Clinical relevance of distinguishing autoimmune nodopathies from CIDP: longitudinal assessment in a large cohort.

BACKGROUND: The aim of this study was to determine treatment response and whether it is associated with antibody titre change in patients with autoimmune nodopathy (AN) previously diagnosed as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and to compare clinical features and treatment response between AN and CIDP. METHODS: Serum IgG antibodies to neurofascin-155 (NF155), contactin-1 (CNTN1) and contactin-associated protein 1 (CASPR1) were detected with cell-based assays in patients diagnosed with CIDP. Clinical improvement was determined using the modified Rankin scale, need for alternative and/or additional treatments and assessment of the treating neurologist. RESULTS: We studied 401 patients diagnosed with CIDP and identified 21 patients with AN (10 anti-NF155, 6 anti-CNTN1, 4 anti-CASPR1 and 1 anti-NF155/anti-CASPR1 double positive). In patients with AN ataxia (68% vs 28%, p=0.001), cranial nerve involvement (34% vs 11%, p=0.012) and autonomic symptoms (47% vs 22%, p=0.025) were more frequently reported; patients with AN improved less often after intravenous immunoglobulin treatment (39% vs 80%, p=0.002) and required additional/alternative treatments more frequently (84% vs 34%, p<0.001), compared with patients with CIDP. Antibody titres decreased or became negative in patients improving on treatment. Treatment withdrawal was associated with a titre increase and clinical deterioration in four patients. CONCLUSIONS: Distinguishing CIDP from AN is important, as patients with AN need a different treatment approach. Improvement and relapses were associated with changes in antibody titres, supporting the pathogenicity of these antibodies.

[Cerebellar antibodies in post-stroke sera of acute ischemic stroke patients]. / Kisagyi antitestek akut ischaemiás stroke-on átesett betegek szérumában.

Background and purpose:

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. 

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.

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.

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.

Follow-up of patients with epilepsy harboring antiglycine receptor antibodies.

OBJECTIVE: The long-term follow-up of patients with epilepsy harboring autoantibodies against the glycine receptor (also glycine receptor antibodies or GlyR-Ab) is not well-known. Our aim was to investigate the 5-year prognosis and treatment response of patients with epilepsy who were seropositive for GlyR-Ab. METHODS: Clinical features; electroencephalogram (EEG), neuroradiological, and neuropathological findings; and treatment responses of patients with epilepsy with GlyR-Ab seropositivity were investigated. RESULTS: Thirteen (5.46%) of 238 patients with epilepsy were GlyR-Ab positive: focal epilepsy of unknown cause (FEoUC) was diagnosed in four (7.27%) out of 55 patients, mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) in five (4.5%) out of 111 patients, epileptic encephalopathy (EE) in two (4%) out of 50 patients, and status epilepticus (SE) in two (9.09%) out of 22 patients. None of the patients developed any other neurological symptoms or cancer during the 5-year follow-up. Seven of them had seizures that were resistant to antiepileptic drug (AED). Immunotherapy was used in two patients (with FEoUC and EE) improving seizure control. Three patients with MTLE-HS benefited from epilepsy surgery, and another patient with EE showed spontaneous remission. CONCLUSION: Glycine receptor antibodies are detected in a wide spectrum of epileptic disorders with unclear pathogenic significance. Two GlyR-Ab seropositive patients with AED-resistant epilepsy treated with intravenous immunoglobulin (IVIg) showed clear benefit from immunotherapy. Future studies will be valuable in determining the role of screening patients with drug-resistant epilepsy for GlyR-Ab in order to identify patients who may benefit or respond to immunotherapy.

Effects of in vivo and in vitro administration of neuro-Behcet's disease IgG.

Antibodies directed against membrane antigens of neuronal axonal processes (neuropil) have been recently identified in neuro-Behcet's disease (NBD) patients. To delineate the potential pathogenic action of these antibodies, pooled sera from seven NBD patients with neuropil antibodies and seven healthy controls were divided into purified IgG and IgG-depleted serum (IgG-DS) fractions and each fraction was administered into lateral ventricles of rats. NBD IgG-injected rats showed reduced locomotor activity in the open field test as compared to NBD IgG-DS, healthy control IgG, healthy control IgG-DS and PBS injected rats (n = 10 for each group). There were no significant differences among treatment groups by means of anxiety-like behaviors (assessed by elevated plus maze test) and learning/memory functions (assessed by passive avoidance test). Administration of NBD IgG on cultured SH-SY5Y neuroblastoma cells induced significantly increased cell death and apoptosis (as measured by nucleosome levels in the supernatants) as compared to other treatment groups. Our results suggest that IgGs isolated from sera of neuropil antibody-positive NBD patients have a neurotoxic action, which is presumably mediated by apoptotic mechanisms. Motor deficits frequently observed in NBD patients might at least partially be caused by the pathogenic action of anti-neuronal IgG.

Glial and neuronal antibodies in patients with idiopathic intracranial hypertension.

Headache and visual disturbances are the main presenting symptoms of idiopathic intracranial hypertension (IIH) characterized by increased intracranial pressure (ICP) with an unknown cause. We aimed to investigate the antibodies against optic neuritis-associated glial antigens, aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) and uncharacterized neuronal membrane antigens in IIH patients. Consecutive patients diagnosed according to Friedman revised diagnostic criteria and control subjects were included after their consent. All serum samples were analyzed for antibodies against AQP4 and MOG using cell-based immunofluorescent assays and for uncharacterized neuronal membrane antigens by indirect immunocytochemistry utilizing live neurons. Sera of 34 patients with IIH and 40 control subjects were investigated but none of the patients showed AQP4 and MOG antibodies. However, serum IgG of five IIH patients showed reactivity against membrane antigens of rat hippocampal and cortical neurons. Interestingly, three out of these five patients had nonspecific white matter lesions on MRI, whereas only four of all other patients had these lesions (p = 0.048). AQP4 and MOG antibodies do not seem to have a role in the pathophysiology of IIH. However, association of immunocytochemistry findings with the presence of white matter lesions may suggest that immunological factors contribute to the pathogenesis of IIH in at least some of the patients.

Neuronal autoantibodies in mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: Our aim was to investigate the prevalence of neuronal autoantibodies (NAbs) in a large consecutive series with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) and to elucidate the clinical and laboratory clues for detection of NAbs in this prototype of frequent, drug-resistant epilepsy syndrome. METHODS: Consecutive patients diagnosed with MTLE fulfilling the MRI criteria for HS were enrolled. The sera of patients and various control groups (80 subjects) were tested for eight NAbs after ethical approval and signed consents. Brain tissues obtained from surgical specimens were also investigated by immunohistochemical analysis for the presence of inflammatory infiltrates. The features of seropositive versus seronegative groups were compared and binary logistic regression analysis was performed to explore the differentiating variables. RESULTS: We found antibodies against antigens, contactin-associated protein-like 2 in 11 patients, uncharacterised voltage-gated potassium channel (VGKC)-complex antigens in four patients, glycine receptor (GLY-R) in 5 patients, N-methyl-d-aspartate receptor in 4 patients and γ-aminobutyric acid receptor A in 1 patient of 111 patients with MTLE-HS and none of the control subjects. The history of status epilepticus, diagnosis of psychosis and positron emission tomography or single-photon emission CT findings in temporal plus extratemporal regions were found significantly more frequently in the seropositive group. Binary logistic regression analysis disclosed that status epilepticus, psychosis and cognitive dysfunction were statistically significant variables to differentiate between the VGKC-complex subgroup versus seronegative group. CONCLUSIONS: This first systematic screening study of various NAbs showed 22.5% seropositivity belonging mostly to VGKC-complex antibodies in a large consecutive series of patients with MTLE-HS. Our results indicated a VGKC-complex autoimmunity-related subgroup in the syndrome of MTLE-HS.

Switch-associated protein 70 antibodies in multiple sclerosis: possible association with disease progression.

OBJECTIVE: This study was conducted to identify a biomarker for multiple sclerosis (MS) that can be used as a predictor of relapse and disability. MATERIALS AND METHODS: Sera of 26 consecutive relapsing-remitting MS (RRMS) patients were screened for switch-associated protein 70 (SWAP-70) antibody, which was previously identified by protein macroarray. The serum levels of several cytokines, chemokines and soluble adhesion molecules related to MS attacks were measured by enzyme-linked immunosorbent assay (ELISA). A possible correlation was sought among levels of SWAP-70 antibody, measured humoral factors and disability scores. RESULTS: ELISA studies showed high-titre SWAP-70 antibodies in 16 (61.5%) RRMS sera obtained during the attack period and 9 (34.6%) sera obtained during remission. There was a significant inverse correlation between SWAP-70 antibody levels and expanded disability status scale scores, CXCL10, soluble VCAM-1, CXCL13 and soluble VLA-4 levels. CONCLUSION: Our results showed that SWAP-70 antibodies could potentially be utilized as relapse and prognostic biomarkers in MS. Whether or not SWAP-70 antibodies have any effect on disease mechanisms requires further investigation.

CACNA1H antibodies associated with headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL).

BACKGROUND: Patients with the syndrome of headache with neurological deficits and lymphocytosis (HaNDL) typically present with recurrent and temporary attacks of neurological symptoms and cerebrospinal fluid lymphocytosis. AIM AND METHODS: To identify potential HaNDL-associated antibodies directed against neuronal surface and/or synapse antigens, sera of four HaNDL patients and controls were screened with indirect immunohistochemistry, immunofluorescence, cell-based assay, radioimmunoassay, protein macroarray and enzyme-linked immunosorbent assay (ELISA). RESULTS: Although HaNDL sera did not yield antibodies to any of the well-characterized neuronal surface or synapse antigens, protein macroarray and ELISA studies showed high-titer antibodies to a subunit of the T-type voltage-gated calcium channel (VGCC), CACNA1H, in sera of two HaNDL patients. CONCLUSION: Our results support the notion that ion channel autoimmunity might at least partially contribute to HaNDL pathogenesis and occurrence of neurological symptoms.

Anti-N-methyl-D-aspartate receptor encephalitis with minimal cortical impairment.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis has been recently identified as a fulminant encephalopathy, presenting with a variety of symptoms including behavioral change, amnesia and seizures suggesting cortical gray matter involvement. A 42-year-old woman presented with acute-onset clinical and magnetic resonance imaging (MRI) findings indicating brainstem and diencephalon involvement. Her neuropsychological examination revealed mild frontal dysfunction with no memory impairment. Detailed diagnostic workup proved negative except for serum/cerebrospinal fluid (CSF) NMDAR-antibodies and increased activity in inguinal and pelvic lymph nodes on positron-emission tomography (PET) examination. The symptoms and MRI findings completely resolved following steroid treatment. A 38-year-old woman presented with migraine-type headache and episodes of forgetfulness. Her brain MRI and neuropsychological examination were normal and diagnostic workup was unremarkable. N-methyl-D-aspartate receptor antibodies were identified in her sera and her symptoms spontaneously resolved within few months. Our cases suggest that anti-NMDAR encephalitis might present with minimal cognitive impairment, no apparent cortical gray matter involvement, a mild clinical course and without the classical clinical features of the disease.

Serum IgG of patients with relapsing inflammatory optic neuropathy immunoreacts with Sox2-positive glial cells of the optic nerve.

BACKGROUND: Given the significance of glial cells in maintenance of neurons, antibodies directed against glial cells of the optic nerve might reasonably be expected to have a pathogenic impact in relapsing inflammatory optic neuropathy (RION). METHODS: We investigated IgG immunoreactive with the optic nerve tissue by indirect immunohistochemistry using sera of 20 RION patients. Commercial Sox2-antibody was used for double immunolabeling. RESULTS: Serum IgG of 5 RION patients reacted with cells aligned in the interfascicular regions of the optic nerve. IgG binding sites significantly co-localized with the Sox2-antibody. CONCLUSION: Our results suggest that a subset of RION patients may harbor anti-glial antibodies.

Human-derived hair follicle stem cells and hydrogen sulfide on focal cerebral ischemia model: A comparative evaluation of radiologic, neurobehavioral and immunohistochemical results.

The present study investigated the effects of intracerebral human-derived hair follicle stem cells (HFBSCs), whether alone or in combination with hydrogen sulfide (H2S) in a rat model of focal cerebral ischemia. The rats were randomly assigned into 4 groups (n = 10): Control (phosphate buffered saline (PBS)), Group A (at 24 h post-middle cerebral artery occlusion(MCAo), stereotaxic intracerebral, 1,0 × 106, total 10 µL HFBSCs), Group B (3-14 d post-MCAo, intraperitoneal (i.p.), 25 µM/kg/day H2S), Group AB (HFBSCs + H2S). Cranial magnetic resonance images were recorded on postoperative 1st and 28th days. Three dimensional analysis was performed to calculate the infarct volumes. Rotarod and cylinder tests were performed after MCAo and finally all rats were euthanized by cardiac perfusion at 28 days after MCAo for immunohistochemical analysis. The reduction in infarct volumes of rats receiving HFBSC was significant. The cranial infarct volume on the postoperative 28th day was significantly higher in the group in which H2S was administered alone compared to the HFBSC alone group. All animals showed steadily improved spontaneous locomotor activity from day 7 post-MCAo on rotarod test, from day 1 on cylinder test, but showed no significant differences at all times. In all groups, the grading scores of CD34, CD5, CD11b and GFAP immunohistochemical markers did not differ significantly. In conclusion, intracerebral HFBSC treatment after 24 h of ischemic stroke may be an effective way to reduce the cranial infarct volume, whereas H2S treatment alone or in combination with HFBSC may not be sufficient for ischemic brain injury.

Switch-associated protein 70 antibodies in multiple sclerosis: relationship between increased serum levels and clinical relapse.

OBJECTIVE: To identify an antibody biomarker for multiple sclerosis (MS) that can be used as a predictor of MS relapses. METHODS: MS patients' sera were screened by a protein macroarray derived from human fetal brain cDNA library (hEX1). Sera of 90 consecutive relapsing remitting MS (RRMS) patients and age-matched 145 Behçet's disease (BD) patients, 40 infectious meningoencephalitis patients, and 70 healthy controls were screened by ELISA for serum antibodies against the selected clone. RESULTS: Sequencing of the clone with the highest signal intensity revealed switch-associated protein 70 (SWAP70) as a potential target autoantigen in RRMS. ELISA studies showed high-titer SWAP70-antibodies in 21 (23.3 %) RRMS and 7 (4.8 %) BD patients. SWAP70 antibodies were more likely to be found positive in sera obtained during or shortly after a relapse. CONCLUSION: Detection of SWAP70 antibodies during the attack period might suggest that SWAP70 is involved in MS relapse pathogenesis. Whether serum SWAP70 antibody detection may be utilized as an MS relapse predictor should be tested in prospective studies.

Kv5.1 antibody in epilepsy patients with unknown etiology.

BACKGROUND: Neuronal autoantibodies and favorable response to immunosuppressive treatment have been described in patients with chronic epilepsy of unknown cause, suggesting autoimmune etiology. Our aim was to identify novel epilepsy-specific autoantibodies reactive with neuronal surface antigens. METHODS: Sera of 172 epilepsy patients with unknown cause and 30 healthy controls were screened with indirect immunofluorescence to identify IgG reacting with primary rat neuronal cultures. Putative target autoantigens were investigated with immunoprecipitation (IP) and liquid chromatography-mass/mass spectrometry (LC-MS/MS) studies using SH-SY5Y cells. Validation of LC-MS/MS results was carried out by IP and immunocytochemistry assays. RESULTS: Antibodies to neuronal cell surface antigens were detected in 18 epilepsy patients. LC-MS/MS analysis identified voltage-gated potassium channel modifier subfamily F member 1 (KCNF1, Kv5.1) as the single common cell surface antigen in 4 patients with Lennox-Gastaut syndrome (n = 2), focal epilepsy of unknown cause (n = 1) and mesial temporal lobe epilepsy with hippocampal sclerosis (n = 1). These patients had the common features of early seizure onset and treatment-resistance. IP assays and co-localization (serum IgG and commercial Kv5.1-antibody) studies done with non-fixed Kv5.1-transfected HEK293 cells and primary neuronal cultures confirmed the presence of Kv5.1-antibody in 4 epilepsy patients identified by LC-MS/MS. Similar findings were not obtained by sera of other patients with epilepsy, patients with autoimmune encephalitis and healthy controls. CONCLUSION: The herein described novel neuronal surface antibody to Kv5.1 appears to be associated with treatment-resistant epilepsy of unknown cause. Exact clinical and pathogenic significance of this antibody remains to be elucidated.

Antineuronal antibodies in migraine patients with white matter lesions.

Magnetic resonance imaging (MRI) studies occasionally display focal hyperintense lesions within the white matter of migraine patients. No immunological factors associated with these lesions have been defined so far. To investigate the relationship between MRI lesions and antineuronal antibody response, 17 migraine patients with white matter lesions (WML), 19 migraine patients without WML, 20 multiple sclerosis patients with WML and with no headache history, and 20 healthy individuals were enrolled, and their sera were examined by indirect immunohistochemistry for the presence of immunoglobulin G (IgG) reacting with the rat brain tissue. Migraine patients with and without WML essentially showed identical demographic and clinical features and frequencies of systemic autoantibodies. However, migraine patients with WML displayed a significantly higher frequency of antineuronal antibodies than those without WML (12/17 vs. 2/19, p = .0004). Serum IgG of migraine patients predominantly reacted with the cytoplasm of neurons and the molecular layer of cerebellum. None of the multiple sclerosis patients and healthy controls displayed antineuronal antibodies. Our results imply the involvement of inflammation in migraine pathogenesis.

Autoantibodies to neuronal surface antigens in thyroid antibody-positive and -negative limbic encephalitis.

BACKGROUND: Thyroid antibodies (Thy-Abs) are frequently detected in various autoimmune disorders in coexistence with other systemic autoantibodies. In association with an encephalopathy, they are often taken as evidence of Hashimoto's encephalitis (HE). However, the presence of Thy-Abs in a cohort of limbic encephalitis (LE) patients and their association with anti-neuronal autoimmunity has not been explored. PATIENTS AND METHODS: We investigated thyroid and anti-neuronal antibodies in the sera of 24 LE patients without identified tumors by cell-based assay and radioimmunoassay and evaluated their clinical features. RESULTS: There was a female predominance in Thy-Ab-positive LE patients. Five of the eight Thy-Ab-positive patients and six of the 16 Thy-Ab-negative patients had antibodies to voltage-gated potassium channel (VGKC), N-methyl-D-aspartate receptor (NMDAR) or undefined surface antigens on cultured hippocampal neurons. There were trends towards fewer VGKC antibodies (1/8 vs. 5/16, P = 0.159) and more NMDAR antibodies (2/8 vs. 1/16, P = 0.095) among the Thy-Ab-positive LE patients; antibodies to undefined surface antigens were only identified in Thy-Ab-positive patients (2/8 vs. 0/16, P = 0.018). There were no distinguishing clinical features between Thy-Ab-positive patients with and without neuronal antibodies. However, patients with anti-neuronal antibodies showed a better treatment response. CONCLUSION: Thy-Abs can be found in a high proportion of patients with non-paraneoplastic LE, often in association with antibodies to specific or as yet undefined neuronal surface antigens. These results suggest that acute idiopathic encephalitis patients with Thy-Abs should be closely monitored for ion-channel antibodies and it should not be assumed that they have HE.

Association of the kynurenine pathway metabolites with clinical, cognitive features and IL-1ß levels in patients with schizophrenia spectrum disorder and their siblings.

OBJECTIVE: There is evidence suggesting that tryptophan (TRP)-kynurenine (KYN) pathway dysregulation is involved in the pathophysiology of schizophrenia and is regulated by inflammatory cytokines. The study investigate for the first time whether this dysregulation occurs in advanced stages of the disease as a byproduct or emerges as one of the early and inherited manifestations of schizophrenia. METHOD: Sera of 148 patients with schizophrenia spectrum disorders (SCZ), 139 unaffected siblings (SIB) and 210 controls were investigated. Serum interleukin (IL)-1ß levels were measured by ELISA, and TRP, KYN and kynurenic acid (KYNA) levels were measured by a high-performance liquid chromatography system. Also, we collected clinical data by applying Comprehensive Assessment of Symptoms and History in SCZ, and SIS-R in SIB and control groups. RESULTS: Compared to controls, SCZ and SIB groups had lower TRP and higher KYNA levels. TRP levels showed significant differences only between SCZ and controls (p < 0.01). KYNA levels of both SCZ (p ≤ 0.001) and SIB (p < 0.05) were higher than controls. No statistical significance was found for KYN levels across groups. SCZ and SIB groups had higher serum IL-1ß levels than controls (p ≤ 0.001). CONCLUSIONS: Patients with SCZ and their siblings exhibited similar clinical features and TRP metabolite levels suggesting that TRP-KYN dysregulation may be an inherited component of the disease putatively conferring increased risk to schizophrenia. Elevation of IL-1ß is one of the factors promoting overconsumption of the TRP-KYN pathway leading to increased production of neuroregulatory KYNA and presumably to neurodegeneration.

Enhanced NLRP3 and DEFA1B Expression During the Active Stage of Parenchymal Neuro-Behçet's Disease.

BACKGROUND/AIM: Neurological symptoms (neuro-Behçet's disease; NBD) occur in a fraction of Behçet's disease (BD) patients and often present with parenchymal brain lesions and clinical exacerbations. Our aim was to identify genes associated with attack and remission periods of NBD. MATERIALS AND METHODS: Microarray analysis was performed using peripheral blood mononuclear cell (PBMC) samples obtained during attack and remission periods of five NBD patients. Expression levels of the most significantly up-regulated genes were measured with real-time PCR using PBMC samples of 15 NBD patients and 20 healthy controls. RESULTS: During NBD attacks, the most remarkably up-regulated genes were defensin alpha 1B (DEFA1B) and NLR family, pyrin domain containing 3 (NLRP3). Real time PCR studies showed significantly increased DEFA1B and NLRP3 expression levels during attacks. CONCLUSION: Immunological factors showing the most significant increase in expression during NBD attacks were primarily associated with innate immunity functions. DEFA1B and NLRP3 can be used as biomarkers for estimation of disease activity in NBD.

Assessment of the MRI and Behavioral Test Results in a Focal Cerebral Ischemia-Reperfusion Model in the Rat after Separate and Combined Use of Mouse-Derived Neural Progenitor Cells, Human-Derived Neural Progenitor Cells and Atorvastatin.

AIM: To assess the efficacy of Neural progenitor cell (NPC) transplantation in ischemic stroke, and to investigate whether atorvastatin enhances therapeutic potency of NPC after stroke. MATERIAL AND METHODS: The focal cerebral ischemia-reperfusion model was performed by transient occlusion of middle cerebral artery. Rats were assigned randomly to receive intracerebral transplantation of mouse NPC alone (mNPC), human NPC alone (hNPC), mouse NPC plus oral atorvastatin (mNPC+A), human NPC plus oral atorvastatin (hNPC+A), oral atorvastatin alone, or intracerebral Dulbecco"s Modified Eagle"s medium injection (control group). Adhesive removal, rotarod, cylinder tests, and magnetic resonance imaging (MRI) were used for assessment of rats during 4 weeks. After sacrification on 28th day, rats were investigated by immunofluorescent staining. RESULTS: The hNPC and mNPC groups showed significantly improved functional outcome and reduced infarct area ratio compared with the control group. The hNPC group had significantly better performance and lower infarct area ratio than the mNPC group. Addition of atorvastatin to stem cell therapy significantly improved functional outcome, although it did not affect the infarct area ratio on MRI. Anti-inflammatory response in the infarct area was higher in the mNPC group. NPC transplantation significantly reduced the amount of microglia and a significant increase in the amount of astrocytes. CD8a+ T lymphocyte and granzyme B activities were not detected in any of the subjects. CONCLUSION: Both hNPC and mNPC treatments significantly improved functional outcome, and reduced infarct area ratio after stroke. Atorvastatin enhanced the therapeutic potency of NPCs, including neurological improvement.

Investigation of neuronal auto-antibodies in children diagnosed with epileptic encephalopathy of unknown cause.

AIM: Cryptogenic forms of epileptic encephalopathies (EE) with their well-known features of drug-resistance, mental deterioration and partial response to immunotherapies are ideal candidates for screening for neuronal autoantibodies (NAA). METHOD: Fifty consecutive pediatric patients with a diagnosis of EE of unknown cause were included. Nine NAAs were tested by ELISA, RIA or cell-based assays. Clinical features of seronegative and seropositive patients were compared. RESULTS: NAAs were found in 7/50 (14%) patients. They were N-methyl-d-aspartate receptor in two (4%), glycine receptor in two (4%), contactin-associated protein-like 2 in one (2%), glutamic acid decarboxylase in one (2%) and type A gamma aminobutyric acid receptor in one patient (2%). Furthermore, serum IgGs of two patients negative for well-characterized NAAs, showed strong reactivity with the uncharacterized membrane antigens of live hippocampal neurons. There were no significant differences between seropositive and seronegative patients by means of epilepsy duration, anti-epileptic drug resistance, EE type, types of seizures, seizure frequencies, EEG features or coexisting autoimmune diseases. Some seropositive patients gave good-moderate response to immunotherapy. DISCUSSION: Potential clues for the possible role of autoimmunity in seropositive patients with EE were atypical prognosis of the classical EE type, atypical progression and unusual neurological findings like dyskinesia.

Investigation of anti-neuronal antibodies in status epilepticus of unknown etiology: a prospective study.

There have been recent reports of antibody-mediated status epilepticus. The objective of our study was to investigate the prevalence of neuronal autoantibodies in patients with status epilepticus (SE) with unresolved etiology. The presence of neuronal autoantibodies was investigated prospectively in adult patients with SE who presented to our clinic between February 2012 and December 2013 with unresolved etiology. Clinical and electrophysiologic features of seropositive patients were recorded. Also, seronegative and seropositive patient groups were compared in terms of demographic and clinical features, treatment responses, and outcomes. Neuronal antibodies against N-methyl-D-aspartate receptor (NMDA-R) were positive in 2 patients, against glycine receptor (Gly-R) in 2 patients, and against gamma-aminobutyric acid-A receptor [GABA(A)R] in 1 patient, which constituted a total of 5 (22.7%) of 22 patients with SE with unidentified etiology. One of three patients with systemic tumors was positive for GABA(A)R antibody. Four patients had a short epilepsy duration, while one of the NMDA-R antibody-positive patients had chronic epilepsy and double cortex finding in MRI. There was no significant difference between seropositive and seronegative patient groups in terms of demographic and clinical features, treatment responses, and outcomes. Neuronal antibodies are found in a sizeable portion of de novo SE patients, who are potential candidates of autoimmune encephalitis. Alternatively, these antibodies may presumably also emerge in SE patients with a chronic epilepsy history as an epiphenomenon. Further research is required to make the distinction between these two different antibody formation mechanisms.