Four kinds of antibody positive paraneoplastic limbic encephalitis: A rare case report

BACKGROUND It is not uncommon to develop autoimmune encephalitis and paraneoplastic neurological syndromes(PNS).4 kinds of antibody-positive autoimmune paraneoplastic limbic encephalitis(PLE)have not been reported.CASE SUMMARY PNS are distant effects of cancer on the nervous system,rather than syndromes in which cancer directly invades and metastasizes to the nerves and/or muscle tissues.If the limbic lobe system of the brain is involved,this will result in PLE.The detection of patients with PNS is challenging since tumors that cause paraneoplastic neurologic disorders are often asymptomatic,obscure,and thus easily misdiagnosed or missed.Currently,single-or double-antibody-positive paraneoplastic marginal encephalitis has been reported.However,no cases of three or more-antibody-positive cases have been reported.Here,we report a case of PLE that is anti-collapsing response-mediator protein-5,anti-neuronal nuclear antibody-type 1,anti-aminobutyric acid B receptor,and anti-glutamate deglutase positive,and address relevant literature to improve our understanding of the disease.CONCLUSION This article reports on the management of a case of PLE with four positive antibodies,a review of the literature,in order to raise awareness among clinicians.

White matter connectivity damage secondary to hippocampal and amygdala target injuries in acute limbic encephalitis Diffusion tensor image and voxel-based morphometry paired study

BACKGROUND： Limbic encephalitis is a rare syndrome that specifically affects the limbic system. Magnetic resonance imaging （MRI） has been typically used to detect brain changes in this disease. However, the mechanisms of limbic encephalitis-related white matter damage remain poorly understood. OBJECTIVE： To characterize white matter connectivity changes secondary to injuries of the limbic system in limbic encephalitis through combined application of diffusion tensor imaging （DTI） and voxel-based morphometry. DESIGN, TIME AND SETTING： A non-randomized, controlled, clinical, neuroimaging, DTI study was performed at the Department of Radiology, West China Hospital in December 2008. PARTICIPANTS： A male, 46-year-old, limbic encephalitis patient, as well as 11 age- and gender-matched healthy volunteers, were enrolled in the present study. METHODS： MRI was performed on the limbic encephalitis patient using a 3.0T MR scanner. Three-dimensional SPGR Tl-weighted images and DTI were acquired in the patient and controls. Data were analyzed using Matlab 7.0 and SPM2 software. MAIN OUTCOME MEASURES： Results from routine MRI scan with contrast enhancement of patient, as well as fractional anisotropy and mean diffusivity value map differences between patient and controls. RESULTS： Significant symmetric MRI signal intensity abnormalities were observed with routine MRI Affected bilateral hippocampi and amygdala exhibited hypointense signals in TIWI and hyperintense signals in T2 images. The DTI study revealed decreased fractional anisotropy values in the bilateral alveus and fimbria of the hippocampus, bilateral internal and external capsules, white matter of the right prefrontal area, and left corona radiate in the patient compared with normal controls （P 〈 0.001） Significantly increased fractional anisotropy, mean diffusivity, or decreased mean diffusivity were not observed in the patient, compared with controls. CONCLUSION： Secondary white matter damage to the hippocampal afveus and fimbria was apparent in the limbic encephalitis patient. In addition, other white matter fiber injuries surrounded the limbic structures, which were not attributed to secondary limbic system injuries.

Limbic Encephalitis as the First Manifestation of Neurosyphilis: A Diagnostic Challenge

Limbic encephalitis (LE) is a clinical entity related to a mesial temporal lesion resulting in a combination of anterograde memory dysfunction, behavioral changes, and seizures. The most common causes of limbic encephalitis are Herpes Simplex Virus (HSV) encephalitis, autoimmune encephalitis. Neurosyphilis is an exceptional aetiology. The early diagnosis and management of the disease determine the prognosis. This clinical course highlights the diagnostic challenge limbic encephalitis can cause and the importance of considering neurosyphilis in patients with specific or unspecific neurological symptoms. We report a case of a mesiotemporal form of neurosyphilis revealed by a LE.

Limbic Encephalitis Associated with Anti-y-aminobutyric Acid B Receptor Antibodies： A Case Series from China

Background： Autoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor （GABABR） in patients with limbic encephalitis （LE） was first described in 2010. We present a series of klan Chinese patients tbr further clinical refinement. Methods： Serum and cerebrospinal fluid （CSF） samples from patients referred to the program of encephalitis and paraneoplastic syndrome of Peking Union Medical College Hospital were tested with indirect immunofluorescence. Clinical information of patients with anti-GABABR antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed. Results： All eighteen anti-GABABR antibody-positive cases had limbic syndromes, and electroencephalogram （EEG） or neuroimaging evidence fulfilled the diagnostic criteria of LE. Four patients had additional antibodies against Hu in serum and one had anti-N-methyl-d-aspartate receptor antibody in both sera and CSF. Seventeen （17/18） patients presented with new-onset refractory seizure or status epileptics. Twelve （12/18） patients had memory deficits, 11 （11/18） patients had personality change, 7 （7/18） patients had disturbance of consciousness, and 3 （3/18） patients showed cerebellar dysfunction. One patient with LE had progressive motor and sensory polyneuropathy. Lung cancer was detected in 6 （6/18） patients. Ten （10/18） patients showed abnormality in bilateral or unilateral mediotemporal region on magnetic resonance imaging. Ten （10/18） patients had temporal lobe epileptic activity with or without general slowing on EEG. Seventeen patients received immunotherapy and 15 of them showed neurological improvement. Four patients with lung cancer died within 1-12 months due to neoplastic complications. Conclusions： Our study demonstrates that most Han Chinese patients with anti-GABABR antibody-associated LE have prominent refractory epilepsy and show neurological improvement on immunotherapy. Patients with underlying lung tumor have a relatively poor prognosis. Testing for anti-GABABR antibodies is necessary for patients with possible LE or new-onset epilepsy with unknown etiology.

A Rare Case of Ovarian Cancer Presenting with Paraneoplastic Cerebellar Degeneration and Limbic Encephalitis

Paraneoplastic neurologic syndromes （PNSs） occur with increased frequency in patients with cancer and almost always antedate its diagnosis.These syndromes comprise a heterogeneous group of cancer-related neurologic diseases,and they may affect any part of the nervous system.The simultaneous involvement of different areas of the nervous system by the paraneoplastic process is not unusual.Until date,this is the first report of concurrent development of paraneoplastic cerebellar degeneration （PCD） and paraneoplastic limbic encephalitis （PLE） associated with the advanced ovarian cancer and anti-Yo antibodies following hepatitis B （HB） vaccination.The cause of most PNS is believed to be an immune response against neuronal proteins expressed by the tumor.

Gamma-aminobutyric-acid-B receptor antibodies in limbic encephalitis with small cell lung cancer

Encephalitis associated with antibodies to gamma-aminobutyric-acid B(GABA-B)is a subgroup of autoimmune synaptic encephalitis with typical features of limbic encephalitis and small cell lung cancer(SCLC).We report a case of anti-GABA-B receptor encephalitis in a 57-year-old man who presented with seizures,memory loss,and abnormal behavior.He developed partially neurological responses to immunotherapy,but refused comprehensive tumor screening.The symptoms were aggravated again 4 months later.Workup showed antibodies to GABA-B receptors and tumor screening revealed SCLC.It highlights the importance of early screening of underlying tumor and anti-tumor treatment in paraneoplastic cases.

Neurological complications of hematopoietic cell transplantation in children and adults

Hematopoietic cell transplantation（HCT） is widely performed for neoplastic and non-neoplastic diseases. HCT involves intravenous infusion of hematopoietic progenitor cells from human leukocyte antigen（HLA）-matched donor（allogeneic） or from the patient（autologous）. Before HCT, the patient is prepared with high dose chemotherapy and/or radiotherapy to destroy residual malignant cells and to reduce immunologic resistance. After HCT, chemotherapy is used to prevent graft rejection and graft versus host disease（Gv HD）. Neurological complications are related to the type of HCT, underlying disease, toxicity of the conditioning regimens, immunosuppression caused by conditioning regimens, vascular complications generated by thrombocytopenia and/or coagulopathy, Gv HD and inappropriate immune response. In this review, neurological complications are presented according to time of onset after HCT：（1） early complications（in the first month）-related to harvesting of stem cells, during conditioning（drug toxicity, posterior reversible encephalopathy syndrome）, related to pancytopenia,（2） intermediate phase complications（second to sixth month）-central nervous system infections caused by prolonged neutropenia and progressive multifocal leukoencephalopathy due to JC virus,（3） late phase complications（after sixth month）-neurological complications of Gv HD, second neoplasms and relapses of the original disease.

Encephalitis associated with autoantibodies binding toγ-aminobutyric acid-A,γ-aminobutyric acid-B and glycine receptors:immunopathogenic mechanisms and clinical characteristics

Recent,discoveries of neural antibodies have facilitated the diagnosis of immune-mediated,immunotherapy-responsive neurologic disorders.Antibodies that target inhibitory central nervous system receptors,such asγ-aminobutyric acid-B,γ-aminobutyric acid-A,and glycine receptors,disrupt inhibitory regulatory synaptic functions,and lead to neuronal hyperexcitability.The myriad of neurologic,manifestations associated with these antibodies includes seizures,encephalopathy,muscle rigidity and stiffness.This article provides a review of the immunopathogenic mechanisms and the clinical and therapeutic implications of autoimmune encephalitis associated with these antibodies that target inhibitory receptors.

Neurological diseases associated with autoantibodies targeting the voltage-gated potassium channel complex:immunobiology and clinical characteristics

Voltage-gated potassium channels(VGKCs)represent a group of tetrameric signaling proteins with several functions,including modulation of neuronal excitability and neurotransmitter release.Moreover,VGKCs give a key contribution to the generation of the action potential.VGKCs are complexed with other neuronal proteins,and it is now widely known that serum autoantibodies directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients.By contrast,these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts.These three proteins are contactin-associated protein-2(Caspr-2),leucine-rich,glioma inactivated 1(LGI-1)protein and the protein Tag-1/contactin-2.Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG and do not significantly associate with Caspr-2 or LGI-1.Among all the cancers described in association with VGKC complex-IgG,lung carcinoma,thymoma,and hematologic malignancies are the most commonly detected.We will review all the major neurological conditions associated with VGKC complex-IgG.These include Isaacs’syndrome,Morvan syndrome,limbic encephalitis,facio-brachial dystonic seizures,chorea and other movement disorders,epilepsy,psychosis,gastrointestinal neuromuscular diseases,a subacute encephalopathy that mimics Creutzfeldt-Jakob prion disease both clinically and radiologically and autoimmune chronic pain.The vast majority of these conditions are reversible by immunotherapy,and it is becoming increasingly recognized that early diagnosis and detection of VGKC complex-IgG is critical in order to rapidly start the treatment.As a result,VGKC complex-IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy,memory or cognitive problems,or peripheral nerve hyperexcitability syndromes.