Autoimmune-- Pandas/TS/Tic-disorder

[myrose]

It seems that all is leaning towards Pandas being an autoimmune....does everyone agree with this?

 

So TS/Tics are not considered to be autoimmune but possibly a inherited gene???

 

 

I would love all your comments.

 

 

I guess I am wondering if IVIG would also treat tics/ or TS???

[Caryn]

Myrose,

I found an interesting thesis from the Netherlands on the subject. I will post the conclusion and a link. (It is long, 171 pages, but all available online for free if you have the time to read.)

http://dissertations.ub.rug.nl/FILES/facul...stra/thesis.pdf

To conclude, though several studies suggest the presence of autoantibodies reacting with brain tissue in patients with OCD and/or tic disorders, some of these raise concerns regarding methodology. Moreover, the presence of autoantibodies in the serum of patients with tic disorders does not necessarily point to an autoimmune basis of tic disorder. Autoantibodies are also found when tissue damage is caused by trauma or infection. In other words, autoantibodies can result from, rather, than be the cause of tissue damage, as has been reviewed elsewhere.41 One recent study, however, elegantly suggested a pathogenic role for antineuronal antibodies for tic disorders. Through the transfer of antineuronal antibodies of children with TS to the striatum of rats, stereotypic movements and utterances could be induced in these animals. Much remains to be investigated in this area, eg, how autoantibodies present in sera are able to cross the blood-brain barrier, or whether IgG production takes place inside the central nervous system. Simply measuring albumin and total IgG in serum as well as in cerebrospinal fluid would give valuable information about IgG production in the central nervous system and about the functional integrity of the blood-brain barrier. Recently, basic principles of these measurements have been adequately reviewed.43 Theoretically, in this respect, it would be also of interest, to compare antineuronal antibodies instead of total IgG in both serum and cerobrospinal fluid. Contrary to total IgG, however, we lack accurate quantitative methods of measuring levels of antineuronal antibodies, as has been outlined in the previous sections.

Also, the way in which antibodies against neuronal antigens might induce tics and associated features is unknown. No evidence of antibody-associated inflammation or indications of autoantibody binding to functional cell-surface receptors in central nervous tissue have been collected in the field of tic and related disorders. An animal model as described above,42 or careful postmortem neuropathological examinations may be fruitful future approaches in this respect.

and on pg. 95 (Chapter 8) he writes about the common cold and exasperations of tics 4 wks later:

Conclusion: While it remains to be proven whether or not streptococcal infections are associated with exacerbations in tic severity, this study points to a hitherto unknown association of common viral infections with exacerbations in tic severity in children, which may support the involvement of immune dysregulation in tic disorders.

And more,

Though the precise mechanism at a molecular level is unknown, a growing number of studies suggest the involvement of autoimmunity in the pathogenesis of tic disorders.1 A common feature of autoimmune disorders in general is their relapsing course over time. Infections have been suggested to induce or reinforce autoimmune reactions in genetically predisposed individuals, and may, thus, be associated with exacerbations and remissions in autoimmune conditions.

A pattern of fluctuations in symptom severity is also common in tic disorders. Some authors have suggested an association between infections with group A betahemolytic streptococci and changes in tic severity in at least a subgroup of patients. This possible relationship has been exclusively based on cross-sectional data and some case studies, however. In the present prospective longitudinal study, we aimed to examine the possible temporal relationship between symptom exacerbations and preceding infections in an unselected cohort of pediatric and adult patients with a tic disorder.

Conclusion:

Although the first notion of a possible link between infection and tic disorders dates back to 1929, this is the first study that examined the association between

exacerbations in tic severity and preceding infections in a prospective longitudinal design. In the pediatric patients, we found a strong association between self-reports of a common cold and a subsequent exacerbation in tic severity 4 weeks later. It is improbable that this is due to a nonspecific stress reaction, since we did not find an association with tic exacerbations in other weeks, including the week in which the common cold was newly reported. The usual duration of cold symptoms in children is 10 to 14 days, thus, the cold has already entirely disappeared by the time of the tic exacerbation, 4 weeks later. In contrast, we did not encounter this association in the adult patients. Only a trend regarding the occurrence of tic exacerbations 3 weeks after the cold may be noticeable in adults. Apparently, children and adults differ with regard to the impact of infections on changes in tic severity. While differences between children and adults are well-known with regard to both the 100 Chapter 8 Common cold and exacerbations immunological response to infections and the maturity of the nervous system, at

present, we do not have a plausible explanation for the different impact of upper respiratory infections on children and adults with a tic disorder. Future studies

should focus on the immunological pathways that may be involved. Also, speculations about why the time frame between the upper respiratory infection and

the subsequent exacerbation in tic severity appears to be 4 weeks, will have to await such studies. Currently, we know of one additional study16 that pointed to the

relevance of common colds in obsessive-compulsive and tic disorders. In that study, the presence of common cold at the time of onset of obsessive-compulsive disorder and tic symptoms appeared to be associated with sudden, rather than insidious onset of symptoms. Prior studies pointed to a possible association between tic disorders and streptococcal infections, as was suggested by increased serum levels of antistreptococcal antibodies in unselected patients with a tic disorder. Though that approach bears the risk of circular reasoning, other authors preferred to preselect patients based on working criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Indeed, a number of prospectively identified PANDAS cases have recently been presented. Thus, there is some indication that streptococcal infections may be associated with tics. We intended to address this issue in the present study, but identified only one streptococcal infection in the pediatric cohort versus none in the adult patient group over a period of 16 weeks. This frequency of streptococcal infections in our patient groups is in accordance with a reported annual incidence of group A streptococcal throat infections of 36 per 1000 in the general population. In contrast, a previous study prospectively identified 35 streptococcal infections, albeit with a somewhat less stringent definition, during 8 months in 37 children fulfilling PANDAS criteria, despite use of penicillin during 4 of these 8 months. That finding suggests the possibility that children with tics and related disorders would be more susceptible to streptococcal infections. Also, the studies of Muller and Cardona would be in accordance with a possibly more frequent incidence of streptococcal infections in tic disorder patients. We were not able to address the issue whether or not streptococcal infections are associated with subsequent exacerbations in tic severity. However, the data of the present study do not appear to support a more frequent occurrence of streptococcal infections in tic disorder patients, compared to the general population. Thus, given the relatively low incidence of streptococcal infections, their role in clinical practice appears to be rather limited. In contrast, common colds are fairly frequent, with an annual incidence of around four colds per year in teenagers and adults, which center around the winter season in temperate climates. Thus, the present study’s reported frequency of slightly more than two colds per individual during the 24 weeks’ study period in the fall and winter period, fits well to established epidemiological figures. Common cold is almost exclusively a viral disease. Viral infections are well known to trigger autoimmune conditions, though the precise mechanism of induction of autoimmunity by viral infections is largely unknown. Since common colds can be

caused by a plethora of viral species, future studies should try to identify which viruses may be associated with tic exacerbations in children, and how these may

influence antineuronal antibody levels. Also, it would be of interest to prospectively study the role of infections regarding the onset of tic disorders, eg in young children with one or both parents and/or siblings affected by tics. In the present study, we exclusively relied on subjective self-questionnaires for both detecting tic exacerbations as well as common colds. Thus, future studies should try to objectively determine exacerbations in tic severity, using established

rating instruments,3 preferably with at least weekly assessments of tic severity. In addition, such studies may want to objectively document symptoms of common

cold. However, the excellent response rates in our study over a period of 24 weeks surely is an indicator of the high motivation of participants, and thus, of the

reliability of the present data. In conclusion, the present finding that common cold appears to be associated with children’s exacerbations in tic severity 4 weeks later, adds to the growing literature that indicates the possible involvement of the immune system in tic disorders. In addition, this finding underlines the unique possibilities of tic disorders to study the complex interplay between immune factors, brain functioning and behavior.

Sorry so long....

Chapter 10 is about IVIG. "Lack of effect of intravenous immunoglobulins on tics: a double-blind placebo controlled study" pg 119 for anyone interested.

Only a single placebo-controlled study is available with regard to immune-based treatments. That study pointed to the effectiveness of both plasma exchange and IVIG in pediatric tic and obsessive-compulsive disorder patients who all met PANDAS criteria,8 compared to a placebo condition. Interestingly, a single course of plasma exchange or IVIG resulted in positive effects that were still present at 1 year after treatment. Treatment with IVIG resulted in significant improvements in obsessive-compulsive symptoms, anxiety, and depression. However, the IVIG group did not show significant improvement in tic severity. Since the study of Perlmutter et al. included two different disorders, that is, obsessive-compulsive disorder (OCD) and/or tic disorders, the number of patients with tics in that study was rather low (eight children with tics in the placebo group versus four in the IVIG group). In addition, given the PANDAS criteria that subjects had to meet, which require evidence of an association between streptococcal infection and onset or exacerbation of signs and symptoms, the patients who were enrolled in the study may well not be representative of tic disorder patients in general. In other words, whether IVIG benefits tic severity in unselected patients with a tic disorder has not been addressed. This is an important issue, given the possible involvement of immune factors across tic disorder patients who were not specifically preselected using PANDAS. Meanwhile, the imposing results of the single placebocontrolled study, as well as the published highly successful case reports,13-15

information which is readily accessible to a lay public via the internet, has occasionally led to considerable pressure inflicted on clinicians by tic disorder patients or their parents to apply one of the immunomodulatory treatment options. Lack of effect of IVIG Also, many clinicians themselves wonder if they should refer their patients with tic or related disorders to such treatment modalities, especially given the paucity of currently available treatment possibilities, which consist largely of the use of antipsychotic agents, that are purely symptomatic and may have troublesome sideeffects. This led us to conduct the present double-blind study in which we compared the therapeutic effect of a single course of IVIG with a placebo condition in a group of unselected patients with a chronic tic disorder. We used changes in tic severity as the primary endpoint of the study. In addition, we assessed changes in obsessive-compulsive symptoms.

More available online......

[Chemar]

as my son has Crohn's disease(which is autoimmune) and Tourette Syndrome (genetically inherited from his dad/grandfather etc) I must say that before the crohn's manifest, I did not see what I have come to recognize as autoimmune reactions related to his TS...in fact quite the opposite.

 

I think one also needs to be very careful to blanket all tic disorders as they have many different origins and solutions. Tourette Syndrome is known to involve malfunction at the dopamine level. Not all tic disorders are dopamine related from my understanding.

[Caryn]

I think one also needs to be very careful to blanket all tic disorders as they have many different origins and solutions. Tourette Syndrome is known to involve malfunction at the dopamine level. Not all tic disorders are dopamine related from my understanding.

Yes, Cheri, Dr. Hoekstra says as much in his thesis. I think it is a must read.

[myrose]

WHEW!!! Can't comment yet...not done reading it! I think I am getting over my head here in this though.....I will finish it later.

Very interesting Caryn

[guy123]

Great, now I have another 171 pages to read... lol.

 

Chemar, can you give examples of non-dopamine related tic conditions?

 

Thanks.