Serum Antineuronal Antibodies Research Articles

Neurological Diseases and Prevalence of Antineuronal Antibodies in Patients with Autoimmune Polyendocrine Syndrome Type 1 – A National Cohort Study

Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic disease caused by mutations in the autoimmune regulator gene. Although the disease-associated autoantibodies mostly target endocrine organs, autoantibodies from patients with APS-1 bind also to rat brain structures. The patients often have GAD65-antibodies, that can cause autoimmune encephalitis. However, neurological manifestations of APS-1 have not been systematically explored. We conducted a retrospective chart review on 44 Finnish patients with APS-1 (median age 38 years, 61% females) and collected all their neurological diagnoses. To assess the prevalence of serum antineuronal antibodies in APS-1, serum samples of 24 patients (median age 36 years, 63% females) were analyzed using a fixed cell-based assay. Of the 44 APS-1 patients, 10 (23%) had also received a diagnosis of a neurological disease. Of these neurological comorbidities, migraine (n = 7; 16%), central nervous system infections (n = 3; 7%), and epilepsy (n = 2; 5%) were the most prevalent. Other diagnoses recorded for single patients were axonal sensorimotor polyneuropathy, essential tremor, idiopathic intracranial hypertension, ischemic stroke, and trigeminal neuralgia. Serum antineuronal antibodies were detected in 42% of patients tested (10/24, 50% females, median age 42 years), GAD65 antibodies being the most common finding. Antibodies against glycine and aquaporin 4 were found in low titers. In four patients, relatively high titers of GAD65 antibodies without coexisting type 1 diabetes were found, but none presented with GAD65-encephalitis. Our study suggests an association between APS-1 and neurological disorders, the mechanisms of which are to be further investigated.

Investigation of anti-neuronal antibodies and disparity in central hypersomnias

Study objectivesMicrobial antigens can elicit an immune response leading to the production of autoantibodies cross-reacting with autoantigens. Still, their clinical significance in human sera in the context of brain diseases is unclear. Therefore, assessment of natural autoantibodies reacting with their neuropeptides may elucidate the autoimmune etiology of central hypersomnias. The study aims to determine whether serum autoantibody levels differ in patients with different types of central hypersomnias (narcolepsy type 1 and 2, NT1 and NT2; idiopathic hypersomnia, IH) and healthy controls and if the differences could suggest the participation of autoantibodies in disease pathogenesis. MethodsSera from 91 patients with NT1, 27 with NT2, 46 with IH, and 50 healthy controls were examined for autoantibodies against assorted neuropeptides. Participants were screened using questionnaires related to sleep disorders, quality of life, and mental health conditions. In addition, serum biochemical parameters and biomarkers of microbial penetration through the intestinal wall were determined. ResultsA higher prevalence of autoantibodies against neuropeptides was observed only for alpha-melanocytes-stimulating hormone (α-MSH) and neuropeptide glutamic acid-isoleucine (NEI), which differed slightly among diagnoses. Patients with both types of narcolepsy exhibited signs of microbial translocation through the gut barrier. According to the questionnaires, patients diagnosed with NT2 or IH had subjectively worse life quality than patients with NT1. Patients displayed significantly lower levels of bilirubin and creatinine and slightly higher alkaline phosphatase values than healthy controls. ConclusionsOverall, serum anti-neuronal antibodies prevalence is rare, suggesting that their participation in the pathophysiology of concerned sleep disorders is insignificant. Moreover, their levels vary slightly between diagnoses indicating no major diagnostic significance.

Increased neuropil antibody prevalence in COVID-19 patients with acute ischemic stroke

ABSTRACT Objectives COVID-19 infection is associated with an increased risk of acute ischemic stroke (AIS). Although the underlying mechanisms are largely unknown, autoimmunity has been implicated as a potential role player. Methods To investigate the presence and clinical impact of neuronal cell surface antibodies in COVID-19 associated AIS, patients with COVID-19 pneumonia and AIS (n = 30), COVID-19 pneumonia without AIS (n = 32) and AIS without COVID-19 infection (n = 27) were recruited. Serum anti-neuronal antibodies directed against well-characterized and novel cell surface antibodies were evaluated by cell-based assays and indirect immunohistochemistry, respectively. Results None of the recruited patients displayed well-characterized neuronal cell surface antibodies. Ten patients in the COVID-19 pneumonia with AIS group and three patients in the COVID-19 pneumonia without AIS group exhibited antibodies to neuropil of hippocampus and cerebellum. Neuropil-antibody positive patients showed trends towards milder clinical severity and reduced blood levels of inflammation factors. Conclusion Our results confirm the presence of neuropil antibodies in patients with COVID-19 infection and identify a putative antibody-driven association between AIS and COVID-19. The antigenic targets and potential pathogenic action of these antibodies need to be further explored.

Cerebellar antibodies in post-stroke sera of acute ischemic stroke patients

<p>Although serum anti-neuronal antibodies are found in acute ischemic stroke (AIS) patients, it is not completely clear whether they are already present before the cerebrovascular event or emerge thereafter.&nbsp;</p>. <p>Sera of 21 consecutive first-ever AIS patients were collected within the first day of AIS (baseline), as well as 1 and 6 months after AIS. Well-characterized and novel anti-neuronal antibodies were investigated by cell-based assays, immunoblotting and indirect immunohistochemistry.</p>. <p>None of the AIS sera collected at different time points showed well-characterized antibodies. In 7 patients, 1- and 6-month sera (but not baseline sera) showed IgG mostly reacting with soma and dendrites of cerebellar Purkinje cells. Antibody-positive patients did not differ in terms of clinical and etiological features.</p>. <p>Our results provide evidence for the antibody-triggering action of AIS. Although anti-cerebellar antibodies are not associated with the severity of stroke, they may potentially contribute to chronic post-stroke complications and disability.</p>.

Serum and Cerebrospinal Fluid Testing in Optic Neuropathy Patients with Malignant Tumors.

Purpose To evaluate the value of serum and cerebrospinal fluid (CSF) testing in optic neuropathy (ON) patients with malignant tumors. Methods Fourteen patients clinically diagnosed as ON with malignant tumors but without intracranial or orbital mass in MRI were included in this study. Detailed medical records including medical history, complete ophthalmic examination, colour fundus photography, visual field test, orbital MRI examination, serum and CSF testing data were collected and analyzed. The diagnosis of paraneoplastic optic neuropathy (PON) based on the 2004 recommended criteria of the paraneoplastic syndrome- Euronetwork consortium for paraneoplastic neurological disorders, and current adaption for neuropathies. All patients underwent serum tests for pathogens and autoantibodies including antinuclear antibodies, anticardiolipin antibodies, antineutrophil cytoplasmic antibodies, AQP4-Ab and MOG-Ab, as well as CSF tests for malignant cells under microscope. Serum paraneoplastic antibodies were detected in PON patients. Monkey cerebellar tissue-based assay was used to detect unknown serum anti-neuron antibodies in PON patients with negative paraneoplastic antibody testing results. Results Fourteen ON patients were classified as four groups based on their clinical and MRI characteristics, as well as serum and CSF testing results: [1] definite PON, 6 cases (11 eyes); [2] possible PON, 3 case (5 eyes); [3] meningeal carcinomatosis-associated optic neuropathy (MCON), 4 cases (6 eyes); [4] infiltrative optic neuropathy (ION), 2 cases (2 eyes). Malignant cells were found under microscope in CSF samples from MCON and ION patients, contrast to no malignant cells in CSF samples from PON cases. All 14 ON patients with malignant tumors showed negative results in serum tests for pathogens and autoantibodies. Serum paraneoplastic antibodies were tested in PON patients, anti- CV2, anti-Yo, and anti- amphiphysin were detected positive in 2, 1, and 1 case, respectively, in definite PON group, whereas no serum paraneoplastic antibody detected in possible PON group. Two unknown serum antineuronal antibodies (an anti- Purkinje cell antibody and an anti-granular cell antibody) were detected using monkey cerebellar tissue-based assay in 2 of 5 PON patients with negative paraneoplastic antibody test results. Conclusions Serum and CSF tests are of great importance in differentiating different subtypes of ON with malignant tumors. Current diagnosis of PON still depends on combination of clinical and MRI manifestations, as well as serum and CSF tests. Tissue-based assay may help to detect new biomarkers for ON etiology and diagnosis.

What Are the Biomarkers for Immunotherapy in SCLC?

Small-cell lung cancer (SCLC) is an aggressive malignancy that exhibits a rapid doubling time, a high growth fraction, and the early development of widespread metastases. The addition of immune checkpoint inhibitors to first-line chemotherapy represents the first significant improvement of systemic therapy in several decades. However, in contrast to its effects on non-SCLC, the advantageous effects of immunotherapy addition are modest in SCLC. In particular, only a small number of SCLC patients benefit from immune checkpoint inhibitors. Additionally, biomarkers selection is lacking for SCLC, with clinical trials largely focusing on unselected populations. Here, we review the data concerning the major biomarkers for immunotherapy, namely, programmed death ligand 1 expression and tumour mutational burden. Furthermore, we explore other potential biomarkers, including the role of the immune microenvironment in SCLC, the role of genetic alterations, and the potential links between neurological paraneoplastic syndromes, serum anti-neuronal nuclear antibodies, and outcomes in SCLC patients treated with immunotherapy.

Contribution of Immune-Mediated Paraneoplastic Syndromes to Neurological Manifestations of Neuroendocrine Tumours: A Retrospective Study

Introduction: Neurological symptoms associated with neuroendocrine tumours (NETs) may be related to metastatic disease or paraneoplastic syndromes (PNSs); these last are often associated with autoantibodies targeting various onconeural antigens. To better characterize neurological PNSs related to NETs, we report the largest case-series study to date. Methods: We retrospectively reviewed the charts of all patients diagnosed with NETs of the gastrointestinal tract who presented with neurological symptoms at either of 2 tertiary academic hospitals (Henri Mondor and Beaujon, France) between 1994 and 2016. All patients underwent extensive neurological tests including clinical, laboratory, and radiological investigations. The clinical response to immunomodulating agents was recorded. Results: In the 13 identified patients, the most common presentations were peripheral neuropathy (46.2%) and encephalopathy (26.6%). Of the 6 (53.3%) patients whose serum anti-neuronal antibodies were assayed, 5 had high titres. Short-term oral corticosteroid and immunosuppressant drug therapy was given to 4 of these patients, of whom 3 had a clinical response and 1 no response. Repeated high-dose intravenous immunoglobulin therapy induced a complete clinical response in 1 patient. Encephalopathy resolved fully after hepatectomy or intrahepatic chemoembolization for liver metastases in another 2 patients. Discussion: The neurological symptoms associated with NETs may be due in part to autoimmune PNS. Based on experience at our 2 centres, we estimate that autoimmune PNS occurs in about 1% of patients with NETs. Early symptom recognition allows the initiation of effective treatments including corticosteroids, immunosuppressive drugs, and/or intravenous immunoglobulins.

The prevalence and treatment outcomes of antineuronal antibody-positive patients admitted with first episode of psychosis.

Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined. To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive. Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy. Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four. A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery. None.

High prevalence and functional effects of serum antineuronal antibodies in patients with gastrointestinal disorders.

Antineuronal antibodies can be associated with both gastrointestinal (GI) and brain disorders. For example, antibodies against the potassium channel subunit dipeptidyl-peptidase-like protein-6 (DPPX) bind to neurons in the central nervous system (CNS) and myenteric plexus and cause encephalitis, commonly preceded by severe unspecific GI symptoms. We therefore investigated the prevalence of antineuronal antibodies indicative of treatable autoimmune CNS etiologies in GI patients. Serum samples of 107 patients (Crohn's disease n=42, ulcerative colitis n=16, irritable bowel syndrome n=13, others n=36) and 44 healthy controls were screened for anti-DPPX and further antineuronal antibodies using immunofluorescence on rat brain and intestine and cell-based assays. Functional effects of high-titer reactive sera were assessed in organ bath and Ussing chamber experiments and compared to non-reactive patient sera. Twenty-one of 107 patients (19.6%) had antibodies against the enteric nervous system, and 22 (20.6%) had anti-CNS antibodies, thus significantly exceeding frequencies in healthy controls (4.5% each). Screening on cell-based assays excluded established antienteric antibodies. Antibody-positive sera were not associated with motility effects in organ bath experiments. However, they induced significant, tetrodotoxin (TTX)-insensitive secretion in Ussing chambers compared to antibody-negative sera. Antineuronal antibodies were significantly more frequent in GI patients and associated with functional effects on bowel secretion. Future studies will determine whether such antibodies indicate patients who might benefit from additional antibody-directed therapies. However, well-characterized encephalitis-related autoantibodies such as against DPPX were not detected, underlining their rarity in routine cohorts.

Lack of serum antineuronal antibodies in children with autism.

Autism spectrum disorders (ASDs) are a severe group of neurodevelopmental disorders that are characterized by impairment in social communication, and imagination and social interaction. The aetiology of autism is complex, but some studies suggest autoimmunity to the central nervous system in the pathogenesis. The aim of this study is to investigate the positivity of antineuronal antibodies including anti-glutamic acid decarboxylase antibodies (anti-GAD), anti-glutamate receptor (anti-GluR) antibodies and seven types of anti-ganglioside antibodies, in children with autism. We conducted the study over a period of one year from May 2012 to December 2013. Human anti-GAD in serum were investigated with ELISA; human autoantibodies against the N-methyl-D-aspartate subtype of GluR were investigated with indirect immunofluorescence test; class IgG antibodies against the seven gangliosides were investigated with immunoblot assay. Serum antineuronal antibodies were measured in 42 children (24 male, 18 female) with autism in comparison to 21 (13 male, 8 female) healthy-matched children aged between 2-12 years. There was no seropositivity of antineuronal antibodies in either of the groups. There is no evidence to support an association between autism and antibodies positivity of anti-GAD, anti-GluR and anti-gangliosides (Ref. 26).

Oxidative Stress in Egyptian Children with Autism: Relation to Autoimmunity

Introduction Oxidative stress has been implicated in the pathogenesis of major psychiatric disorders, as the brain has comparatively greater vulnerability to oxidative damage Objectives and Aims We are the first to study the relationship between oxidative stress (by measuring plasma F2-isoprostane, as a marker of lipid peroxidation, and glutathione peroxidase, as an antioxidant enzyme) and autoimmunity (as indicated by serum antineuronal antibodies). Methods We studied these markers in a group of 44 Egyptian autistic children and 44 healthy matched-children. Results Our results showed that oxidative stress was found in 88.64% of autistic children. Oxidative stress, resulting from elevated plasma F2-isoprostane and/or reduced glutathione peroxidase, had significant risk for antineuronal positivity, which was found in 54.5% of autistic children, (odds ratio: 12.38 and 6.43, respectively, confidence interval: 1.37–112.10 and 1.21–34.19, respectively). Conclusions the strong association between oxidative stress and autoimmunity in autistic children may indicate the possible role of oxidative stress, through induction of autoimmunity, in some autistic patients. Therefore, studies considering the role of antioxidants and immunotherapy in amelioration of autistic manifestations are recommended.

Anti-Neuronal Antibodies in Patients with Fragile X Syndrome: Is there a Role of Autoimmunity in Its Pathogenesis?

Background: Fragile X syndrome (FXS) is a single-gene disorder with a broad spectrum of involvement, including cognitive and behavioural impairments of varying degrees with specific physical features and a strong association with autism. Objectives: In this study, the frequency of serum anti-neural antibodies was investigated in FXS patients who did and those who did not manifest autism spectrum disorders (ASD) in comparison to typically developing controls. Methods: The study involved 23 males (mean age, 19.78 ± 6.56 years) who harboured a full mutation in the FMR1 gene. The control group comprised 19 healthy students (mean age 24.63 ± 1.89 years). Serum anti-neuronal antibodies were analyzed using Western blotting. Results: Serum anti-neuronal antibodies were present in 10/23 (43.48%) FXS males. Conclusion: Serum anti-neuronal antibodies were found in a subgroup of FXS patients. Autistic symptoms in FXS may, in part, be caused by auto-immune factors. Further studies in larger patient and control groups are necessary to elucidate the aetiopathogenic role of anti-neuronal antibodies in FXS patients.

Non-paraneoplastic Autoantibody-negative Limbic Encephalitis Characterized by Mild Memory Impairment: A Case Report

Encephalitis that primarily involves limbic system structures such as the hippocampus and parahippocampal gyrus has been described in early papers, most commonly characterized by a subacute progressive impairment of short-term memory, psychiatric features and seizures. While these findings might be caused by viral infections or systemic autoimmune disorders, many patients with limbic encephalitis have an immune-mediated etiology (paraneoplastic or not) characterized with serum or CSF antineuronal antibodies. This case reports about non-paraneoplastic autoantibody-negative limbic encephalitis in which there are no detection of antigens and no evidence of tumors. Received: August 22, 2014 Revision received: September 2, 2014 Accepted: September 2, 2014

Serum anti-neuronal antibodies in amyotrophic lateral sclerosis

We aimed to investigate various anti-neuronal antibodies in sera of amyotrophic lateral sclerosis (ALS) patients to detect possible autoimmune encephalitis patients imitating ALS findings and to delineate the validity of routine screening of well-characterized anti-neuronal antibodies in ALS. The patients fulfilling the revised El Escorial diagnostic criteria for definite ALS were included. Their serum samples were investigated for antiganglioside (IgM/IgG) and onconeural (IgG) antibodies by immunoblotting, for ion channel antibodies (IgG) by a cell-based assay and for IgG binding patterns to the rat brain by indirect immunohistochemistry. Thirty-five patients with definite ALS and 30 healthy individuals were included. Ganglioside antibodies were detected in 2 out of 35 (5.7%) patients with ALS. The onconeural and ion channel antibodies were negative in our series. Varied serum IgG binding patterns were identified in eight (22.9%) patients. Although autoimmune encephalitis patients may occasionally present with atypical motor neuron disease findings, definite ALS patients do not appear to exhibit onconeural or ion channel antibodies, suggesting that routine analysis of these antibodies in typical ALS is not mandatory. By contrast, some ALS patients display anti-neuronal antibodies against undetermined target antigens, prompting investigation of these novel antibodies with more advanced methods.

Antigens diagnoses in paraneoplastic neurological syndromes.

10582 Background: At present, paraneoplasmatic neurological syndroms (PNS) are thought to be autoimmunological disorders. Neurological symptoms in PNS result from the disturbance of the nervous system, with a participation of the immune response triggered by the aberrant expression of the so-called onconeuronal antigens of a tumour. Very important for PNS diagnostics is the investigation of antineuronal antibodies (ANA) in the serum. Different types of ANA are frequently associated with specific tumors and with specific neurological syndromes.Investigations of serum ANA in patients with breast cancer with the symptoms of PNS. Methods: Investigations of ANA in serum were performed with the indirect immunofluorescence test but the type of ANA was analyzed by the Western Blot (WB) method . The presence of these antibodies which are included to the group of “the so called well characterized” is believed to be a definite (95 – 100%) determinant of the PNS diagnosis. Results: We examined 147 patients with breast cancer suspected to have PNS, hospitalized at Breast Cancer Clinic of the Institute of Oncology in Warsaw. The immunofluorescence test was positive in 92 patients, however in 24 patients the WB occurrence of “the well characterized” antibodies was found. In this group we observed: in 4 patients the cerebellar degeneration (anti-Yo, anti-Ma2); in 6 patients brainstem encephalitis and encephalomyelitis combined with sensory neuropathy (anti-Ma2, anti-CV2, anti-Yo, anti-Hu, anti-Ri); 4 myastenic syndrome (anti-Hu,anti-Ri,anti-Ma2/Ta); 5 sensory neuropathy (anti-Hu, anti-Yo, anti-Ma2, anti-Ri); and in single cases we also observed polyneuropathy: Guillain-Barre (Ma2): Miller-Fisher syndrom (anti-Ma2/Ta); cancer-associated retinopathy (anti-Yo); dermatomyositis (anti-Ri) and scleroderma (anti-Yo). Conclusions: Our analysis indicates that the investigation of the presence of ANA in the serum is the important in the diagnosis of PNS in patients with breast cancer. The types of ANA correspond to the individual paraneoplastic neurological syndromes which opens the proper methods of treatment in PNS.

The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children

BackgroundAutism may involve an autoimmune pathogenesis. Immunotherapy may have a role in autistic children who have brain auto-antibodies. AimThis study aimed to investigate the frequency of serum antineuronal auto-antibodies, as indicators of the presence of autoimmunity to brain, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism. MethodsSerum antineuronal antibodies were measured, by indirect immunofluorescence technique, in 80 autistic children, aged between 6 and 12 years, in comparison to 80 healthy-matched children. The severity of autism was assessed by using the Childhood Autism Rating Scale. ResultsAutistic children had significantly higher percent positivity of serum antineuronal antibodies (62.5%) than healthy controls (5%), P<0.001. The frequency of the positivity of serum antineuronal antibodies was significantly higher in children with severe autism (87.5%) than children with mild to moderate autism (25%), P<0.001. Similarly, the frequency of the positivity of these antibodies was significantly higher in female children with autism (90%) than male autistic children (53.3%), P=0.001. ConclusionsSerum antineuronal antibodies were found in a subgroup of autistic children and they were significantly correlated to the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the etiopathogenic role of antineuronal antibodies in autism. The role of immunotherapy in autistic patients, who are seropositive for antineuronal antibodies, should also be studied.

Paraneoplastic Opsoclonus-Myoclonus Syndrome as a New and Single Manifestation of Relapsing Disease in a Patient with Small Cell Lung Cancer

A 55-year-old woman smoker with a history of cough, weight loss, and chest pain, without neurologic complaints, presented with a mass in the right lung. A bronchoscopy revealed a tumor in the right intermediate bronchus. The biopsy of the lesion showed small cell carcinoma. A FDGpositron emission tomography (PET)-computed tomography (CT) scan was performed and is displayed in Figure 1A. A brain CT was normal. After the diagnosis of limited-stage small cell lung cancer, the patient was treated with four cycles of cisplatin and etoposide combined with normofractionated thoracic radiotherapy (55 Gy) concurrent with the last two cycles. A radiological complete response was assessed, and treatment was completed with prophylactic cranial irradiation. Seven months after complete response, the patient experienced rapidly progressive dizziness and gait instability, followed by gaze disturbances and involuntary, continuous, conjugate, and chaotic saccadic eye movements. The gait disorder worsened, leaving the patient absolutely bedridden. On examination, intermittent myoclonic movements were apparent in the limbs and trunk (see video, part 1, Supplemental Digital Content 1, http://links.lww.com/JTO/A73, which shows these findings). She had neither cognitive impairment nor motor/sensory losses. Brain magnetic resonance imaging and cerebrospinal fluid examination were without noteworthy alterations. Serum antineuronal antibodies (antiHu, anti-Ri, anti-CV2, and antiamphiphysin) were negative. She was diagnosed with opsoclonus-myoclonus syndrome (OMS), and intravenous corticoids were administered for 5 days without improvement. There was no evidence of relapse on the chest CT, and the patient refused a bronchoscopy. A positron emission tomography-CT examination was strictly normal (Figure 1B). Although there was no visible tumor, we considered OMS as its herald, and second-line chemotherapy was started with carboplatin and etoposide in an attempt to reverse her devastating neurologic condition. After just the first cycle, opsoclonus and gait instability improved and the myoclonus resolved completely (see video, part 2, Supplemental Digital Content 1, http://links.lww.com/JTO/A73, which demonstrates her clinical improvement). The patient has completed three cycles of chemotherapy and continued free of recurrence for a total of 31 months, when a right supraclavicular relapse was detected and pathologically confirmed. Nevertheless, paraneoplastic neurologic symptoms did not recur, and third-line chemotherapy with oral topotecan was started.

Acute disseminated encephalomyelitis with medial temporal lesions mimicking acute limbic encephalitis

We describe a 59-year-old Japanese man with acute disseminated encephalomyelitis (ADEM) demonstrating medial temporal lesions on magnetic resonance images (MRI) mimicking acute limbic encephalitis. This patient had antecedent infection and developed urinary retention. Subsequently he showed various neurological manifestations including truncal ataxia, nystagmus and generalized convulsions, suggesting multifocal brain and spinal cord lesions. Brain MRI demonstrated hyperintensity areas restricted to the left hippocampus, amygdala, and inferior temporal gyrus. The cerebrospinal fluid did not show any pleocytosis or elevated protein levels, and had no evidence of herpes virus infection. Serum antineuronal antibodies were not identified. Corticosteroid therapy markedly improved the symptoms. Although these clinical features indicating multifocal central nervous system lesions were compatible with those of ADEM, none of the previously reported patients with ADEM showed lesions confined to the medial temporal lobes mimicking acute limbic encephalitis. Medial temporal lesions are characteristic features of herpetic or non-herpetic acute limbic encephalitis. Findings in our patient suggest that non-herpetic limbic encephalitis patients showing marked response to

Oxidative stress in Egyptian children with autism: relation to autoimmunity

We are the first to study the relationship between oxidative stress (by measuring plasma F2-isoprostane, as a marker of lipid peroxidation, and glutathione peroxidase, as an antioxidant enzyme) and autoimmunity (as indicated by serum antineuronal antibodies) in a group of 44 Egyptian autistic children and 44 healthy matched-children. Our results showed that oxidative stress was found in 88.64% of autistic children. Oxidative stress, resulting from elevated plasma F2-isoprostane and/or reduced glutathione peroxidase, had significant risk for antineuronal positivity, which was found in 54.5% of autistic children, (odds ratio: 12.38 and 6.43, respectively, confidence interval: 1.37–112.10 and 1.21–34.19, respectively). Conclusions: the strong association between oxidative stress and autoimmunity in autistic children may indicate the possible role of oxidative stress, through induction of autoimmunity, in some autistic patients. Therefore, studies considering the role of antioxidants and immunotherapy in amelioration of autistic manifestations are recommended.

Antineuronal antibodies and electroneurophysiological studies in pediatric patients with neuropsychiatric systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most difficult manifestations of lupus to diagnose. Measurement of serum brain autoantibodies and assessment of cognitive function by electroneurophysiological studies (electroencephalogram (EEG) and P300) have contributed to an earlier and a more specific diagnosis of NPSLE. Thus, we were stimulated to assess the value of serum antineuronal antibodies and electroneurophysiological studies in diagnosis and early prediction of NPSLE. To investigate this, assessment of serum antineuronal antibodies and cognitive function (clinically and by electroneurophysiological studies) was done in 30 lupus patients [14 (46.7%) with and 16 (53.3%) without clinical evidence of NPSLE] in comparison with 30 healthy matched subjects. Patients without clinical evidence of NPSLE were followed-up clinically by monthly neuropsychiatric evaluation for 18 months. Seropositivity for antineuronal antibodies and abnormalities of EEG and P300 (prolonged latency and/or low amplitude) were found in 60%, 50% and 70%, respectively of lupus patients. During follow-up, 8 out of the 16 patients without clinical evidence of NPSLE developed such evidence [six (75%) had antineuronal seropositivity, five (62.5%) had abnormal EEG, six (75%) had P300 abnormalities and all had at least one abnormal result of these parameters at the time of initial evaluation before clinical presentation of NPSLE]. In conclusion, serum antineuronal antibodies and electroneurophysiological studies may be reliable parameters for diagnosis and early prediction of NPSLE, especially when combined together, before clinical manifestations ensue. Further studies on a large scale are warranted to evaluate the predictive value of these parameters in NPSLE.