Background <p>Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a variant form of stiff person spectrum disorders. Paroxysmal respiratory failure and paroxysmal sympathetic hyperactivity syndrome (PSH) had rarely been reported in PERM cases.</p> Case presentation <p>We report a PERM case with acute onset of limb stiffness followed by rapid progression to severe sound-induced myoclonus with respiratory failure (oxygen saturation decreased to 30% with generalized cyanosis). The patient also exhibited ptosis, restricted rightward and downward eye movement, peripheral facial paralysis, and PSH. Anti-glycine receptor (GlyR) antibodies were detected in both serum and cerebrospinal fluid. Brain MRI was normal, while cervical MRI at the upper cervical segment showed linear lesions. The aforementioned symptoms significantly improved after intravenous methylprednisolone, intravenous immunoglobulin, plasma exchange, and other symptomatic treatments such as phenobarbital. We summarized the patient’s clinical presentations, cerebrospinal fluid and other laboratory test results, EEG, therapy, and 1-year follow-up. We also reviewed the literature and summarized the forms of onset of PERM, the presence of respiratory failure, and the effect on plasma exchange.</p> Conclusions <p>We describe a unique case of PERM characterized by acute onset, anti-GlyR antibodies positivity, PSH, and respiratory failure due to severe myoclonus. Early recognition and immunotherapy including plasma exchange may improve prognosis.</p>