Case Presentation: A 59-year-old lady with history of paraplegia presented with acute onset of encephalopathy that started three days ago. On admission, she was repeating many words and not following any commands. Her neurologic exam was limited due to paraplegia of her lower extremities. In the hospital, infectious and metabolic causes were ruled out. CT of the brain did not show any abnormalities. She was unable to have a brain MRI due to a non-compatible pacemaker. EEG showed encephalopathy and lumbar puncture only showed an elevated protein of 225. CSF tests for infectious etiologies, including prion disease, came back negative. Her clinical status deteriorated with worsening rigidity and clonus of her upper extremities. Lorazepam was trialed for possible catatonia, although she had no response to it. She had comprehensive imaging, including a PET scan that showed no evidence of malignancy. Eventually, CSF testing for Anti-GAD 65 antibodies came back positive. Given acute encephalopathy, rapid worsening of her rigidity and clonus along with positive antibodies, she met criteria for Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM) syndrome. She was started on steroids and weekly rituximab therapy for 4 weeks with significant improvement in her mental status.
Discussion: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare neurological disorder that is suggested to be a more severe variant of the stiff-person syndrome (SPS). Symptoms usually include autonomic features, hyperekplexia (brainstem myoclonus or excessive startle), painful spasms and breathing problems. Glutamic acid decarboxylase (GAD), dipeptidyl-peptidase-like protein-6 (DPPX) antibodies and glycine receptor (GlyR) serum antibodies are commonly associated with this condition. The exact mechanism and triggering factors have not yet been identified. It is likely related to antibody-mediated pathogenesis with good response to immunotherapies. Our patient was diagnostically challenging, given her chronic paraplegia and the presence of a pacemaker. Common differentials include neurobrucellosis, NMDA encephalitis, paraneoplastic syndromes and neuroleptic malignant syndrome. Treatment options include IVIG, plasmapheresis, immunosuppressive drugs along with intrathecal baclofen. Clinical recovery can occur over many months and long-term prognosis is unclear.
Conclusions: PERM should be included in the workup of patients presenting with acute encephalopathy as well as seizures with prolonged encephalopathy. Although this condition is uncommon, hospitalists must be aware of this condition and consider this entity in the differential to make the proper diagnosis to reduce morbidity and mortality.