11C-Flumazenil positron emission tomography demonstrates reduction of both global and local cerebral benzodiazepine receptor binding in a patient with Stiff Person Syndrome

Stiff-person syndrome: insights into a complex autoimmune disorder

“…A lack of facilitation of H-reflexes in this study argued against spinal mechanisms as being responsible for the MEP changes 78. Furthermore, a global decrease in the benzodiazepine receptor binding in the brains of three patients with SPS assessed by [ 11 C]flumazenil positron emission tomography has been documented, with significant clusters in the premotor and motor cortex 79 80. This latter finding suggests an altered postsynaptic cortical-inhibitory mechanism as the benzodiazepine receptors colocalise with the GABA A receptors.…”

GAB Aergic Changes in 11C-Flumazenil PET in the Drug-Naïve Stiff-Person Syndrome

“…Most patients in previous studies had taken medications that may have affected 11 C-FMZ Pet findings. [2][3] A hypothetical mechanism for reduction of FMZ binding might be the autoimmunity to GAbA A -receptor-associated protein (GAbARAP) in stiff-person syndrome. Recently, Raju et al suggested the possibilities that GAbARAP may be an autoantigen of pathogenic significance in SPS, and in that study, a significant decrease was found in the level of GAbARAP in patients with anti-GAD antibody positive SPS, and about 70% of the patients showed significantly high anti-GAbARAP antibodies correlating with clinical severity.…”

“…1 the pathophysiology of SPS remains elusive, but laboratory and functional neuroimaging studies suggest that γ-aminobutyric acid (GAbA)ergic dysfunction plays a major role in its pathogenesis. [1][2][3][4] Positron emission tomography (Pet) studies using the benzodiazepine antagonist 11 C-flumazenil (FMZ) showed significant reduction of FMZ binding in brains of patients with SPS, which implied the decrease of the postsynaptic GAbA A receptor availability in the brains of SPS patients. [2][3] Magnetic resonance spectroscopy (MRS) demonstrated significant reduction of brain GAbA levels in patients with SPS.…”

“…[1][2][3][4] Positron emission tomography (Pet) studies using the benzodiazepine antagonist 11 C-flumazenil (FMZ) showed significant reduction of FMZ binding in brains of patients with SPS, which implied the decrease of the postsynaptic GAbA A receptor availability in the brains of SPS patients. [2][3] Magnetic resonance spectroscopy (MRS) demonstrated significant reduction of brain GAbA levels in patients with SPS. MRS results suggested a correlation between reductions in GAbA levels and SPS severity, but this was not investigated using 11 C-FMZ Pet.…”