Anti–basal ganglia antibodies are absent in patients with primary blepharospasm

Methodology and results.

Blood from seven consecutive patients (5 women, 2 men) with primary blepharospasm for a mean duration of 12.7 years (range 5 to 32 years) attending the botulinum toxin clinic at the National Hospital for Neurology and Neurosurgery, London, was collected for detection of anti–basal ganglia antibodies. Three of these patients (2 women, 1 man) had blepharospasm-predominant cranio-cervical dystonia, and two other women patients had an additional mild upper limb involvement apart from the blepharospasm. The rest (1 woman, 1 man) had blepharospasm alone. None of these patients were exposed to neuroleptics before the onset of their blepharospasm. Two patients, both women, were known to have other autoimmune disorders: one had biopsy- and antibody-proven celiac disease and Sjögren’s syndrome, and the other had pernicious anemia. All patients were receiving treatment with botulinum toxin for a mean duration of 8 years (range 2 to 12 years) at around 3-month intervals, with significant benefit. The presence of serum anti–basal ganglia antibodies was tested by Western Immunoblotting of homogenized human putamen, caudate, and globus pallidus.3 Antineuronal antibodies against human cerebellum, cortex, and myelin were also carried out as part of a routine paraneoplastic antineuronal antibody screen.

Basal ganglia-specific immunoglobulin (Ig) G antineuronal antibodies were not detected in any of the patients screened. All patients were also negative for antineuronal antibodies.

Discussion.

Studies indicate an enhanced excitability of the brainstem interneurons in patients with blepharospasm. Basal ganglia dysfunction is thought to be responsible for this enhanced brain stem excitability. Postmortem examination of patients with blepharospasm, either as a sole presentation or as part of Meige syndrome has demonstrated a range of changes from no abnormality to neuronal loss in the basal ganglia and brain stem nuclei. In a large study2 on 100 patients with blepharospasm and orofacial-cervical dystonia, Jankovic and Ford found 22% of their patients to have associated autoimmune disorders. Also, 26% of patients tested for antinuclear antibody were found to have titers more than 1:80. Subsequently, others4,5⇓ also reported this association and an argument was made for an autoimmune etiology to the pathogenesis of blepharospasm.

Basal ganglia antibodies are specific IgG antibodies that specifically bind to the cytoplasm of striatal neurons. These antibodies have been implicated in the pathophysiology of Sydenham chorea and pediatric autoimmune neuropsychiatric disorders associated with streptococcus that is phenotypically identical to Tourette syndrome. These antibodies have been shown to cause a basal ganglia dysfunction6 in rats.

Studies also indicate an association of blepharospasm, obsessive-compulsive symptoms, and Tourette syndrome. A common pathophysiologic mechanism between Tourette syndrome and cranio-cervical dystonia has been suspected.7 However, we did not detect anti–basal ganglia antibodies in any of our patients with blepharospasm-predominant cranio-cervical primary dystonia. Although the number of patients in this study is small, the absence of any basal ganglia-specific neuronal antibody in the serum of patients with primary blepharospasm suggests an alternative mechanism for basal ganglia dysfunction.