Anti-basal Ganglia Antibodies Research Articles

The Prevalence of Streptococcal Infection and Anti-Basal Ganglia Antibodies in ADHD Pediatric Patients

Children who have trouble paying attention, controlling their impulses, or being hyperactive may suffer from attention-deficit/hyperactivity disorder (ADHD), a mental health condition that is largely influenced by their genes. However, other factors in their surroundings, such as exposure to certain bacteria or toxins, may also play a role in triggering or worsening their symptoms. In our study, we wanted to find out how common it is for children with ADHD to have an infection caused by a type of bacteria called group A streptococcus (GAS), and how often they have antibodies against GAS (ABGA) in their blood, which may indicate a past or ongoing infection. 60 children took part in a trial that was open, controlled, and random. They were split into two equal groups: group A had children with ADHD and group B had healthy children. We collected their demographic data such as age, sex, and ADHD risk factors. Group A had children with ADHD. Only depression was much higher in GAS+children than GAS-children (P=0.035). Other factors like attention, impulsiveness, non-planning, motor and fine motor speed were not different between GAS+ and GAS-children. Group B had healthy children. Impulsiveness and depression were much higher in GAS+children than GAS-children (P=0.001, 0.001). Other factors like attention, non-planning, motor, and fine motor speed were not different between GAS+ and GAS- children. ADHD children had more infections, GAS, and antibodies than healthy children. GAS+ADHD children had more depression than GAS-ADHD children. ADHD children had more attention, impulsiveness, and fine motor problems.

Streptococcal infections, autoimmunity, and innate immune system in adult ADHD: A preliminary study

IntroductionHigh rate of streptococcus-like infections and related titers has been found in adult ADHD patients. No studies have expressively investigated innate immune system in ADHD patients.ObjectivesTo evaluate the relationship between streptococcal infections, autoimmunity and innate immune system in adult ADHD patients.MethodsThe study sample consisted of adult DSM-5 ADHD outpatients referring to the adult ADHD center of “San Luigi Gonzaga” University Hospital and non-clinical adult controls recruited among general population (screened using Adult ADHD Self-Report Scale - ASRS-v.1). All titers were determined in patients’ plasma by specific microwell ELISA kits, whereas genetic polymorphisms were determined by PCR methodology. We compared anti-streptolysin O (ASO), anti-deoxyribonuclease B (anti-DNase B), and anti-basal ganglia antibodies (ABGA) titers of patients with those of controls. Data about history of previous streptococcus/ streptococcus-like infections were collected by ad-hoc form. Furthermore, to investigate the susceptibility to Gram+-borne infections of adult ADHD patients, due to innate immune system impairment, we also evaluated the polymorphism of Toll-like receptors 2, 4, and 9.ResultsAlthough ADHD patients did not show higher rate of both previous infections (52.7% vs. 66.7%, p=.678) and ASO titers (18.2% vs. 0.0%, p=.577), they had really higher levels of anti-DNase B (85.5% vs. 16.7%, p=.001) and ABGA titers (78.2% vs. 33.3%, p=.036). Genetic analysis did not underline differences in polymorphism compared to general population (GENOME browser).ConclusionsThe high association between previous streptococcal infections, basal ganglia autoimmunity among ADHD patients was confirmed. TLR polymorphism does not seem to be involved in this type of vulnerability.DisclosureNo significant relationships.

Early childhood infections, antistreptococcal and basal ganglia antibodies in adult ADHD: a preliminary study

BackgroundTo explore the relationship between adult Attention Deficit/ Hyperactivity Disorder (ADHD), antistreptococcal titers, ABGA, and recurrent infections during early childhood.MethodChildhood history of recurrent infections and a blood sample were collected in a sample of DSM-IV adult outpatients with ADHD. The anti-streptolysin O (ASO), anti-deoxyribonuclease B (anti-DNase B), and anti-basal ganglia antibodies (ABGA) titers were determined in patient plasma by enzyme-linked immunosorbent assay (ELISA). Titers positivity was evaluated following manufacturer’s specifications. Absolute titers were also collected as continuous variables.ResultsFourteen out of 22 (63.6%) have had recurrent infections in childhood (i.e., seven, 31.8%, have had tonsillitis or adenoiditis and seven, 31.8%, have had any other infections). Eighteen patients (81.9%) were positive for anti-DNase B, five (22.7%) for ASO, and 4 (18.2%) were positive for both of them. Five participants (22.7%) were ABGA positive, whereas only two (9.1%) were positive for all three antibodies.Conclusionspatients with ADHD might be more prone to infections during childhood and subclinical streptococcal infections during adulthood. Moreover, they seem to have an increased risk for basal ganglia autoimmunity in adulthood. Both infections and the ensuing acquired autoimmunity could influence the neurodevelopmental process, by contributing, at least in part, to the ADHD pathogenesis.

Autoimmunity against a glycolytic enzyme as a possible cause for persistent symptoms in Lyme disease

Some patients with a history of Borrelia burgdorferi infection develop a chronic symptomatology characterized by cognitive deficits, fatigue, and pain, despite antibiotic treatment. The pathogenic mechanism that underlines this condition, referred to as post-treatment Lyme disease syndrome (PTLDS), is currently unknown. A debate exists about whether PTLDS is due to persistent infection or to post-infectious damages in the immune system and the nervous system. We present the case of a patient with evidence of exposure to Borrelia burgdorferi sl and a long history of debilitating fatigue, cognitive abnormalities and autonomic nervous system issues. The patient had a positive Western blot for anti-basal ganglia antibodies, and the autoantigen has been identified as γ enolase, the neuron-specific isoenzyme of the glycolytic enzyme enolase. Assuming Borrelia own surface exposed enolase as the source of this autoantibody, through a mechanism of molecular mimicry, and given the absence of sera reactivity to α enolase, a bioinformatical analysis was carried out to identify a possible cross-reactive conformational B cell epitope, shared by Borrelia enolase and γ enolase, but not by α enolase. Taken that evidence, we hypothesize that this autoantibody interferes with glycolysis in neuronal cells, as the physiological basis for chronic symptoms in at least some cases of PTLDS. Studies investigating on the anti-γ enolase and anti-Borrelia enolase antibodies in PTLDS are needed to confirm our hypotheses.

Anti-basal ganglia antibodies (ABGA) and excitatory neurotransmitters in obsessive-compulsive disorder (OCD)

IntroductionOCD is a complex disorder with multiple aetiological theories. Recent research points to role of autoimmunity as well as hyperactivity of glutaminergic pathways in aetiopathogenesis of the disorder. It is possible that autoimmune mechanisms may modulate excitatory neurotransmission resulting in OCD.Aims/objectivesThis study aimed to study the association between serum anti-basal ganglia autoantibodies (ABGA) and Glx (glutamate + glutamine) levels in caudate nucleus and anterior cingulate cortex as demonstrated by 1H-MRS (proton magnetic resonance spectroscopy).MethodsThirty psychotropic-naive OCD patients and an equal number of age, gender matched healthy controls were studied using 1H-MRS and levels of Glx were obtained. ABGA was measured using ELISA (enzyme linked immunosorbent assay) technique and categorised as present or absent in the serum.ResultsABGA was present in significantly higher proportion of patients as compared to controls (P < 0.05). Glx level was significantly higher (as measured by 1H-MRS) in patients with ABGA as compared to those without ABGA (P = 0.02). The study results did not differ based on age, gender, disease severity and illness duration.ConclusionsThe study demonstrates presence of ABGA in at least a subset of OCD population. The significant correlation between brain Glx levels and presence of ABGA provides a putative neurobiological framework for OCD. The strengths of the study include psychotropic-naive patients, blinded investigators and use of standardized instruments. The limitations include small sample size, use of Glx as proxy measure of glutamate and lack of other disorder controls. Similar studies on a larger sample are warranted for a better understanding.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Anti-Basal Ganglia Antibodies and Streptococcal Infection in ADHD

Objective: Group A Streptococcus has been associated with ADHD, tic disorders (TD), and obsessive–compulsive disorder (OCD) through anti-basal ganglia antibodies (ABGA). Method: We investigated the association between ABGA and streptococcal exposure with behavioral, motor, and cognitive measures in 38 children with ADHD not comorbid to OCD or TD (nc-ADHD) and in 38 healthy children. An additional group of 15 children with TD and/or OCD was examined. Results: ABGA titers were present in 3% of nc-ADHD patients and controls but in 27% of TD and/or OCD patients. Evidence of streptococcal exposure was similar between ADHD patients and controls living in the same urban area. Behavioral, motor, and cognitive measures were not associated with anti-streptococcal antibodies. Conclusion: ABGA do not distinguish nc-ADHD from controls. The differences in the frequency of streptococcal exposure in previous studies are determined by the dynamic nature of the infection rather than the behavioral phenotype of ADHD.

The PANDAS Controversy: Why (and How) Is It Still Unsettled?

Acute-onset OCD and/or tics in children, known by the term Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS), has been a focus of pediatric developmental and psychiatric research for nearly three decades. Studies have suggested that this condition results from molecular mimicry, in which anti-basal ganglia antibodies target brain proteins. While the pathogenesis of this condition is still widely debated, the clinical phenotype has shown consistent features and evidence that the dramatic symptoms cause substantial impairment in the child and in family functioning.

Anti-basal ganglia antibodies in primary obsessive-compulsive disorder: systematic review and meta-analysis.

Autoimmune-mediated basal ganglia dysfunction is implicated in the pathophysiology of neuropsychiatric disorders commonly manifesting with obsessive-compulsive features (e.g. Sydenham chorea). The relationship between autoimmunity and primary obsessive-compulsive disorder (OCD), however, is less clear. To pool data on serum and cerebrospinal fluid (CSF) anti-basal ganglia antibody (ABGA) positivity in primary OCD (without neurological or autoimmune comorbidity) relative to controls or neuropsychiatric disorders previously associated with increased odds of ABGA positivity. We performed electronic database and hand-searches for studies meeting pre-specified eligibility criteria from which we extracted data using a standardised form. We calculated pooled estimates of ABGA positivity using a random-effects model. Seven case-control studies totalling 844 participants met the eligibility criteria. Meta-analysis showed that a significantly greater proportion of those with primary OCD were ABGA seropositive compared with various controls (odds ratio (OR) = 4.97, 95% CI 2.88-8.55, P<0.00001). This effect was not associated with heterogeneity or publication bias, and remained significant after stratifying the analysis by age, gender, disease severity, illness duration, immunostaining methodology, study quality, publication type, kind of control group, and sample size. There were no significant differences in ABGA seropositivity for comparisons between primary OCD and Tourette syndrome, attention-deficit hyperactivity disorder or paediatric acute-onset neuropsychiatric syndrome. of one study testing CSF samples showed that a significantly greater proportion of participants with primary OCD were ABGA CSF-positive compared with healthy controls (OR = 5.60, 95% CI 1.04-30.20, P = 0.045). Odds of ABGA seropositivity are increased fivefold in primary OCD compared with controls, but are comparable to those associated with disorders previously associated with ABGA, providing circumstantial evidence of autoimmunity in a subset of those with primary OCD. Further experimental studies are needed to ascertain whether this relationship is causal.

Idiopathic progressive chorea: misnomer or still reality? A case with neuropathological disconfirmation

Dear Sir,Most of the rarer causes of chorea have been clarified in thelast decades [1], so that the classic term of ‘‘idiopathicchorea’’ has been critically put into question.A 50-year-old Caucasian woman was referred formarked and progressive generalized chorea. The onset wasabout 1 year before and a depressive syndrome was alsopresent. Past medical and family histories were unre-markable. Slight dysarthria and adiadochokinesia werenoted. Ocular movements were normal. Deep tendonreflexes were diffusely enhanced and plantar response wasin extension bilaterally. Routine serology, ceruloplasmin,tumour markers, HIV serology, onconeural- and auto-antibodies were negative. The anti-streptolysin-O titre wasborderline and careful examination of blood smears failedto demonstrate acanthocytes. A magnetic resonance and a99mTc-ECD SPECT brain scans were not significant. Theneuropsychological assessment evidenced only minorimpairment in selective attention and slight dysexecutivenotes. Genetic testing for Huntigton’s disease (HD, 17/25triplets), DRPLA (150/150), SCA17 (36/37), SCA1 (21/30), SCA2 (23/23), SCA3 (20/22), SCA6 (11/12), SCA7(9/11), and FXTAS (23/23) were negative. Progranulin andPRNP mutations or C9orf72 expansions were absent. Anti-basal ganglia antibodies (ABGA) testing (courtesy ofDr. Giovannoni and Martino, UCL, UK) resulted in a weakpositive binding to pyruvate kinase M1 (60 kDa), while nobinding was shown for both gamma-neuron specific eno-lase, and aldolase C.Since neuroleptics were ineffective, a trial with high-dose IV steroids was attempted, with no immediateimprovement (HD Functional Capacities score: 2/13, stageIV; Folstein Chorea Scale score: 37/57). Three monthslater, only minor changes were noted (HDFCS: 3/13, stageIV; FCS: 27/57). The patient further deteriorated present-ing diffuse spasticity and dystonia. Due to worseningdysphagia the patient was referred for PEG positioning, butshe anyhow died of aspiration pneumonia about 4 yearssince the onset of chorea.The neuropathological study was carried out on forma-lin-fixed sections stained with hematoxylin-eosin, cresylviolet for Nissl substance, Heidenhain-Woelcke for myelin,thioflavine S for amyloid, and silver salts for neurofibrillarychanges (Bodian’s method). Immunohistochemistry wasperformed with antibodies to beta-amyloid (4G8), alpha-synuclein (4D6), ubiquitin (polyclonal), phosphorylated tau(AT8), prion protein (3F4), GFAP (polyclonal), CD3/43,leucocytes common antigen CD45, and MBP (polyclonal).Histopathological examination revealed mild neuronal lossin the cerebral cortex and basal ganglia. Reactive astrogl-iosis and microglia activation were marked in the thalamus,caudate, putamen and substantia nigra (SN) and morepronounced in the brainstem and cerebellum. Slight peri-vascular lymphocytic infiltration was present in the hemi-spheric and cerebellar white matter as well as in thestriatum, thalamus and brainstem. Extracellular deposits orintracellular inclusions were absent but esinophilic, ubiq-uitin-positive inclusions suggestive of Marinesco bodieswere found only in the SN. No clear retrospective corre-lation with imaging data was possible.

Searching for the Immune Basis of Obsessive-Compulsive Disorder

The etiopathogenesis of obsessive-compulsive disorder (OCD) remains elusive. Clinical observation of the elevated frequency of obsessive-compulsive symptoms in patients with rheumatic fever, a post-streptococcal autoimmune disease, prompted the study of immune parameters in OCD. Anti-basal ganglia antibodies have been described in a subset of OCD patients. The assessment of circulating cytokines and immune cells confirmed unequivocal changes in at least some patients, although it is difficult to establish a particular immune profile in OCD. Several factors, including the use of psychotropic drugs and the presence of comorbid conditions, seem to influence these immune parameters.

Reopening the case for anti–basal ganglia antibodies (ABGAs): Identification of dopamine‐2 receptor antibodies associated with movement disorders

Reopening the case for anti–basal ganglia antibodies (ABGAs): Identification of dopamine‐2 receptor antibodies associated with movement disorders

Is there a Role for Immunological Mechanisms in Etiopathogenesis of Obsessive Compulsive Disorder?

Byline: Naren. Rao, M. Reddy, Janardhan. Reddy Obsessive compulsive disorder (OCD) is a common and debilitating neuropsychiatric disorder with a prevalence of approximately 2%. Though selective serotonin reuptake inhibitors (SSRI) are the mainstay of treatment, it is increasingly being recognized that serotonin abnormality may be the final common pathway and other mechanisms may also play important roles in the etiopathogenesis of OCD. Growing evidence from different lines of research in the last few years suggest possible role of immunologicalabnormalities in the pathogenesis of OCD. [sup][1] Influential studies from National Institute of Mental Health suggested higher prevalence of OCD and tics in patients with Sydenham's chorea and group A Streptococcal infection, implicating immunological mechanisms in a subtype of childhood OCD such as pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). [sup][2] Following this, studies examined other markers of immune abnormality and reported higher concentration of anti-basal ganglia antibodies [sup][3] and increased prevalence of B lymphocyte marker D8/17 [sup][4] in OCD patients than in healthy controls. Neuroimaging studies supported immune hypothesis in PANDAS, reporting decreased basal ganglia volume in children with streptococcus-associated OCD [sup][5] as well as correlation between basal ganglia volume and anti-basal ganglia antibody titers. [sup][5],[6] While these results suggest a role of immunological mechanisms in the pathogenesis of OCD, one needs to be careful before drawing final conclusion because these results are preliminary and not unequivocal. [sup][7] Recent research advances in psychoneuroimmunology have implicated cytokines as mediators between brain and immune system. In addition to their role in peripheral inflammation, cytokines affect central nervous system functioning by altering the neurotransmitter systems, importantly serotonin and glutamate. Pro- and anti-inflammatory cytokines have stimulatory and inhibitory effects, respectively, on the activity of enzyme indoleamine 2,3 dioxygenase (IDO). Stimulation of IDO converts tryprophan to kynurenine, decreasing tryptophan availability for serotonin production. Kynurenine is further converted to quinolinic acid, which is a glutamate (NMDA) receptor agonist. [sup][8] Hence, cytokines are proposed to play an important role in the pathogenesis of different neuropsychiatric disorders such as depression, post-traumatic stress disorder, schizophrenia, and dementia. In the last decade, studies have examined plasma cytokines in the pathogenesis of OCD, but have reported inconclusive results. On the other hand, few studies have reported elevated cytokine levels in OCD, with majority studies reporting absence of difference between patients and controls, as also corroborated by a recent meta-analysis. [sup][9] In summary, the existing data is inconsistent regarding the role of immunological mechanisms in the pathogenesis of OCD. The evidence does not conclusively suggest a role of immunological mechanisms in the pathogenesis for OCD in general, and, at the same time, does not rule out its possible role in a subgroup of OCD. Few possible reasons for the inconsistency are methodological. First, OCD is a heterogeneous disorder with varying age at onset, and pediatric OCD may be distinctly different from adult OCD. While pediatric OCD studies have implicated possible role for immunological mechanisms, results of studies in adult OCD are equivocal. In one study, age at onset had negative correlation with tumor necrosis factor-a levels, [sup][10] further supporting this view. Second confounding factor is the presence of comorbid diagnosis, importantly depression. Only few studies have examined OCD patients without comorbid diagnosis, and because immunological mechanisms are implicated in pathogenesis of other psychiatric disorders as well, it is difficult to delineate the effects specific to OCD. …

D01 Expanding the spectrum of chorea associated with immune-mediated diseases: two case reports

Background Wegener Granulomatosis (WG) and psoriasis are two rheumatologic diseases in which neurological involvement is quite rare. Case history A 72-years-old male, diagnosis of WG since 1999. Since 2003 he presented simple verbal tics, four limbs involuntary movements. The cognitive profile was in line with an amnestic mild cognitive impairment. Hyperkinetic syndrome improved with low dosages of Tetrabenazine. A 67-years-old woman presented with choreic movements mainly at the left limbs and painful swelling left wrist. Neuropsychological evaluation showed a mild frontal dysfunction. Within 4 months diagnosis of psoriasis was made. Methylprednisolone was given with improvement of chorea, instead tetrabenazine was stopped for parkinsonism. Genetic tests for HD, HDL2, SCA-17 and research for acanthocytis were negative. FDG-PET showed right caudo-putaminal hypermetabolism in the first patient and bilateral basal ganglia hypermetabolism in the second patient. Brain MRI didn9t show any significant alteration in both patients. CSF examination, iron and cupper sieric values were in the normal range. Sieric anti-basal ganglia antibodies (ABGA) showed auto-antigen of 45 kDa. Conclusions ABGA positivity has been described during autoimmune diseases such as Sydenham Chorea, ADEM and PANDAS‏ and post-mortem studies showed perivascular infiltration by lymphocytes in the basal ganglia. Striatal hypermetabolism on FDG-PET with chorea associated with SLE and primary antiphospholipid syndrome has been reported probably (1,2) due to autoantibodies vs basal ganglia neurons. The ABGA positivity does not imply a pathogenetic relationship, however the concomitant striatal hypermetabolism in our cases could extend the spectrum of chorea associated with autoimmune diseases.

Infusion of Sydenham's chorea antibodies in striatum with up-regulated dopaminergic receptors: A pilot study to investigate the potential of SC antibodies to increase dopaminergic activity

BackgroundSydenham's chorea (SC) is a neurological manifestation of rheumatic fever. Autoimmune mechanism of SC is supported by clinical improvement with immunomodulatory therapy; presence of circulating serum anti-basal ganglia antibodies; increase in Th2 group of cytokines in serum and CSF of patients. However, a role of the antibodies in the pathogenesis can only be established by their passive transfer. Chorea is a manifestation clearly related to increased dopaminergic (DA) activity. The purpose of this study was to investigate the potential of antibodies from patients with Sydenham's chorea to cause behavior alterations on rats with unilateral post-synaptic dopamine receptor up-regulation. MethodsRats previously submitted to 6-hydroxidopamine (6-OH-DA) unilateral lesion of substantia nigra pars compacta (SNc) and tested with apomorphine to ensure DA receptors up regulation, received intrastriatal infusion of antibodies from SC patients (n=4) or healthy controls (n=3) during 48h. 24h post infusion initiation (24PI) and 48h post infusion initiation (48PI), we registered the occurrence of spontaneous contra lateral rotations (CLR). FindingsSC group exhibited significantly higher number of CLR than control group at 24PI (p=0.049) and 48PI (p=0.048). ConclusionThe limited sample of the present study restricts us to affirm that SC is really an immune-mediated condition. However the significant result of this pilot study points to preliminary evidence that SC antibodies may affect DA activity in rats with up-regulated striatal DA receptors.

Prevalence of anti-basal ganglia antibodies in adult obsessive–compulsive disorder: cross-sectional study

Symptoms of obsessive-compulsive disorder (OCD) have been described in neuropsychiatric syndromes associated with streptococcal infections. It is proposed that antibodies raised against streptococcal proteins cross-react with neuronal proteins (antigens) in the brain, particularly in the basal ganglia, which is a brain region implicated in OCD pathogenesis. To test the hypothesis that post-streptococcal autoimmunity, directed against neuronal antigens, may contribute to the pathogenesis of OCD in adults. Ninety-six participants with OCD were tested for the presence of anti-streptolysin-O titres (ASOT) and the presence of anti-basal ganglia antibodies (ABGA) in a cross-sectional study. The ABGA were tested for with western blots using three recombinant antigens; aldolase C, enolase and pyruvate kinase. The findings were compared with those in a control group of individuals with depression (n = 33) and schizophrenia (n = 17). Positivity for ABGA was observed in 19/96 (19.8%) participants with OCD compared with 2/50 (4%) of controls (Fisher's exact test P = 0.012). The majority of positive OCD sera (13/19) had antibodies against the enolase antigen. No clinical variables were associated with ABGA positivity. Positivity for ASOT was not associated with ABGA positivity nor found at an increased incidence in participants with OCD compared with controls. These findings support the hypothesis that central nervous system autoimmunity may have an aetiological role in some adults with OCD. Further study is required to examine whether the antibodies concerned are pathogenic and whether exposure to streptococcal infection in vulnerable individuals is a risk factor for the development of OCD.

Some Adults with OCD Have Anti–Basal Ganglia Antibodies

Anti–basal ganglia antibodies (ABGAs) have been found in patients with Sydenham chorea, which is a sequel of streptococcal infection (strep) and has a

110 Narcolepsy: Is it a sequelae of auto-immune encephalitis/encephalitis lethargica?

IntroductionNarcolepsy often begins in childhood (30% of cases) but only around 4% are diagnosed before age 15. It is usually a slowly progressive disease, with mild symptoms. We report a...

MAb10F5 is an Anti-Phospholipid Antibody that Binds in the Basal Ganglia in Vivo

IgG2b antibodies are hypothesized to have more anti-phospholipid activity and therefore more likely to enter tissues from the bloodstream. The group A streptococcal conservative M protein sequence when injected into mice generates a promiscuous IgG2b antibody referred to as mAb10F5. Streptococcal antibodies are involved in latent streptococcal disorders including disorders which require movement of antibody into the brain (basal ganglia; caudate/putamen or CPu). Previously, our laboratory demonstrated the binding of streptococcal mAb10F5 with CPu and with liposomes. To determine if mAb10F5 binding to basal ganglia would occur in vivo and if binding with lipids is due to virulence of the antibody or antibody subtype, rats were injected with either control IgG2 antibodies or mAb10F5 and euthanized after 24, 48, or 72 hours. Brains were harvested and immunofluorescence was used to analyze brain slices. Control IgG2 injected rats showed significantly less fluorescence in the CPu than mAb10F5 injected rats at each of the time points (p<0.05). These findings reaffirmed mAb10F5 as an anti-basal ganglia antibody. Fluorescent clouds were visible in slices of brain acquired from mAb10F5 injected rats suggesting entry of the antibody from the bloodstream but not in IgG2 injected controls. To evaluate an anti-phosphopholipid mode of antibody entry, mAb10F5 was examined for anti-phospholipid activity using ELISA. MAb10F5 generated significantly different curves for phosphotidylserine (PS) as compared to phosphotidylinositol (PI) (p<0.05). Though mAb10F5 displayed greater affinity to lipids (PI, PS and cardiolipin were examined) in general when compared to IgG2 controls, mAb10F5 was not significantly different from IgG2b when variation between ELISAs was taken into account. Our findings support mAb10F5 as an anti-basal ganglia antibody in vivo and anti-phospholipid antibody due in part to its own virulence and in part to being an IgG2b subtype.

P-1029 - Anti basal ganglia autoimmunity: OCD and movement disorder associated with anti neuron specficic enolase and anti pyruvate kynase autoantibodies

We describe a case of OCD and movement disorders associated with anti basal ganglia antibodies. A 17 year old patient was referred to our unit in February 2010 because of movement disorder. He denied personal or family history of psychiatric disorders and substance abuse other that occasional cannabis use. His symptoms had began 6 months earlier when he started presenting intrusive thoughts associated with various compulsions such as complex arm and leg movements and bizarre postures: he was treated with Olanzapine and Sertraline which lead to partial improvement of symptoms but he self-discontinuated the medication in january 2010. Upon admittance in february 2010 the patient showed obsessive thoughts associated with bizarre postures and upper limb complex movements. He was treated with 100 mg of Clomipramine which lead to partial regression of symptoms. Autoimmunity screening was performed revealing anti neuron specific enolase and anti pyruvate kynase antibodies. The patient was treated with Desametasone which did not lead to any improvement. Anti neuron specific enolase and anti pyruvate kynase antibodies are directed against antigens specifically expressed in the basal ganglia. According to literature data these autoantibodies can be associated with movement disorders and OCD and we hypothesize that our patient's symtptoms were caused by autoimmunity. Although cortison was not successfull, recents reports in scientific literature have shown that other non psychopharmacological treatment, such as plasmapheresis, or IV immunoglobulins could be effective in similar patients: we are considering this as our next treatment option.

The relationship between group A streptococcal infections and Tourette syndrome: a study on a large service-based cohort

To evaluate the relationship between diagnosis and clinical course of Tourette syndrome and group A Streptococcus (GAS). GAS infections, anti-streptococcal, and anti-basal ganglia antibodies (ABGA) were compared between 168 patients (136 males, 32 females) with Tourette syndrome; (median [range] age [25th-75th centile] 10y [8-11y]); median Tourette syndrome duration (25th-75th centile), 3y (1y 3mo-5y 9mo) and a comparison group of 177 patients (117 males, 60 females) with epileptic or sleep disorders median age [25th-75th centile], 10y [8y-1y 6mo]). One hundred and forty-four patients with Tourette syndrome were followed up at 3-month intervals; exacerbations of tics, obsessive-compulsive symptoms, and other psychiatric comorbidities were defined by a bootstrap procedure. The effect of new GAS infections and identification of new ABGA upon risk of exacerbation was assessed using logistic regression analysis. Cross-sectionally, patients with Tourette syndrome exhibited a higher frequency of GAS infection (8% vs 2%; p=0.009), higher anti-streptolysin O (ASO) titres (246 [108-432] vs 125 [53-269]; p<0.001), and higher ABGA frequency (25% vs 8%; p<0.001) than the comparison group. On prospective analysis, ASO titres were persistently elevated in 57% of patients with Tourette syndrome; however, new infections or newly identified ABGA did not predict clinical exacerbations (all p>0.05). Patients with Tourette syndrome might be more prone to GAS infections and develop stronger antibody responses to GAS, probably as a result of underlying immune dysregulation. New GAS infections are unlikely to exert, years after their onset, a major effect upon the severity of neuropsychiatric symptoms.