Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare, severe variant of stiff person spectrum disorders characterized by rigidity, painful spasms, brainstem involvement, autonomic dysfunction, neuropsychiatric features, and hyperreflexia. It affects men more frequently and, if untreated, carries high mortality. Antibodies implicated include anti-GAD, glycine receptor (GlyR), NMDAR, and DPPX. About 20% of cases are paraneoplastic, most often associated with small cell lung cancer, lymphoma, melanoma, breast cancer, or thymoma. GlyR-positive PERM is typically the most treatment-responsive.

Presentation:
We describe a 30-year-old man who initially developed vertical diplopia, followed by progressive tremor, urinary retention with prostatitis, hallucinations, transient paresthesias, and episodic weakness. He subsequently developed bulbar weakness requiring intubation, tracheostomy, and PEG placement, complicated by autonomic instability. Initial investigations were unrevealing, including MRI, EMG/NCS, lumbar puncture, and infectious and autoimmune panels. He received IVIG with partial benefit. Three months later, he relapsed with worsening stiffness, diplopia, urinary retention, myoclonic jerks, and hallucinations. After failing pyridostigmine, he underwent plasma exchange with marked improvement. Antibody testing revealed GlyR and LRP4 positivity. He was started on Rituximab maintenance therapy with sustained clinical stability.

Discussion:
This case underscores the heterogeneity of PERM and the therapeutic responsiveness of GlyR-positive disease, particularly to plasma exchange and Rituximab. LRP4 antibody positivity has not previously been documented in PERM and may suggest an overlap with myasthenia gravis. Although no malignancy was identified, ongoing surveillance remains recommended given the paraneoplastic association. Reported treatment strategies include corticosteroids, IVIG, plasma exchange, and B-cell–depleting therapies, with thymectomy reserved for thymoma.

Conclusion:
PERM is a rare autoimmune disorder with diverse presentations, high morbidity, and mortality rates approaching 40%. Approximately one-third of patients present with stiffness and spasms, one-quarter with brainstem symptoms, and one-quarter require mechanical ventilation. Early recognition, antibody testing, and timely immunotherapy are critical for improving outcomes.