Stiff-person syndrome and generalized anxiety disorder.

Master Degree Student, Laboratory of Panic & Respiration, Institute of Psychiatry, Federal University of Rio de Janeiro, INCT Translational Medicine, Rio de Janeiro RJ, Brazil; Assistant Professor, Neurology Service, State of Rio de Janeiro University, Rio de Janeiro RJ, Brazil; Assistant Professor, Federal University of State of Rio de Janeiro, Rio de Janeiro RJ, Brazil; Associate Professor. Laboratory of Panic & Respiration, Institute of Psychiatry, Federal University of Rio de Janeiro, INCT Translational Medicine, Rio de Janeiro RJ, Brazil. Stiff-person syndrome (SPS) also called stiff-man syndrome, is an immune-mediated CNS disorder characterized by progressive rigidity of the trunk and proximal limb muscles, associated with intermittent superimposed spasms and heightened sensitivity to external stimuli. The spasms are often triggered by emotions, such fear and unexpected tactile, auditory or emotional stimulation. In most cases, SPS is associated with high levels of serum and cerebrospinal fluid autoantibodies against glutamic acid decarboxylase (GAD-65), the ratelimiting enzyme for the synthesis of a major inhibitory neurotransmitter, gammaamino-butyric acid (GABA). The autoantibodies to GAD65, which are also produced intrathecally, can inhibit the activity of GAD65, thus impairing the synthesis of GABA, and resulting in low GABA levels in the brain and CSF. The reduction of brain GABA in patients with SPS supports the clinical symptoms and indicates that the inhibitory GABAergic pathways are involved in the disease. The association between SPS and anxiety disorders has been reported. Anticipatory anxiety is common in SPS patients, occurring in situations perceived as physically unsafe, such as crossing a busy street or walking unaided in open spaces. These situations may precipitate attacks of increasing stiffness or spasms that result in falls. Generalized anxiety disorder (GAD), panic disorder, post-traumatic stress disorder and phobic disorders have been described in patients with SPS. The pathogenesis of anxiety disorders in patients with SPS remains unknown. However, there is considerable evidence that dysfunction of GABA concentrations in central nervous system (CNS) plays an important role in the pathophysiology in these two conditions. We report a patient with typical features of SPS and antibodies to glutamic acid decarboxylase, who also met the criteria for generalized anxiety disorder. The possible relationship between these two conditions is discussed.