Paroxysmal cold-induced unilateral leg stiffness as the initial manifestation of suspected stiff-person syndrome

Abstract Background Stiff person syndrome is a rare autoimmune neurologic disorder characterized by rigidity and stimulus-sensitive spasms. Focal presentations may be diagnostically challenging, particularly when early imaging and electrodiagnostic studies are unrevealing. Case presentation We report the case of a 44-year-old Armenian-Hungarian woman who developed an approximately 7-week history of episodic left leg stiffness provoked by walking and external stimuli. A cold breeze reproducibly precipitated abrupt stiffening with transient inability to advance the leg. The episodes became more frequent and prolonged, causing gait instability, falls, and cane dependence. Brain and lumbosacral magnetic resonance imaging and early nerve conduction and electromyographic studies were unrevealing. Serum glutamic acid decarboxylase 65 antibody was 23,898 U/mL (reference < 0.5 U/mL; Esoterix, Inc.), supporting a clinically suspected focal stiff person spectrum disorder without electrophysiological confirmation. Intravenous immunoglobulin was administered at 2 g/kg over 2 days monthly for 3 months, followed by 1 g/kg monthly for 6 months. Treatment was followed by less stiffness, improved gait, fewer falls, and improvement in cold-triggered episodes; these outcomes were assessed qualitatively. Conclusions Paroxysmal cold-triggered unilateral leg stiffness may prompt consideration of a focal stiff person spectrum disorder. A normal routine electromyogram does not exclude the diagnosis, but the absence of electrophysiological confirmation requires cautious interpretation of the clinical and antibody findings and careful assessment of alternative diagnoses.