Lactobacillus plantarum PS128 ameliorates 2,5-Dimethoxy-4-iodoamphetamine-induced tic-like behaviors via its influences on the microbiota-gut-brain-axis.

We previously reported a novel psychobiotic strain of Lactobacillus plantarum PS128 (PS128) which could ameliorate anxiety-like& depression-like behaviors and modulate cerebral dopamine (DA) and serotonin (5-HT) in mice. Here, we examine the possibility of using PS128 administration to improve tic-like behaviors by using a 5-HT2A and 5-HT2C receptor agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI). PS128 was orally administered to male Wistar rat for 2 weeks before two daily DOI injections. We recorded the behaviors immediately after the second DOI injection and compared the results with control and haloperidol treatment groups. PS128 significantly reduced tic-like behaviors and pre-pulse inhibition deficit in a threshold-dose of 109 CFU per day. Brain tissue analysis showed that DOI induced abnormal DA efflux in the striatum and prefrontal cortex, while PS128 ingestion improved DA metabolism and increased norepinephrine (NE) levels in these two regions. In addition, PS128 ingestion increased DA transporter and ß-arrestin expressions and decreased DOI-induced phosphorylation of DA and cAMP regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) at Thr34 and extracellular regulated protein kinases (ERK). PS128 ingestion also modulated peripheral 5-HT levels and shaped the cecal microbiota composition, which helps to alleviate DOI-induced dysbiosis. These results suggested that PS128 ameliorated DOI-induced tic-like hyper-active behaviors via stabilizing cerebral dopaminergic pathways through its modulation of host's microbiota-gut-brain axis. Thus, we believe there are potentials for utilizing psychobiotics to improve syndromes caused by DA dysregulation in DA-related neurological disorders and movement disorders such as Tourette syndrome.

[Transmission and circulation of tick borne pathogens (TBE and Lyme borreliosis) and the role of changing environment]. / Transmisja i krazenie patogenów odkleszczowych (kzm i boreliozy) i rola zmieniajacego sie srodowiska.

Ixodes ricinus is regarded as a species with great medical and veterinary meaning. Transmission of tick borne pathogens in mammals depends not only on systemic infection. Transmission of B. burgdorferi and tick-borne encephalitis virus in an infected organism differs, because of different location in tick, the differences in dissemination of the virus and bacteria (own motility) as well as mechanisms supporting bacterial infection. The mechanisms governing the transmission of these pathogens in nature have epidemiological importance and are essential in understanding the pathogenesis of diseases. The increase in the incidence of tick-borne encephalitis in recent years, is a marker of tick borne diseases. In the 90s, the number of cases among humans in many European countries remains at a higher level compared to the eighties. Similar observations consider to Lyme borreliosis. Natural environmental changes, mainly related to climate, as well as regional and local changes in distribution of the small rodents species, wild animals, anthropogenic factors (reforestation, drainage of swamps, increasing the reservoir of animals), and social change (increased human activities in forests, vaccinations) may have a significant impact on rates of tick-borne diseases.

Streptococcal infection and exacerbations of childhood tics and obsessive-compulsive symptoms: a prospective blinded cohort study.

OBJECTIVE: If pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections is a unique clinical entity, we hypothesized that children meeting diagnostic criteria would have more clinical exacerbations temporally linked to bona fide group A beta-hemolytic streptococcus infection than matched control subjects (chronic tic and/or obsessive-compulsive disorder with no known temporal relationship to group A beta-hemolytic streptococcus infection). PATIENTS AND METHODS: Subjects included 40 matched pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections case-control pairs who were prospectively evaluated with intensive laboratory testing for group A beta-hemolytic streptococcus and clinical measures for an average of 2 years. Additional testing occurred at the time of any clinical exacerbations or illness. Laboratory personnel were blinded to case or control status and clinical (exacerbation or not) condition. Clinical raters were blinded to the results of laboratory tests. RESULTS: The cases had a higher clinical exacerbation rate and a higher bona fide group A beta-hemolytic streptococcus infection rate than the control group. Only 5 of 64 exacerbations were temporally associated (within 4 weeks) with a group A beta-hemolytic streptococcus infection, and all occurred in cases. The number (5.0) was significantly higher than the number that would be expected by chance alone (1.6). Yet, >/=75% of the clinical exacerbations in cases had no observable temporal relationship to group A beta-hemolytic streptococcus infection. CONCLUSIONS: Patients who fit published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections seem to represent a subgroup of those with chronic tic disorders and obsessive-compulsive disorder who may be vulnerable to group A beta-hemolytic streptococcus infection as a precipitant of neuropsychiatric symptom exacerbations. Group A beta-hemolytic streptococcus infection is not the only or even the most common antecedent event associated with exacerbations for these patients. Additional intensive studies are needed to determine whether there is clinical or scientific evidence to support separating out subgroups of tic disorder and/or obsessive-compulsive disorder patients based on specific symptom precipitants.

PANDAS: uma nova doença? / PANDAS: a new disease?

OBJETIVO: Apresentar as bases diagnósticas e analisar as evidências que têm sido apontadas para a etiopatogenia, tratamento e profilaxia de PANDAS. FONTES DOS DADOS: Revisão de literatura científica através do MEDLINE no período de 1989 a 2006. SíNTESE DOS DADOS: Os critérios diagnósticos para PANDAS foram estabelecidos há quase 10 anos, mas ainda há muita controvérsia sobre a real existência desta nova doença pediátrica. A escolha deste nome para uma nova doença, supostamente de origem pós-estreptocócica, baseia-se no acrônimo de P (pediátrico, porque ocorre em crianças), A (auto-imune), N (neuropsiquiátrico), D (doença), A (associada) e S (Streptococcus). Os tiques e os sintomas obsessivo-compulsivos são as principais manifestações clínicas da doença e surgem após infecções estreptocócicas, provavelmente por mecanismos auto-imunes. Apesar de estes sintomas neuropsiquiátricos serem comuns na coréia reumática, também de etiologia pós-estreptocócica, em PANDAS faltam os movimentos clássicos da coréia e as outras manifestações de febre reumática. As possibilidades de terapia antimicrobiana e imunológica estão sendo pesquisadas e demonstram viabilidade de uso em alguns casos. CONCLUSÕES: Pesquisas ainda são necessárias para responder à pergunta-título. Enquanto isso não ocorre, a identificação de casos de tiques e transtorno obsessivo-compulsivo em crianças deve considerar a possibilidade de PANDAS, buscando a evidência de infecção estreptocócica precedendo os episódios.

OBJECTIVE: To establish the diagnostic criteria for PANDAS and to analyze the existing evidence regarding its etiopathogenesis, treatment and prophylaxis. SOURCES: Review of the scientific literature through a MEDLINE search carried out between 1989 and 2006. SUMMARY OF THE FINDINGS: The diagnostic criteria for PANDAS were established nearly 10 years ago, but a lot of controversy still exists over the actual existence of this new pediatric disease. The name of this new disease, supposedly of poststreptococcal etiology, derives from an acronym that stands for pediatric autoimmune neuropsychiatric disease associated with streptococcal infection. Tics and obsessive-compulsive symptoms are the major clinical signs of the disease, which develop after streptococcal infections, probably through autoimmune mechanisms. Even though these neuropsychiatric symptoms are common in rheumatic chorea, whose etiology is also poststreptococcal, the classic choreiform movements and other symptoms of rheumatic fevers are absent in PANDAS. The use of antimicrobial and immunologic therapy has been investigated and considered feasible in some cases. CONCLUSIONS: Further research is still necessary in order to answer the question posed in the title of this article. In the meantime, the identification of tic disorders and obsessive-compulsive disorders in children should include the possibility of PANDAS, seeking to provide evidence of previous streptococcal infection.

PANDAS: a new disease?

OBJECTIVE: To establish the diagnostic criteria for PANDAS and to analyze the existing evidence regarding its etiopathogenesis, treatment and prophylaxis. SOURCES: Review of the scientific literature through a MEDLINE search carried out between 1989 and 2006. SUMMARY OF THE FINDINGS: The diagnostic criteria for PANDAS were established nearly 10 years ago, but a lot of controversy still exists over the actual existence of this new pediatric disease. The name of this new disease, supposedly of poststreptococcal etiology, derives from an acronym that stands for pediatric autoimmune neuropsychiatric disease associated with streptococcal infection. Tics and obsessive-compulsive symptoms are the major clinical signs of the disease, which develop after streptococcal infections, probably through autoimmune mechanisms. Even though these neuropsychiatric symptoms are common in rheumatic chorea, whose etiology is also poststreptococcal, the classic choreiform movements and other symptoms of rheumatic fevers are absent in PANDAS. The use of antimicrobial and immunologic therapy has been investigated and considered feasible in some cases. CONCLUSIONS: Further research is still necessary in order to answer the question posed in the title of this article. In the meantime, the identification of tic disorders and obsessive-compulsive disorders in children should include the possibility of PANDAS, seeking to provide evidence of previous streptococcal infection.

Anti-basal ganglia antibodies in PANDAS.

An autoimmune-mediated mechanism involving molecular mimicry has been proposed for a variety of pediatric movement disorders that occur after a streptococcal infection. In this study, anti-basal ganglia antibodies (ABGA) were measured in 15 children with the diagnosis of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and compared with those in 15 controls. ELISA and Western immunoblotting (WB) methods were used to detect ABGA against supernatant (S1), pellet (P2), and synaptosomal preparations from adult postmortem caudate, putamen, and globus pallidus. ELISA optical density values did not differ between PANDAS patients and controls across all preparations. Immunoblotting identified multiple bands in all subjects with no differences in the number of bands or their total density. Discriminant analysis, used to assess mean binding patterns, showed that PANDAS patients differed from controls only for the caudate S1 fraction (Wilks' lambda = 0.0236, P < 0.0002), with PANDAS-primarily tic subjects providing the greatest discrimination. Among the epitopes contributing to differences between PANDAS and control in the caudate S1 fraction, mean binding to the epitope at 183 kDa was the most different between groups. In conclusion, ELISA measurements do not differentiate between PANDAS and controls, suggesting a lack of major antibody changes in this disorder. Further immunoblot analyses using a caudate supernatant fraction are required to completely exclude the possibility of minor antibody repertoire differences in PANDAS subjects, especially in those who primarily have tics.

Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics.

BACKGROUND: A subgroup of children with obsessive-compulsive and tic disorders are proposed to have an infectious trigger. The purpose of this study was to investigate the relationship between group A streptococcal titers and symptom fluctuations in children with a clinical course resembling that described for pediatric autoimmune neuropsychiatric disorders associated with streptococcus. METHODS: Twenty-five children with obsessive-compulsive disorder and/or tic disorder were evaluated for neuropsychiatric severity and group A streptococcal antibody titers (streptolysin O, deoxyribonuclease B, and carbohydrate A) at 6-week intervals for > or = six consecutive evaluations (total visits=277). RESULTS: Children with large symptom fluctuations (n=15) were compared with children without dramatic fluctuations (n=10). Co-movements of obsessive-compulsive/tic severity and group A streptococcal antibodies were assessed. In subjects with large symptom changes, positive correlations were found between streptococcal titers and obsessive-compulsive severity rating changes (p=.0130). These subjects were also more likely to have elevated group A streptococcal titers during the majority of observations (p=.001). Tic symptom exacerbations occurred more often in the fall/winter months than spring/summer months (p=.03). CONCLUSIONS: Patients with marked obsessive-compulsive/tic symptom changes may be characterized by streptococcal titer elevations and exhibit evidence of seasonal tic exacerbations.