Autoimmune Meningoencephalitis Research Articles

A case of reversible isolated cognition impairment in meningoencephalitis without abnormal MRI findings

AbstractBackgroundWe report a case of meningoencephalitis with reversible isolated cognition impairment without abnormal MRI findings.MethodA 75‐year‐old man presented with confusion including bizarre behavior 2 days ago. Before visiting the hospital, his son found the patient naked and under the blanket saying it was cold. Fever didn’t occur. Mental status was alert without awareness. On neurologic examination, mutism was found. Muscle power on both upper and lower limbs was normal. Routine laboratory test showed that leukocytes count was normal but eosinophils were increased to 14.0%. Initial brain MRI including DWI and contrast enhanced image revealed no enhanced structural lesions. Initial K‐MMSE score was 4 points while the previous K‐MMSE score 3‐months‐ago was 25 points. There was no epileptic form discharge in EEG. CSF study demonstrated that WBC count was 18/L. protein was 42.6mg/dL, and glucose was 103mg/dL. CSF opening pressure was 5cmH2O. Culture study including gram stain, AFB stain, PAS stain showed no growth of aerobe, anaerobe, fungus and hyphae. Mycobacterium tuberculosis PCR and HSV PCR were negative. ADA was under 3 IU/I. Serum paraneoplastic antibodies were all negative.ResultThe patient showed only isolated cognition impairment without fever and there was no evidence of meningoencephalitis on the contrast enhanced MRI. Although the patient revealed CNS infection with unknown cause in CSF profile, it has some possibilities; 1) Aseptic meningoencephalitis with viral infection, 2) Bacterial meningoencephalitis with early stage, 3) Parasitic meningoencephalitis, 4) Autoimmune meningoencephalitis. Because of the negative findings in autoimmune antibody test, autoimmune meningoencephalitis was less likely. After treatment with acyclovir 0.6g for 7days, ceftriaxone 4g, vancomycin 2.5g and Ampicillin 8g for 10 days, confusion and mutism were improved with K‐MMSE 18 points.ConclusionMany reports have been published on meningoencephalitis accompanied by fever, altered mentality, seizure, muscle weakness and abnormal MRI findings respectively. However there have been few cases of meningoencephalitis with isolated cognition impairment and normal MRI simultaneously. If it is a change of consciousness and cognition impairment caused by meningoencephalitis, it can be reversible with proper treatment. Therefore, if only sudden onset isolated CNS symptom with normal brain MR finding, it is essential to check CSF profile.

Dural and Leptomeningeal Diseases: Anatomy, Causes, and Neuroimaging Findings.

Meningeal lesions can be caused by various conditions and pose diagnostic challenges. The authors review the anatomy of the meninges in the brain and spinal cord to provide a better understanding of the localization and extension of these diseases and summarize the clinical and imaging features of various conditions that cause dural and/or leptomeningeal enhancing lesions. These conditions include infectious meningitis (bacterial, tuberculous, viral, and fungal), autoimmune diseases (vasculitis, connective tissue diseases, autoimmune meningoencephalitis, Vogt-Koyanagi-Harada disease, neuro-Behçet syndrome, Susac syndrome, and sarcoidosis), primary and secondary tumors (meningioma, diffuse leptomeningeal glioneuronal tumor, melanocytic tumors, and lymphoma), tumorlike diseases (histiocytosis and immunoglobulin G4-related diseases), medication-induced diseases (immune-related adverse effects and posterior reversible encephalopathy syndrome), and other conditions (spontaneous intracranial hypotension, amyloidosis, and moyamoya disease). Although meningeal lesions may manifest with nonspecific imaging findings, correct diagnosis is important because the treatment strategy varies among these diseases. ©RSNA, 2023 Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article. Quiz questions for this article are available through the Online Learning Center.

Autoimunitní meningoencefalitida asociovaná s anti­‑GFAP protilátkami - kazuistika

Autoimunitní meningoencefalitida asociovaná s anti­‑GFAP protilátkami - kazuistika

An Atypical Case of GFAP Astrocytopathy

Objective To describe a case of anti-GFAP astrocytopathy with atypical features. Background Glial fibrillary acidic protein (GFAP) astrocytopathy is a steroid-responsive autoimmune meningoencephalitis that is commonly characterized by preceding viral illness followed by encephalopathy and papillitis without significant effect on visual acuity. We describe an atypical case of GFAP astrocytopathy presenting with profound vision loss and intracranial hypertension. Design/Methods Case Report Results 31 yo male with a history of hypertension developed flu-like symptoms for one week. Subsequently, he experienced blurry vision and presented to the hospital. He was found to be hypertensive with acute kidney injury. He was treated for hypertensive urgency and discharged. However, patient's vision continued to deteriorate and he developed non-threatening visual hallucinations. He was readmitted to the hospital. His eye exam revealed bilateral loss of visual acuity, retinal hemorrhages and severe papilledema. His laboratory work-up was notable for LP findings of lymphocytic pleocytosis, elevated protein and opening pressure of 54. He was started on acetazolamide and transferred to tertiary medical center. There, he developed encephalopathy with psychosis. An extensive infectious/ autoimmune/malignancy workup was completed. This included three repeat LPs showing persistent intracranial hypertension, lymphocytic pleocytosis, high protein and oligoclonal bands. He underwent imaging with CT chest/abdomen/pelvis, MRV and MRI head/orbits, which showed no evidence of malignancy, patent vasculature and pachymeningeal enhancement, respectively. His work-up was notable for positive IgG GFAP in CSF leading to diagnosis of GFAP astrocytopathy. He was treated with pulse dose IV steroids followed by slow steroid taper and concurrent PLEX therapy. Due to severity of case, he was later started on cyclophosphamide. For papilledema, he was continued on acetazolamide and underwent bilateral optic nerve sheath fenestration. Overall, his encephalopathy resolved but vision remained poor. Conclusions This case illustrates an unique manifestation of GFAP astrocytopathy including rapid visual loss, persistent intracranial hypertension and absence of characteristic MRI findings.

Autoimmune meningoencephalitis associated with anti‐glutamic acid decarboxylase antibody following COVID‐19 infection: A case report

Anti-glutamic acid decarboxylase (Anti-GAD) are associated with various neurologic condition; but no meningitis has been reported with it, so far. Evidence demonstrates the associated of autoimmune meningoencephalitis with COVID-19 infection. Here, we report a 44-year-old female with progressive loss of consciousness with anti-GAD65 meningoencephalitis 1 month after COVID-19 infection.

Diagnosis and treatment of autoimmune diseases of the brain and spinal cord in dogs: analysis of the literature review

The main methods of diagnosing these diseases, according to the analysis of world literature data, are the analysis of the patient's cerebrospinal fluid and magnetic resonance imaging (MRI). The analysis of cerebrospinal fluid (CSF) is carried out in order to detect changes characteristic of the diagnosis. With the help of MRI, it is possible to determine the localization of inflammation. A number of studies have been aimed at improving diagnostic methods by detecting new factors characteristic of autoimmune diseases of the nervous system. Data on the detection of antibodies corresponding to human antibodies in the cerebrospinal fluid of dogs and on changes in the concentration of various substances in it are presented. This allows for faster and more accurate diagnostics.As a result of the generalization of the literature data, it was found that immunosuppressive drugs are used for the treatment of autoimmune diseases of the brain and spinal cord of dogs. According to the data presented, the most effective of the known methods of treatment of autoimmune meningoencephalitis is the use of a combination of prednisolone and imatinib mesylate. For the treatment of steroid-dependent meningoarteritis (SRMA), various corticosteroid drugs are used, the most optimal of which is the combination of prednisone and cytarabine.The purpose of our study was to study modern Russian and foreign literature sources on autoimmune diseases of the brain and spinal cord in dogs, methods of diagnosis and treatment of these diseases and to review works that provide new data on their treatment, diagnosis and understanding of etiology and pathogenesis.

Perplexing Infectious Etiology of a Case of Hypopituitarism and Central Diabetes Insipidus

Injury to the hypothalamus and both the anterior and posterior components of the pituitary gland is rare, but can result from infiltrative processes such as sarcoidosis, Langerhans cell histiocytosis, granulomatous with polyangiitis, and lymphocytic hypophysitis. Meningitis, pituitary infection, traumatic brain injury, and surgical instrumentation are other etiologies.A 40 year old man with mild cognitive impairment due to remote meningitis was evaluated for progressive somnolence. He was obtunded and cerebrospinal fluid (CSF) analysis revealed 11 WBC with lymphocytic pleocytosis (90% lymphocytes), highly elevated protein of 588 mg/dL (ref range 12-60 mg/dL), and low glucose of 17 mg/dL (ref range 40-70 mg/dL). MRI Brain revealed basilar meningitis/rhombencephalitis and suspected infectious vasculitis induced right middle cerebral artery territory stroke. Of note, there was substantial T2 hyperintense signaling in the hypothalamus and pituitary areas, which has been reported with tuberculosis (TB), Coccidioidomycosis (Cocci), and the aforementioned etiologies. He received broad antimicrobials, including TB treatment and fluconazole. He developed sinus bradycardia, hypotension, hypoglycemia, and hypothermia. Labs demonstrated inappropriately normal TSH of 1.4 mclU/mL (ref range 0.35-4.94 mclU/mL), low free T4 (fT4) of 0.50 ng/dL (ref range 0.7-1.48 ng/dL) with repeat fT4 undetectably low the following day, and AM cortisol less than 0.5mcg/dL (ref range 4-22 mcg/dL). Levothyroxine and steroids were initiated. He then developed central diabetes insipidus (DI) for which DDAVP was initiated. Comprehensive infectious and autoimmune meningoencephalitis workup was unrevealing. Serum and CSF tests for Listeria PCR, Cocci antibody and antigen, and TB were negative upon multiple, serial checks spanning weeks. CSF analysis one month later showed improvement in protein level (106 mg/dL), but still with elevated WBC (10 WBCs, 98% lymphocytes). MRI one month later demonstrated improvement in edema and the areas of ischemia and vasculitis were less. His adrenal insufficiency and central DI were transient and improved, no longer requiring steroids or DDAVP. He remains on levothyroxine for central hypothyroidism.The MRI and CSF findings point to an infectious etiology for hypopituitarism and central DI. We suspect an indolent bacteria such as Listeria or a fungus, likely Cocci, or TB meningitis. Cocci seemed to provide a unifying explanation as it classically creates infarcts and causes vasculitis. However, serial CSF tests were negative for Cocci, as well as for TB and Listeria. Marked improvement on follow up MRI also makes TB meningitis less likely as imaging would not resolve so quickly. This is a mysterious case; he improved on broad antimicrobial therapy and is being monitored closely in the outpatient setting.

Glial Fibrillary Acidic Protein Astrocytopathy in Pediatric Patients: A Retrospective Study.

Autoimmune glial fibrillary acidic protein astrocytopathy is a novel form of autoimmune meningoencephalitis related to GFAP autoantibodies. This condition is still being characterized, and few pediatric patients have been identified. Here, we report three patients presenting with fever, nausea, and headache, following progressive disturbance of consciousness, limb weakness, dyspnea, or urine retention. MRI analysis revealed that T2-hyperintense lesions, or enhancement of the meninges and spinal cord. CSF and serum analyses revealed they were positive for GFAP antibody, confirming GFAP astrocytopathy diagnosis. Treating the patients with IVIG, with or without intravenous steroids, gradually improved their clinical symptoms. Our findings indicate that GFAP astrocytopathy should be considered in children who are clinically diagnosed with meningoencephalitis, whether or not myelitis is present, and if the MRI reveals enhancement of meninges or spinal cord, T2-hyperintense lesions, or a pattern of linear perivascular gadolinium enhancement. Suspected cases should be tested for GFAP antibody as soon as possible because these patients may benefit from immunotherapy.

Plasmapheresis treatment in COVID-19–related autoimmune meningoencephalitis: Case series

Severe SARS-CoV-2 (COVID-19) infection has the potential for a high mortality rate. In this paper, we report the results of plasmapheresis treatment in a series of severely ill patients with COVID-19–related autoimmune meningoencephalitis in the Intensive Care Unit (ICU).

Glial fibrillary acidic protein (GFAP) associated autoimmune meningoencephalitis in a patient receiving nivolumab

Immune checkpoint inhibitors (ICIs) represent a major development in cancer treatment, allowing for improved survival and disease control in an expanding number of cancer types. Due to their mechanism of disrupting immunologic homeostasis, ICIs are frequently associated with adverse effects, termed immune related adverse effects (irAE). These side effects can affect any organ system, including the central and peripheral nervous systems.We present a case of a 47 year old man with stage IIIc metastatic melanoma who received 3 cycles of nivolumab (a monoclonal antibody inhibitor of programmed cell death protein 1 (PD-1)). After completing the third cycle, he presented with a meningoencephalitis clinical picture with an inflammatory cerebrospinal fluid (CSF) and normal MRI. He was found to have a positive anti-glial fibrillary acidic protein (GFAP) autoantibody in his CSF by immunofluorescent assay (IFA) and cell based assay (CBA) which confirmed a diagnosis of anti-GFAP autoimmune encephalitis. He was treated with immunotherapy and made a full recovery. In this report, we present the first reported case of anti-GFAP autoimmune encephalitis associated with ICI therapy and provide a brief review of the literature.

CHRONIC EOSINOPHILIC PNEUMONIA IN A PATIENT WITH AUTOIMMUNE MENINGOENCEPHALITIS

SESSION TITLE: Diffuse Lung Diseases SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/22/2019 3:45 PM - 4:45 PM INTRODUCTION: Glial fibrillary acidic protein (GFAP) encephalomyelitis is a newly described form of autoimmune meningoencephalitis that is characterized by GFAP-specific antibodies.1 This condition has been associated with a high incidence of malignancy, but to date there are no known associated pulmonary diseases. CASE PRESENTATION: A 58-year-old man with a history of GFAP encephalomyelitis was referred for evaluation of symmetric, upper-lobe predominant ground-glass infiltrates (Figure 1). He reported only minimal cough. For GFAP he was being treated with mycophenolate mofetil, prednisone, and appropriate prophylactics. He was completing a prednisone taper at his initial presentation. He underwent bronchoscopy with bronchoalveolar lavage (BAL). Cytology and infectious studies were negative. There were 44 total nucleated cells (TNC), 20% of which were eosinophils. Pulmonary function tests (PFTs) showed no obstruction or restriction, but the DLCO was reduced at 59% predicted. He had normal autoimmune markers, serum protein electrophoresis, and free light chains. He returned for a 3-month follow-up with worsening cough and dyspnea. He had new restriction on PFTs (TLC 64% predicted, FVC 58% predicted). A repeat chest CT showed significant progression of his prior infiltrates (Figure 2) and mild lymphadenopathy. In the interim, he had discontinued prednisone, but remained on pneumocystis prophylaxis. A urinalysis, creatine kinase, aldolase, and hypersensitivity pneumonitis panel were within normal limits. He underwent bronchoscopy with BAL and transbronchial biopsies. Cytology and infectious studies were negative. There were 42 TNC, 34% of which were eosinophils. Pathology showed organizing pneumonia with eosinophils. He was treated with 60mg of prednisone with a planned taper and prescribed oxygen. He noted significant improvement after re-starting steroids and at 3-month follow-up, he was taking 20mg of prednisone and had no pulmonary limitations. A chest CT showed significant improvement (Figure 3) and PFTs demonstrated improvement (TLC to 85% predicted, FVC 91% predicted). DISCUSSION: The patient's elevated eosinophil count in his BAL, evidence of eosinophils with concurrent organizing pneumonia on transbronchial biopsies, and rapid response to steroids is most consistent with chronic eosinophilic pneumonia. Although his neurologic disease did not have a concurrent exacerbation with his lung disease, the co-occurrence of these two rare conditions suggests a potential association between them. CONCLUSIONS: This represents the first reported case of chronic eosinophilic pneumonia associated with GFAP meningoencephalomyelitis. Further study into an association between these two entities is warranted Reference #1: Fang B, McKeon A, Hinson SR, et al. Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Novel Meningoencephalomyelitis. JAMA neurology. 2016;73(11):1297-1307. DISCLOSURES: No relevant relationships by Cassandra Braun, source=Web Response No relevant relationships by Gregory Stroh, source=Web Response

Three Japanese adult cases of brain lesions with anti‐myelin oligodendrocyte glycoprotein antibodies lacking optic neuritis and myelitis

AbstractBackgroundAnti‐myelin oligodendrocyte glycoprotein antibodies (MOG‐Ab) are positive in some patients with neuromyelitis optica/neuromyelitis optica spectrum disorders; however, their clinical diversity remains unclear.Case presentationWe encountered three anti‐MOG‐Ab‐positive Japanese adult patients with brain lesions, but lacking optic neuritis and myelitis. Magnetic resonance imaging detected lesions in the cerebral gray and white matter, brainstem, and cerebellum, and 18‐fluorodeoxyglucose positron emission tomography imaging showed normal or decreased uptake in acute lesions.ConclusionsPatients with anti‐MOG‐Ab might present with brain lesions only, and lack optic neuritis and myelitis. The anti‐MOG‐Ab titer needs to be measured in inflammatory diseases that affect the central nervous system, including atypical multiple sclerosis and autoimmune meningoencephalitis.

Lesions of the posterior limb of the internal capsule in neuromyelitis optica spectrum disorder

Posterior limb of the internal capsule lesions (PLICL) are one of the MRI features of neuromyelitis optica spectrum disorder (NMOSD). However, there is no evidence that such lesions are pathogenically related to NMOSD. We retrospectively analyzed features of PLICL in NMOSD, and other central nervous system inflammatory disorders, in 561 patients. We also examined the pathological samples of six patients. Of the 561 patients investigated, PLICL were found in 65 patients (11.6%). Lesions were bilateral in 26 cases (40%) and unilateral in 39 cases (60%). Unilateral lesions were mainly located on the left side (74.3%, 29/39). Of the 65 patients with PLICL, 46 patients had NMOSD (70.8%) and were positive for anti-aquaporin (AQP4-IgG), four had NMOSD (6.2%) and were AQP4-IgG negative, 10 patients had multiple sclerosis (MS), three patients had NMDAR encephalitis, and two had autoimmune meningoencephalitis. Of the six patients whose pathological samples were evaluated, all had PLICL and were negative for AQP4-IgG, and none had pathological NMOSD lesion features. These cases included three patients with multiple sclerosis, one with anti-N-methyl-D-aspartate receptor encephalitis, and two with autoimmune meningoencephalitis. In conclusion, PLICL are found not only in patients with NMOSD, but also in MS and other disorders.

Nonvasculitic Autoimmune Meningoencephalitis After Rituximab

Nonvasculitic autoimmune meningoencephalitis (NAIM) is a rare condition describing a syndrome of steroid-responsive encephalopathy in patients with similar clinical and pathologic features. It can be associated with autoimmune diseases, such as Sjogren's syndrome and autoimmune thyroiditis. Brain biopsies usually show inflammatory cells without evidence of vasculitis. In this article, we present a patient who developed NAIM after receiving rituximab, a B-cell-depleting therapy for rheumatoid arthritis. The brain biopsy showed a lack of B lymphocytes in the brain tissue, and the patient responded well to intravenous immunoglobulins. We further discuss the role of B lymphocytes and specific regulatory B lymphocytes in suppressing autoimmunity in the brain and propose that the depletion of regulatory B cells may contribute to the pathogenesis of NAIM. This case illustrates a potential side effect of rituximab and demonstrates the importance of regulatory B cells in maintaining the immune response.

A comprehensive strategy for dementia from primary prevention to end‐stage management

A comprehensive strategy for dementia from primary prevention to end‐stage management

Modified Immunotherapies Against Alzheimer's Disease: Toward Safer and Effective Amyloid-β Clearance

Alzheimer's disease (AD) is characterized by the deposition of amyloid plaques, loss of neurons, neuritic degeneration, accumulation of fibrillary tangles in neurons, and a progressive loss of cognitive function. Amyloid-β peptide (Aβ) appears to play a pivotal role in the development of AD. Clearance of Aβ from the brain represents an important therapeutic strategy for prevention and treatment of AD. Immunotherapy targeting Aβ is effective to remove the peptide from the brain. However, it is associated with detrimental adverse effects, such as autoimmune meningoencephalitis and microhemorrhage. These are presumably the results of brain infiltration of provoked autoimmune T lymphocytes in response to Aβ vaccination and release of proinflammatory cytokines from microglia activated by the immune complex of Aβ and antibodies. An improvement of the safety of the immunotherapy is a major goal of the immunotherapy study. Here, we review the mechanisms involved in modified immunological strategies, as well as their adverse effects. We discuss the following: the development of B epitope vaccines to avoid activation of autoimmune T lymphocytes; DNA vaccines containing appropriate immunostimulatory and immunomodulatory sequences to induce the desired humoral immune responses; antibody modifications to avoid activation of microglia and subsequent release of proinflammatory cytokines; single chain antibodybased gene therapy; immunotherapy targeting Aβ oligomers; modulation of antibody delivery approach and dose; and application of autoantibodies against Aβ. These ultimately represent future directions of therapeutic approaches toward safer and effective Aβ clearance.

Encefalopatía subaguda con respuesta a esteroides sin evidencia de enfermedad autoinmune tiroidea: un caso de meningoencefalitis autoinmune no vasculítica

To report a case of sub-acute encephalopathy with all the extension study negative and with response to steroid therapy.The study involves a 22-year-old female with no relevant past history who presented symptoms of sub-acute encephalopathy consisting in behavioural disorders, generalised seizures and bradypsychia, which gradually progressed to a state of low-level consciousness. While she was in hospital all kinds of diagnostic tests were conducted, the results of which were either normal or negative; the electroencephalogram was repeatedly abnormal and detection of protein 14-3-3 in cerebrospinal fluid was positive. Empirical corticoid therapy was begun with clinical and electrophysiological improvements and the patient recovered completely without any sequelae.With no evidence of autoimmune thyroid disease, although non-specific autoimmunity was present, the patient was diagnosed as having non-vasculitic autoimmune meningoencephalitis.

Antibodies to Potato Virus Y Bind the Amyloid β Peptide: IMMUNOHISTOCHEMICAL AND NMR STUDIES

Studies in transgenic mice bearing mutated human Alzheimer disease (AD) genes show that active vaccination with the amyloid beta (Abeta) protein or passive immunization with anti-Abeta antibodies has beneficial effects on the development of disease. Although a trial of Abeta vaccination in humans was halted because of autoimmune meningoencephalitis, favorable effects on Abeta deposition in the brain and on behavior were seen. Conflicting results have been observed concerning the relationship of circulating anti-Abeta antibodies and AD. Although these autoantibodies are thought to arise from exposure to Abeta, it is also possible that homologous proteins may induce antibody synthesis. We propose that the long-standing presence of anti-Abeta antibodies or antibodies to immunogens homologous to the Abeta protein may produce protective effects. The amino acid sequence of the potato virus Y (PVY) nuclear inclusion b protein is highly homologous to the immunogenic N-terminal region of Abeta. PVY infects potatoes and related crops worldwide. Here, we show through immunocytochemistry, enzyme-linked immunosorbent assay, and NMR studies that mice inoculated with PVY develop antibodies that bind to Abeta in both neuritic plaques and neurofibrillary tangles, whereas antibodies to material from uninfected potato leaf show only modest levels of background immunoreactivity. NMR data show that the anti-PVY antibody binds to Abeta within the Phe4-Ser8 and His13-Leu17 regions. Immune responses generated from dietary exposure to proteins homologous to Abeta may induce antibodies that could influence the normal physiological processing of the protein and the development or progression of AD.

Treatment and Management of the Elderly Patients with Alzheimer's Disease

Alzheimer's disease (AD) is the most common cause of dementia in older people. Cerebral deposition of amyloid plaques containing amyloid beta-peptide (Aβ) has traditionally been considered the central feature of AD. γ-Secretase is the pivotal enzyme in generating the C terminus of Aβ, that determines its aggregability and propensity for deposition. Drugs that regulate the production of Aβ by inhibiting gamma-secretase activity could provide an effective therapeutics for AD, however we can't use these drugs clinically now. Anti-amyloid immunotherapy for AD has received considerable attention following reports that amyloid pathology was reduced in an amyloid precursor protein (APP) transgenic mouse model on vaccination with aggregated Aβ42. Clinical trials were terminated after four early reports of autoimmune meningoencephalitis, but a post-mortem study in one patient showed evidence of plaque reduction. Currently, no effective pharmacologic interventions have been researched enough to support their use in prevention of AD. Many epidemiological studies suggest that apolipoprotein E type 4 allele, diabetes, obesity, hypertension, and hyperlipidemia were associated the risk factor for late onset AD. Two key treatment approaches for AD have been driven by retrospective epidemiology: non-steroidal anti-inflammatory drugs and cholesterol-lowering statins. In both cases, the exact target in the disease cascade remains to be elucidated. In constant, only one acetylcholinesterase inhibitor, donepezil has been proven effective and used for patients with mild or moderate AD in Japan. Donepezil have demonstrated the effectiveness in stabilizing cognitive function and delaying behavioral symptoms. Given the likelihood that agents will become available that reliably delay onset and/or slow progression of AD, it will be important to detect preclinical AD as early as possible for maximal treatment effect. Cognitive function is generally examined by Mini-mental State Examination (MMSE), revised version of Hasegawa's Dementia Rating Scale (HDS-R) and Wechsler adult intelligence scale-revised (WAIS-R). The positron emission tomography or the single photon emission computed tomography were used for diagnosis of early stage AD. Caregivers should analyze behaviors and environmental factors which precede harmful abnormal conduct and try to avoid them.

Effects of Epitopes Combination and Adjuvants on Immune Responses to Anti-Alzheimer Disease DNA Vaccines in Mice

Alzheimer disease (AD) is a neurodegenerative disorder characterized by neuropathological hallmarks including deposits of the beta-amyloid peptide (AssP). Studies have shown that immunization with Abeta42 peptide reduces both the spatial memory impairments and Alzheimer disease-like neuropathologic changes in Alzheimer disease transgenic mice, but can cause side effect of a cell-mediated autoimmune meningoencephalitis. Recently, some studies showed that DNA vaccination could be used to generate an antibody response to Abeta without the adverse cell-mediated immune effect. In the current study, we generate four DNA vaccine plasmids (pV-GE1, pV-GE2, pV-GE3, and pV-GE4) against Alzheimer disease by separately fusing Abeta epitope sequences (coding for EFGH, DAEFGH, EFGH+EFGH, and EFGH+DAEFGH) with IgG heavy chain coding region of mouse. Meanwhile, the full-length gene Abeta encoding plasmid (pV-Abeta), empty vector (pVAX) and synthetic AssP were also included as control. The sera of BALB/c mice immunized via intramuscular with plasmids and peptide were tested by indirect ELISA for auto-AssP immunoreactivity. The results showed that all the DNA vaccine plasmids induced AssP-specific antibodies; moreover pV-GE2 and pV-Abeta constructs elicited higher antibody titers than other constructs (P < 0.05). To further enhance the immune response, GM-CSF encoding plasmid (pGM-CSF) and purified BCG-DNA were used as molecular adjuvants. BCG-DNA could enhance humoral and cellular immune responses simultaneously and did not alter the phenotype of the immune responses, whereas pGM-CSF showed no obvious effect on immune response. These results suggest that this immunization strategy of using Abeta epitope encoding plasmid plus BCG-DNA adjuvant may serve as the basis for developing anti-Alzheimer disease vaccines.