Hoekstra's and Zykov's studies of IVIG in patients with tics? +/- autoimmune markers?

[wisdom_seeker]

Does anyone have access to these studies? I'm posting it in the PANDAS forum because you -- like I -- are the folks with strong motivation to find and analyze all IVIG studies related to PANDAS.

 

Hoeekstra's is presented as a negative study of IVIG for to treat Tourette's. If it's a sophisticated review, such as the Eur Child Adolescent Psych guidelines on treatment of Tourette's, they describe it a study of lack of benefit in unselected patients with a tic disorder. But it was only 30 patients, I believe almost all adults, so likely quite chronic, randomized to IVIG vs. Placebo.

 

In contrast, I find exciting Zykov et. al.'s series of IVIG in pediatric Tourette's patients selected for elevated ganglia autoimmune markers, for whom IVIG seems to have had impressive benefit:

Neurosci Behav Physiol. 2009 Sep;39(7):635-8.

Neuroimmune aspects of the pathogenesis of Tourette's syndrome and experience in the use of immunoglobulins in children.

Zykov VP1, Shcherbina AY, Novikova EB, Shvabrina TV.

Abstract

A total of 60 patients aged 6-16 years with tics and Tourette's syndrome were studied. Antibodies to caudate nucleus proteins were assayed by western blot hybridization. Ten patients with Tourette's syndrome were found to have antibodies to caudate nucleus protein.
Seven patients with neuroleptic-resistant types of Tourette's syndrome received single transfusions of immunoglobulin preparations, which produced regression of vocal and motor hyperkinesias and improvement in behavior (remission for more than six months).
The observation of antibodies to caudate nucleus proteins and the positive effects seen on administration of immunoglobulins to patients with Tourette's syndrome support previous data on the possibility of using immunoglobulin therapy in the treatment of tic-type hyperkinesias and provide evidence of the involvement of autoimmune mechanisms inducing damage to the dopaminergic system of the striatum.

 

In Zykov's study, I'm delighted to see a large starting group of patients, so we have more trust in the 1/6 ratio of autoimmune. Still, I need specifics on the distribution of outcomes -- did each of the 7 remit completely, and how sustained were the benefits for each? I'd like to know which autoantibody they tested too :-). T'would be nice if they also compared the outcomes for the untreated patients, showing that the IVIG benefit was strikingly different.

 

As far as Hoekstra's trial (below), it had only 30 patients, randomized 15 to IVIG and 15 to placebo. Not bad, but Zykov found autoimmune basis in only 1/6 of a group of 60. 1/6 would mean only ~5 autoimmune based ... easily as few as 2, perhaps up to 7, randomly assigned to treatment or placebo. No wonder there was no response on tics. But what about the OCD and global improvement? I'm puzzled by the "Then" in Hoekstra's abstract (see the purple "Then" below). My read is that even in this population, not selected by CAMKII levels or other measures of autoantibodies, IVIG had a clinicially important benefit their overall wellbeing score lasting to the end of the study, and of benefit on OCD, but with subclinical OCD the study was way underpowered for that. But that's just an abstract.

 

I'd love to see both full studies, especially any graphs of tics, OCD, wellbeing over time. Ideally graphs of individual patients' scores, so that we could see if Hoekstra perhaps had a stand-out subpopulation of 2-3 whom it was beneficial.

 

J Clin Psychiatry. 2004 Apr;65(4):537-42.

Lack of effect of intravenous immunoglobulins on tics: a double-blind placebo-controlled study.

Hoekstra PJ1, Minderaa RB, Kallenberg CG.

BACKGROUND:

Case studies and a placebo-controlled study previously suggested the effectiveness of immunomodulatory therapy in patients with tic or related disorders whose symptoms show a relationship with streptococcal infections. No data are available on the effectiveness of intravenous immunoglobulins (IVIG) on tic severity in unselected tic disorder patients.

METHOD:

Thirty patients with a DSM-IV tic disorder were randomly assigned to IVIG (1 g/kg on 2 consecutive days; mean age = 28.71 years; range, 14-53 years) or placebo (mean age = 30.73 years; range, 14-63 years). Symptoms were rated with the Yale Global Tic Severity Scale, the Yale-Brown Obsessive Compulsive Scale, and the Clinical Global Impressions scale of symptom change with regard to tic severity. These were used at baseline and on weeks 2, 4, 6, 10, and 14 posttreatment, after which blinding was broken. The study was conducted from March through August 2002.

RESULTS:

We observed no significant differences between both treatment groups regarding posttreatment changes in tic severity. Severity of obsessions and compulsions, which was in the subclinical range, decreased significantly in the IVIG group compared with the placebo group at week 6 (p =.02). Then, there was a 32.3% improvement in the IVIG group compared with baseline. Though this improvement was maintained over the following 8 weeks, no statistically significant differences between the IVIG and the placebo group with regard to improvements in obsessions and compulsions were detected at subsequent assessments. IVIG treatment was associated with significantly more side effects than placebo, most notably headache.

CONCLUSION:

Based on the present results, IVIG cannot be recommended in tic disorders.

Edited July 14, 2016 by wisdom_seeker