Paraneoplastic Autoimmune Encephalitis Research Articles

Comparative Study of Paraneoplastic and Nonparaneoplastic Autoimmune Encephalitis With GABABR Antibodies.

While patients with paraneoplastic autoimmune encephalitis (AE) with gamma-aminobutyric-acid B receptor antibodies (GABABR-AE) have poor functional outcomes and high mortality, the prognosis of nonparaneoplastic cases has not been well studied. Patients with GABABR-AE from the French and the Dutch Paraneoplastic Neurologic Syndromes Reference Centers databases were retrospectively included and their data collected; the neurologic outcomes of paraneoplastic and nonparaneoplastic cases were compared. Immunoglobulin G (IgG) isotyping and human leukocyte antigen (HLA) genotyping were performed in patients with available samples. A total of 111 patients (44/111 [40%] women) were enrolled, including 84 of 111 (76%) paraneoplastic and 18 of 111 (16%) nonparaneoplastic cases (cancer status was undetermined for 9 patients). Patients presented with seizures (88/111 [79%]), cognitive impairment (54/111 [49%]), and/or behavioral disorders (34/111 [31%]), and 54 of 111 (50%) were admitted in intensive care unit (ICU). Nonparaneoplastic patients were significantly younger (median age 54 years [range 19-88] vs 67 years [range 50-85] for paraneoplastic cases, p < 0.001) and showed a different demographic distribution. Nonparaneoplastic patients more often had CSF pleocytosis (17/17 [100%] vs 58/78 [74%], p = 0.02), were almost never associated with KTCD16-abs (1/16 [6%] vs 61/70 [87%], p < 0.001), and were more frequently treated with second-line immunotherapy (11/18 [61%] vs 18/82 [22%], p = 0.003). However, no difference of IgG subclass or HLA association was observed, although sample size was small (10 and 26 patients, respectively). After treatment, neurologic outcome was favorable (mRS ≤2) for 13 of 16 (81%) nonparaneoplastic and 37 of 84 (48%) paraneoplastic cases (p = 0.03), while 3 of 18 (17%) and 42 of 83 (51%) patients had died at last follow-up (p = 0.008), respectively. Neurologic outcome no longer differed after adjustment for confounding factors but seemed to be negatively associated with increased age and ICU admission. A better survival was associated with nonparaneoplastic cases, a younger age, and the use of immunosuppressive drugs. Nonparaneoplastic GABABR-AE involved younger patients without associated KCTD16-abs and carried better neurologic and vital prognoses than paraneoplastic GABABR-AE, which might be due to a more intensive treatment strategy. A better understanding of immunologic mechanisms underlying both forms is needed.

Cerebellar Hypermetabolism in a Hodgkin Lymphoma Leads to Diagnosis of Paucisymptomatic Cryptococcus neoformans Meningitis.

Malignancy-associated cerebellar hypermetabolism on [ 18 F]FDG PET/CT has 2 major causes: paraneoplastic autoimmune encephalitis and neoplasias (leptomeningeal/cerebellar metastases and primary cerebellar tumors). We present the case of a 33-year-old man with a newly diagnosed Hodgkin lymphoma and mere episodical headache, unexpectedly displaying intense cerebellar hypermetabolism on his staging [ 18 F]FDG PET/CT. Both neurolymphomatosis and paraneoplastic subacute cerebellar degeneration were ruled out by clinical presentation, MR, and repeated lumbar punctures. Instead, cerebrospinal fluid analysis unveiled a Cryptococcus neoformans meningitis, highlighting the possibility of paucisymptomatic central nervous system infections as differential diagnosis in malignancy-related cerebellar hypermetabolism in addition to (para)neoplastic causes.

Update on the diagnosis of encephalitis

Autoimmune encephalitis are brain inflammatory processes that are classified into two main groups according to the underlying pathogenic mechanism: antibodies to intracellular antigens (paraneoplastic) and antibodies to extracellular or neuronal surface antigens. The clinical manifestations of autoimmune encephalitis are very varied and non-specific. Complementary tests included in its clinical diagnosis include determination of antibodies in serum or cerebrospinal fluid and magnetic resonance imaging (MRI). MRI may show characteristic patterns such as mesial temporal involvement, although in some cases it may be normal or non-specific. 18F-Fluorodeoxyglucose PET/CT (18F-FDG PET/CT) imaging may be helpful in cases of paraneoplastic autoimmune encephalitis to find the primary tumor. In autoimmune encephalitis mediated by antibodies to extracellular antigens, 18F-FDG PET/CT shows distinctive patterns that can aid clinical diagnosis. This continuing education aims to present in a clear and easy-to-understand way, the clinical features of autoimmune encephalitis, the difficulties in clinical diagnosis and the patterns seen on MRI and 18F-FDG PET/CT.

Actualización en el diagnóstico de la encefalitis

Autoimmune encephalitis are brain inflammatory processes that are classified into two main groups according to the underlying pathogenic mechanism: antibodies to intracellular antigens (paraneoplastic) and antibodies to extracellular or neuronal surface antigens. The clinical manifestations of autoimmune encephalitis are very varied and non-specific. Complementary tests included in its clinical diagnosis include determination of antibodies in serum or cerebrospinal fluid and magnetic resonance imaging (MRI). MRI may show characteristic patterns such as mesial temporal involvement, although in some cases it may be normal or non-specific. 18F-Fluorodeoxyglucose PET/CT (18F-FDG PET/CT) imaging may be helpful in cases of paraneoplastic autoimmune encephalitis to find the primary tumor. In autoimmune encephalitis mediated by antibodies to extracellular antigens, 18F-FDG PET/CT shows distinctive patterns that can aid clinical diagnosis. This special collaboration aims to present in a clear and easy-to-understand way, the clinical features of autoimmune encephalitis, the difficulties in clinical diagnosis and the patterns seen on MRI and 18F-FDG PET/CT.

When Agitation, Hallucination, and Paranoia Mean More Than Psychosis.

When Agitation, Hallucination, and Paranoia Mean More Than Psychosis.

Thymoma-associated autoimmune encephalitis with positive Titin antibodies: A case report

We report a case of thymoma-associated autoimmune encephalitis with positive Titin antibodies. The patient had cognitive dysfunction, psychiatric symptoms and symptomatic epilepsy. PET-CT indicated space-occupied lesion at the thoracic entrance. The patient was diagnosed with paraneoplastic autoimmune encephalitis. After immunotherapy, his condition improved and underwent thymectomy. Pathology revealed type A thymoma. The patient recurred 10 days after the operation. Thymoma is associated with AE. And Titin antibodies may be involved in the extensive immune response to antigens which the patient's thymoma ectopically expressed. This case reflects the complexity of the immune relationship among autoimmune encephalitis, Titin antibodises and thymoma. Titin antibody may have a certain guiding significance for the treatment and prognosis of autoimmune encephalitis.

Infiltration of plasma cells in colorectal adenocarcinoma associated with autoimmune encephalitis

Paraneoplastic autoimmune encephalitis (PAE) represents a group of rare neurological syndromes associated with neoplastic diseases. Here, we report a case that multiple anti‐neuronal antibodies were present in a patient with PAE who developed both small cell lung cancer and colorectal adenocarcinoma. Furthermore, the immunopathological investigation of the colorectal adenocarcinoma revealed the formation of abnormal neuronal antigens and a massive infiltration of plasma cells in the tumor tissue. These findings support the hypothesis that expression of neuronal antigens in neoplasm initiates autoimmune responses in PAE.

1250 Agrypnia Excitata in a Patient with Paraneoplastic Autoimmune Encephalitis

Abstract Introduction Agrypnia Excitata (AE) is a syndrome characterized by loss of sleep with permanent motor and autonomic hyper activation. This case describes this peculiar syndrome in a patient with paraneoplastic autoimmune encephalitis. Report of Case DG is a 35 yr old male with a history of anti-Ma2 limbic encephalitis secondary to cystic teratoma of the left testis diagnosed 6 months prior to presenting in Sleep Clinic. His parents described significant sleep disturbances including short sleep and wake periods throughout the day and night with no apparent pattern, acting out dreams, motor activity during sleep including pulling at his clothes or using his hands to manipulate invisible objects. Additionally they described low-grade fevers, and severe hyperphagia. Polysomnogram showed absence of slow-wave sleep and what appeared to be an admixture of stage 1 non-rapid eye movement (NREM) with rapid-eye movement (REM) sleep. Multiple sleep-latency testing (MSLT) demonstrated a mean sleep latency of 5.2 minutes and four sleep-onset REM periods (SOREMPs). Magnetic resonance imaging of the brain revealed persistent inflammation of the mesial temporal lobes and hippocampal region. Cerebral spinal fluid testing showed persistent anti-Ma2 antibodies. Based on this clinical presentation we made a diagnosis of Agrypnia Excitata. Conclusion Agrypnia Excitata is a syndrome characterized by loss of the normal sleep-wake rhythm. Sleep consists of the disappearance of spindle-delta activities, and persistent stage 1 NREM sleep mixed with recurrent episodes of REM sleep. The second hallmark of AE is persistent motor and autonomic hyperactivity observed during wake and sleep. AE has been described in three distinct clinical syndromes: Morvan Syndrome (autoimmune encephalitis), Fatal Familial Insomnia, and Delirium tremens. The pathogenesis of AE consists of intra-limbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. In autoimmune encephalitis, antibodies that act on voltage-gated potassium channels within the limbic system have been implicated in the pathophysiology.

Seizures due to paraneoplastic anti-n-methyl-d-aspartate reseptor encephalitis associated ovarian teratoma

Background Seizures can be a manifestation of paraneoplastic syndrome which are the consequence of an immune reaction to neuronal elements driven by an underlying malignancy affecting organs and tissues. This immune reaction can cause autoimun encephalitis. One of the antibody commonly that be found in paraneoplastic encephalitis is antibody against neurotransmitter N-Metil D-Aspartat (anti- receptor NMDA). The anti-receptor NMDA paraneoplastic encephalitis is also very rare and the incidence is unclear. In Indonesia this case is rarely found due to the unavailability of NMDA anti-receptor examinations in health care centers resulting in late diagnosis or even undiagnosed. Case report 31-year-old woman with complaints of changes in moody behavior, hallucinations, memory disorders, experienced neurological deterioration in the form of decreased consciousness and seizures (status epilepticus). There is no typical neurological deficit. Normal head MRI examination. EEG examination is obtained ;“extreme delta brush;”. Anti NMDAR examination on CSF has positive results. Gynecological obstetric examination is obtained by a cystic mass with a solid part of the right ovary. The results of anatomical pathology examination on post-salpingooforectomy tissue showed mature cystic teratoma. Follow-up management with anticonvulsant and immunotherapy (steroids, intravenous immunoglobulins, plasmaparesis, immunosuppressants) results in good clinical improvement. Conclusion Consider a paraneoplastic autoimmune encephalitis (anti NMDA receptor encephalitis) as the cause of a neuropsychiatric disorder accompanied by seizures being the main focus in this case. A typical EEG picture can help diagnose. Early diagnosis and adequate management will give a good outcome.

Neuroimaging in status epilepticus secondary to paraneoplastic autoimmune encephalitis

To describe the characteristic magnetic resonance imaging (MRI) findings of paraneoplastic autoimmune encephalitis in patients with new-onset status epilepticus. The neuroimaging and clinical data of five patients with paraneoplastic autoimmune encephalitis debuting as status epilepticus were retrospectively reviewed. All patients met the criteria for definite paraneoplastic syndrome and all underwent brain MRI during the status epilepticus episode or immediately after recovery. All patients showed hyperintense lesions on T2-weighted imaging (WI) involving the limbic structures, specifically the hippocampus. Three of them showed additional extra-limbic areas of signal abnormalities. The areas of T2 hyperintensity were related to the electroclinical onset of the seizures. In three patients, various techniques were used to study cerebral perfusion, such as arterial spin labelling MRI, single photon-emission computed tomography (SPECT) and 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG)-positron-emission tomography (PET). Arterial spin labelling showed hyperperfusion overlapping the inflammatory lesions, whereas PET and SPECT disclosed increased perfusion and increased metabolism. The subtraction SPECT co-registered to MRI (SISCOM) demonstrated hypermetabolism outside the areas of encephalitis. After clinical recovery, follow-up MRI revealed the development of atrophy in the initially affected hippocampus. Two patients who had recurrent paraneoplastic autoimmune encephalitis manifesting as status epilepticus showed new T2 lesions involving different structures. The presence of limbic and extra-limbic T2 signal abnormalities in new-onset status epilepticus should suggest the diagnosis of a paraneoplastic syndrome, especially when status epilepticus is refractory to treatment. The lesions are consistently seen as hyperintense on T2WI.

Autoimmune-Mediated Cognitive Impairment: A Case Report

Autoimmune encephalopathy encompasses a complex groupof diseaseswith diverse clinicalmanifestations and therapeutic outcomes. Central nervous system (CNS) autoimmune inflammation can be triggered in multiple ways, including (1) systemic infections/vaccinations, (2) various cancers (paraneoplastic autoimmune encephalitis), (3) systemic autoimmunedisorders, and (4)without an identifiable cause (e.g., nonparaneoplastic autoimmune encephalitis). The discovery of neuropsychiatric disorders associated with antibodies to neuronal cell surface proteins, which play a crucial role in synaptic transmission and plasticity, has resulted in a paradigm shift in our understanding of CNS autoimmunity. We report a case of a young woman with multiple autoimmune disorders who presented with significant memory problems and relapse of major depressive disorder. Her cognitive problems did not resolve upon treatment of depression and continued to result in significant impairment of her daily functioning. A comprehensive neuropsychiatric and neurologic evaluation helped in establishing and providing a successful treatment. This case underscores the importance of recognizing neuropsychiatric manifestations of autoimmune disorders and the use of a multidisciplinary approach for the evaluation and treatment of neuropsychiatric conditions. Medicine, Baltimore, MD; Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, OH. Send correspondence and reprint requests to Bhargavi Devineni,M.B.B.S., Division of Geriatrics and Neuropsychiatry, Department of Psychiatry, Johns Hopkins University of Medicine, 5300 Alpha Commons Drive 4th Floor, Alpha Commons Building, Baltimore, MD 21224; e-mail: bdevine2@jhmi.edu & 2014TheAcademy of PsychosomaticMedicine. Published by Elsevier Inc. All rights reserved. Case Report

Paraneoplastic autoimmune encephalitis associated with CV2/CRMP-5 IgG antineuronal antibodies in a patient with thymoma

Paraneoplastic autoimmune encephalitis associated with CV2/CRMP-5 IgG antineuronal antibodies in a patient with thymoma