antineuronal antibody or paraneoplastic etiology were found. The only features found exclusively in one group were the presence of psychiatric symptoms and tumors in AE. Acute onset of symptoms, fever and aphasia were more frequent in HE, which showed higher level of proteins and erythrocyte count in CSF. Neuroimaging was abnormal in all cases of HE, but only in 60% of AE. Insular and diffuse temporal lobe involvement and absence of basal ganglia involvement were more frequent in HE, and mesial temporal involvement in AE. The highest diagnostic values for differentiating HE from AE were the association of acute onset of symptoms and fever (sensitivity 0.92, specificity 1), and the absence of basal ganglia involvement (sensitivity 0.82, specificity 1). CONCLUSIONS: There are few differences between HE and AE. Psychiatric symptoms and association with tumors were unique for AE. Acute onset with fever and absence of basal ganglia involvement in magnetic resonance imaging support a diagnosis of HE.

Prostate cancer may trigger paraneoplastic limbic encephalitis: a case report and a review of the literature.

We present a case of a previously healthy and active 64-year-old man who experienced a rapid neuropsychiatric decline. All tests for metabolic causes, neuroinfection, intracranial infarction or tumor were negative. By the means of magnetic resonance imaging, electroencephalography and the anti-Hu antibody test the patient was diagnosed with paraneoplastic limbic encephalitis related to prostate cancer. The patient died within 6 months. We review the literature on prostate cancer-related paraneoplastic limbic encephalitis. High-risk prostate cancer can trigger paraneoplastic limbic encephalitis, a rapidly progressive neurological syndrome with a bad prognosis.

[Lung cancer associated paraneoplastic limbic encephalitis: an analysis of 7 cases].

OBJECTIVE: To analyze the clinical features, diagnosis and treatment of lung cancer associated paraneoplastic limbic encephalitis (PLE). METHODS: The clinical data of 7 cases of patients with lung cancer associated PLE out of 8927 patients of lung cancer from January 2000 to May 2010 was analyzed retrospectively. All the patients were male, aging from 41 to 54 years with a mean of 48 years. The data including history, physical examination, laboratory tests, diagnosis, treatment and follow-up were collected and analyzed. RESULTS: All the 7 patients had smoking history. All 7 patients had varying short-term memory loss, 6 had epilepsy, 4 had different degrees of mental disorders, and 2 had syndrome of inappropriate secretion of antidiuretic hormone. Malignancies were screened and detected by chest X-ray or CT scan, while the pathological diagnoses were obtained through biopsy or transbronchial needle aspiration through electronic bronchoscope (5/7), biopsy of supraclavicular lymph nodes (1/7) and open pulmonary lobectomy (1/7). The pathological diagnosis included small cell lung cancer in 6 cases, adenocarcinoma of lung in 1 case. During the follow-up, 1 patient was lost, and the mean time of follow-up of the remaining 6 patients was about 11.5 months (ranged from 4 to 21 months). Four patients received early immunosuppressive treatment in terms of corticosteroids, only slight relief of neurological symptoms was seen in 2 patients. However, after chemotherapy (6/6), radiation (3/6), or surgical removal of the tumor (1/6), complete remission (3/6, with negative anti-Hu antibody) or partial remission (3/6, 2 of whom with positive anti-Hu antibody) of neurological symptoms were observed. Till October 2010, 3 patients with poorer tumor stag died ( survival were 4, 10, and 14 months respectively), while the other 3 patients with negative anti-Hu antibody and relative better tumor stag were still in the follow-up (the period were 5, 15, and 21 months). CONCLUSIONS: PLE is a rare disease. In comparison with immunosuppressive therapy, chemotherapy, radiation or surgical removal of the tumor could provide better remission of the neurological symptoms. Positive serum anti-Hu antibody, poorer tumor stag, and together with poorer response to treatments seem to indicate a poorer prognosis.

Relapsing polychondritis presenting with sero-negative limbic encephalitis.

The presented case highlights a rare instance of relapsing polychondritis (RP) manifesting as seronegative limbic encephalitis, an uncommon neurological complication. A 70-year-old female patient with a history of RP-related inflammation, along with neuropsychiatric symptoms, was diagnosed through multidisciplinary collaboration. Swift administration of steroid therapy, followed by azathioprine, led to remarkable physical and cognitive recovery. This case emphasises the importance of a multidisciplinary approach in diagnosing and treating complex autoimmune disorders with neurological manifestations.

Case Report: Anti-mGluR5 antibody-negative Ophelia syndrome with failed lymph node biopsy due to steroid therapy.

Ophelia syndrome is paraneoplastic limbic encephalitis (PLE) with Hodgkin lymphoma. Some Ophelia syndrome patients have been reported as testing positive for anti-metabotropic glutamate receptor 5 (mGluR5) antibodies. However, we experienced a case of anti-mGluR5 antibody-negative Ophelia syndrome. The type of onset, neurological symptoms, and imaging as well as electroencephalographic findings were like previous reports except for a normal cell count in cerebrospinal fluid (CSF). Unfortunately, a lymph node biopsy failed and could not diagnose the patient before death because steroid treatment for limbic encephalitis had shrunk lymph nodes. We believe it is essential to accumulate cases of this syndrome and clarify the association between PLE and Hodgkin lymphoma so chemotherapy can be initiated even if malignant lymphoma cannot be pathologically proven or when antibodies cannot be measured or are negative.

Fatal limbic encephalitis as paraneoplastic neurological syndrome in a patient with lung adenocarcinoma positive for antiamphiphysin antibody after durvalumab treatment.

A 69-year-old Japanese male with advanced lung adenocarcinoma developed neurological symptoms after chemoradiotherapy and durvalumab maintenance therapy. He was positive for serum antiamphiphysin antibody, which is rarely seen in patients with lung adenocarcinoma. Additionally, his brain magnetic resonance images showed limbic encephalitis which led to the diagnosis of classic paraneoplastic neurological syndrome (PNS). Immune checkpoint inhibitors (ICIs) activate T cells and may also activate antineuronal antibodies that cause PNS. Durvalumab, which is an ICI, may have led to antiamphiphysin antibody-positive PNS in our patient. Treatment with systemic high-dose methylprednisolone was unsuccessful and he died 2 months later. PNS should be considered as one of the differential diagnoses in patients with lung cancer and neurological symptoms during, or after, ICI treatment.