Intravenous immunoglobulins do not improve tics in a patient with Gilles de la Tourette syndrome and intrathecal antibody synthesis
Creators: name: Fremer, Carolin
name: Szejko, Natalia
name: Sühs, Wolfram
name: Müller-Vahl, Kirsten
Publisher: name: F1000 Research Limited
Year: 2019

description: Background:<br>Numerous findings support an involvement of the immune system in the pathophysiology of Gilles de la Tourette syndrome (GTS). For example, positive oligoclonal bands (OCB) in cerebral spinal fluid (CSF) occur in 20-30% of adult patients with GTS indicating an intrathecal antibody synthesis. However, until today no corresponding antibodies could be identified. While from uncontrolled studies in a small number of patients it has been suggested that treatment with intravenous immunoglobulins (IVIG) may improve tics, a double-blind placebo-controlled study in 30 unselected patients failed to demonstrate efficacy.<br>Here we present the case of a female patient with GTS with positive OCBs, in whom an immunoneuropathy was treated with IVIG. Based on the hypothesis that positive OCBs might serve as a biomarker, we were interested in whether her tics improved after treatment.<br><br>Case description:<br> For the first time, the patient presented in our Tourette clinic at the age of 40. Further clinical exploration revealed the diagnoses of obsessive-compulsive disorder (OCD), self-injurious behavior, sleeping problems, as well as a history of a depressive episode and abuse of alcohol and benzodiazepines. Treatments with antipsychotics and habit reversal training did not result in a significant improvement of tics or intolerable side effects. At age 44, the patient participated in our clinic in a study to investigate CSF parameters in GTS. In this patient, CSF isolated OCBs (Type 2) were identified, while all other immunological investigations were negative.<br>At age 46, she presented with tetraparesis mostly affecting the left limbs, distal hypesthesia and paresthesia, and dyspnea. Three months before, similar symptoms had occurred and CSF pleocytosis was detected in an external clinic. Antibiotic treatment resulted in a complete remission. During hospitalization in our clinic, further examination demonstrated normal results in EMG, MRI, CSF, virological and bacteriological tests, as well as autoimmune antibodies. Based on the clinical presentation the diagnosis of immunoneuropathy was made and treatment with IVIG (30g/day) was initiated (for 5 days) resulting in a complete remission. A relapse 3 months later again responded to treatment with IVIG (30 g/day for 5 days).<br>Because OCBs were positive already before clinical symptoms of an immunoneuropathy manifested, we assessed tics, premonitory urges, and psychiatric comorbidities (including OCD, attention deficit hyperactivity disorder (ADHD), depression, and anxiety disorder) before and several times after treatment with IVIG. However, while the patient recovered from immunoneuropathy, tics and premonitory urges slightly improved only at 2 weeks after initiation of IVIG treatment and went back to baseline level after 5 weeks.<br><br>Conclusions:<br>We hypothesized that positive CSF OCBs could serve as a biomarker for successful treatment of tics, premonitory urges, and psychiatric comorbidities using IVIG in a patient with GTS. However, while the patient’s immunoneuropathy resolved, tics and comorbidities remained unchanged. Slight improvement of tics after 2 weeks should be interpreted in the context of recovery from immunoneuropathy and improved quality of life. In summary, from this case it is not suggested that IVIG is effective in the treatment of GTS even in patients with intrathecal antibody synthesis.